Research Studies

Research Studies on Complementary and Alternative (CAM) Therapies and Children with Cancer

 

Although there is increasing work being done in the area of cancer and complementary therapies, currently, there are few research studies specifically being conducted in pediatric oncology. Studies now in progress or in various stages of completion in the Division of Pediatric Oncology, Columbia University are as follows:

A Pilot Study to Evaluate the use of Citrulline as a Reliable Quantitative Biomarker of Small Bowel Enterocyte Mass, Intestinal Integrity, and Intestinal Mucosal Damage After Allogenic Hematopoietic Stem Cell Transplantation (HSCT)

Status: Recruting Patients

Study Purpose and Rationale

Myeloablative regimens are the backbone of hematopoietic stem cell transplantation (HSCT) and are associated with prolonged periods of cachexia/anorexia, nausea/vomiting, mucositis, and compromised gut integrity (CGI). CGI makes nutrition interventions challenging, decreases oral tolerance to foods, reduces quality of life and functional status, delays the transition from the hospital to home setting, and increases the risk of the development of a gut-derived infections. Currently, morphologic parameters and sugar permeability tests are the objective endpoints used in preclinical and clinical studies to measure CGI; however, both methods are unsuited for monitoring purposes in routine clinical practice.  There is a need for a reliable blood marker of CGI.  Plasma citrulline reflects the integrity of the intestinal epithelial cells and is an indicator of the functional enterocyte metabolic mass.   Adult studies that have demonstrated that serum citrulline levels can be used to monitor small bowel toxicity following myeloablative therapy. We are proposing a pilot study evaluating the use of serum citrulline as a quantitative marker of intestinal toxicity and overall intestinal health before and after pediatric allogenic HSCT.

Study Subjects

All patients undergoing myeloablative allogeneic (matched, unrelated or sibling matched) at CHONY will be eligible. The source of stem cells can be from bone marrow, umbilical cord blood or cytokine mobilized peripheral blood.  Donor can be HLA matched, sibling, or parent, a related donor mismatched for a  single HLA locus (class I or II), unrelated marrow or peripheral blood stem cell donor, or unrelated cord blood at least 4/6 antigen match (Class I or II). Eligible patients are of either gender and between 2 and 21 years of age.

Study Procedures

We are proposing a pilot study evaluating the use of serum citrulline as a quantitative marker of intestinal toxicity and overall intestinal health after pediatric allogenic HSCT. Patients will have citrulline levels drawn on the following days: Day 1 of conditioning therapy, 0, +3, +7, +14, and +21. All timepoints will be collected +/- 1 day of the designated timepoint.  Clinical parameters will be monitored to determine oral mucositis scores and intestinal toxicity/GVHD scores on all patients.

We are expecting to recruit 10 pediatric patients who will undergo a myeloablative HSCT. Demographic data will be collected at baseline and will include: age, sex, race/ethnicity. Clinical data collected during the study period will be diagnosis, conditioning regimen, incidence and duration of bacteremia, frequency of emesis and diarrhea, incidence and severity of abdominal pain, engraftment data, incidence and grade of oral mucositis, incidence of acute graft versus host disease, incidence of clostridium difficile, incidence of other infectious diarrhea, and typhlitis.

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

back to top

A Limited Institution Pilot Trial Evaluating the Safety of Administering the Probiotic, Lactobacillus plantarum, to Children and Adolescents Undergoing Allogeneic Hematopoietic Stem Cell Transplantation (HSCT)

Status: Recruting Patients

Study Purpose and Rationale

Myeloablative regimens are the backbone of hematopoietic stem cell transplantation (HSCT) and are associated with prolonged periods of cachexia/anorexia, ausea/vomiting, mucositis, and compromised gut integrity (CGI). The toxicities associated with HSCT often lead to prolonged periods of poor oral intake and may result in overt malnutrition. CGI decreases oral tolerance to foods, reduces QOL and functional status, delays the transition from the hospital to home setting, and increases the risk of the development of gutderived infections. Probiotics are nutritional supplements that contain a defined amount of viable microorganisms and upon administration confer a benefit to the host. Clinical trials in adults receiving organ transplants have found probiotics decrease the incidence of infection, the duration of antibiotic use, the incidence of multiorgan failure and systemic inflammation. Children and adolescents undergoing HSCT, experience similar clinical challenges suggesting probiotics may have a therapeutic value in the setting of HSCT. We are proposing to evaluate the safety and feasibility of administering probiotics to children and adolescents undergoing HSCT.

Study Subjects

All patients undergoing myeloablative allogeneic HSCT will be eligible.  The source of stem cells can be from bone marrow, umbilical cord blood or cytokine mobilized peripheral blood. Donor can be HLA matched sibling or parent, a related donor mismatched for a single HLA locus (class I or II), unrelated marrow or peripheral blood stem cell donor, or unrelated cord blood at least 4/6 antigen match (Class 1 or II). Eligible patients are of either gender, between 2 and 17.99 years of age, and may be receiving any type of GVHD prophylaxis.

Study Procedures

This pilot study will evaluate the safety of probiotics administered to children undergoing allogeneic HSCT.  Patients will all receive supplementation with L. plantarum 299and 299v  for a total of 22 days beginning seven days prior to HSCT (Day –7) and continuing for two weeks post HSCT (day + 14) (Figure 1).  Patients will receive a daily dose of Lactobacillus plantarum:  1 x108 CFU/kg/day. This supplement will be supplied in sachets of powder and will be mixed in water (certain water-based liquid) that is no warmer that 37o C.

We will study 30 patients who will undergo a myeloablative HSCT.  Demographic data will be collected at baseline and will include: age, sex, and race/ethnicity.  Clinical data collected during the study period will be diagnosis, conditioning regimen, incidence and duration of infections, engraftment data, incidence of acute graft versus host disease, incidence of bacteremia and gastrointestinal tract infections include Clostridium difficile infection, typhlitis, and enterocolitis and incidence of L plantarum bacteremia.  

Compliance to the recommended regimen will be measured by examination of the medication administration record or other hospital source documentation verifying that the daily dose was administered.  

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

back to top

A Prospective Study Evaluating the Role of Dietary Intake and Nutritional Status on Neuropathy, Functional Measures of Quality of Life, and Fatigue in Children Receiving Treatment for a Brain Tumor

Status: Recruting Patients

Study Purpose and Rationale

Children with brain tumors consistently have difficulty maintaining dietary intake and nutritional status throughout surgery, radiation, and chemotherapy, although the causes, timing, and duration of compromised nutrition status have not been well described. Weight loss is typically severe (> 5-10% body weight) and cumulative and may contribute to toxicities, and yet there are no consistent clinical guidelines for intervention. Nutrition interventions are time consuming and require utmost compliance from patients and families. Targeting specific interventions for defined periods of time may provide the most effective and efficient interventions to restore function and reduce morbidity.

We hypothesize that poor quality dietary intake and low nutritional status increases the incidence and risk for peripheral neuropathies, compromises energy levels, and reduces functional quality of life. The primary purpose of this longitudinal study is to determine the role of B vitamins on the incidence and severity of neuropathy in children receiving treatment for a brain tumor.

Study Subjects

Patients with a diagnosis of medulloblastoma/PNET, ependymoma and low grade glioma and who are between the ages of 3-21 are eligible to participate.

Study Procedures

Patients will be identified through a designated investigator at each institution.  Upon identification of an eligible participant, physician consent will be obtained and a study investigator will inform parents/patients about the study and inquire about participation.  If the parent/patient consents/assents, the appropriate forms will be signed.  A sample of 144 children with a brain tumor will be entered into the study and will complete assessments on dietary intake, functional assessment of quality of life, and fatigue at the beginning and mid point each treatment intervention phase of therapy.  Assessments on nutrition status and neuropathy will be completed by a designated member at each site. Dietary questionnaires may be self-administered during a routine clinic visit or by scheduling an appointment, per the parents’/patients’ preference. 

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

back to top

Survey of the Use of Traditional and Complementary/Alternative Medicine (TCAM) in Children with Cancer in an Urban Medical Center in Guatemala

Status: Recruiting Patients

Study Purpose and Rationale

Perceptions of disease and illness and TCAM practices among Guatemalan children diagnosed with cancer and their families and its consequent impact on the decision for and continuation of cancer treatment have yet to be explored. The role of TCAM among children with cancer in Guatemala is unknown. It is unclear how many children living with cancer in Guatemala go undiagnosed and whether these children are using TCAM in lieu of conventional medicine. It is also unknown whether children diagnosed with cancer in Guatemala are using TCAM. It is hypothesized that the advanced presenting stages of children diagnosed with cancer in Guatemala may in part be related to TCAM use. To date, this has not been thoroughly investigated.

We are proposing to conduct a cross-sectional survey to document the use of TCAM and describe associations of TCAM use in children diagnosed with cancer and being treated at UNOP (Unidad Nacional de Oncologia Pediatrica, Guatemala). Collaborators for this project include the UNOP, Guatemala; St. Jude Children’s Hospital, and the Division of Pediatric Oncology, Columbia University. We plan to survey a cross-sectional sample of patients who are newly diagnosed, have completed treatment or who have relapsed or have progressive disease and are being followed by the health care team at UNOP, Guatemala.

The information gathered from the proposed survey will assist in identifying rates of TCAM use, the specific TCAM therapies commonly used, and the reasons for TCAM use among Guatemalan children diagnosed with cancer at UNOP.

Study Subjects

All patients with a diagnosis of cancer and are cared for at the Unidad Nacional de Oncologia Pediatrica, Guatemala will be eligible for the study. Three groups of patients will be surveyed, (1) patients who are receiving conventional therapy (chemotherapy, radiation therapy, and/or surgery), (2) children who have completed treatment and are in the follow up phase, and (3) children who have relapsed or have progressive disease and are receiving palliative care.

Study Procedures

A random sample of families of children with cancer will be identified. The staff physicians, nurses or psychologist of UNOP will approach the patient and parent/guardian about participation during a routine visit. Upon patient consent by the parent/guardian and patient assent (age 7 years), a face-to-face interview will be completed.

Contact Information:

Kara M Kelly, MD
Division of Pediatric Oncology
Columbia University
161 Fort Washington Avenue, AP-7
New York, NY 10032
kk291@columbia.edu

This study is currently being expanded to investigate and explore the use of TCAM among children with cancer in Costa Rica, Argentina, Philippines, Qatar, and Israel.

back to top

A Prospective Study of the Variables Associated with the Acceptance of Acupuncture Among Children With Cancer

Status: Recruiting patients

Study Purpose and Rationale

The Integrative Therapies Program for Children with Cancer (ITPCC) was initiated in 1998 to begin investigating the safety of CAM therapies and provide a reliable resource for children treated in The Division of Pediatric Oncology at Columbia University. This program provides clinical services and educational resources to children undergoing treatment for cancer and conducts research investigating the safety, feasibility, and efficacy of many CAM modalities.  Since the program’s inception, eight CAM trials have been initiated. Many of the results obtained from the program’s pilot studies are being investigated through two leading international pediatric oncology consortiums, Children’s Oncology Group and The Dana Farber Cancer Institute ALL Consortium.

The ITPCC has conducted studies investigating the acceptance of acupuncture among children and adolescents with cancer treated at The Herbert Irving Child & Adolescent Cancer Center. In a retrospective review of patients receiving acupuncture services over a 6-month period, 172 acupuncture treatments were delivered to 25 children and adolescents with cancer. The mean number of treatments per patient was 6.9 (range 1-32), which demonstrated a high acceptance among children and adolescents with cancer. Acupuncture was found both feasible and well accepted among children at various ages (age range 1-22 years old) and with diverse malignancies.   

A second retrospective review investigated the incidence of adverse events related to acupuncture in children with and without thrombocytopenia.  The records of 32 patients between the ages of 2 and 22 years were reviewed over a one-year period, during which 237 sessions of acupuncture were administered in the inpatient and outpatient settings. 20% of patients received acupuncture with severe thrombocytopenia (platelet counts ≤20,000/µL), 8% of patients received acupuncture with moderate thrombocytopenia (platelet 21,000-50,000/µL) and 72% of patients received acupuncture with mild thrombocytopenia (>50,000/µL). 49 acupuncture sessions (20.6%) were associated with the administration of low molecular weight heparin and 45 sessions (18.9%) were associated with the use of corticosteroids on the same day of acupuncture treatment; no patients had a blood urea nitrogen value >50mg/dl.  Despite the high number of sessions administered in patients with thrombocytopenia and other risk factors for bleeding, neither bleeding nor bruising complications were observed.  Of the 237 sessions, one hematoma was observed, however it was unclear if it was associated with acupuncture treatment.  This review suggests that acupuncture may be considered in children undergoing treatment for cancer with thrombocytopenia.  The proposed study will further explore this initial observation. 

We are proposing a prospective study to investigate variables (demographics and therapy-related side effects) associated with the acceptance of acupuncture among children and adolescents with cancer.  We hypothesize that the expected side effects associated with treatment for cancer may be related to patients’ acceptance of acupuncture.  The data collected from this study will guide future research initiatives and assist in the development of a model for providing acupuncture to children and adolescents with cancer in a conventional medical center.

Study Subjects and Method of Recruitment

Acupuncture is an optional, complimentary, clinical service provided to all children and adolescents treated in the Division of Pediatric Oncology.  Acupuncture is routinely offered to patients as an adjunct to their standard clinical care.  All patients treated at the Herbert Irving Child & Adolescent Cancer Center and are acupuncture-naïve (never received acupuncture) will be eligible for participation in the study.

Prior to the routine patient introduction to the services of the ITPCC, the patient’s primary physician will be consulted about the patient’s participation in the study.  Upon physician approval, acupuncture-naïve patients treated in the Division of Pediatric Oncology will be informed about the services of the ITPCC and offered participation in the study.  If the patient consents, the patient will enter the study for a 6 month period.   

Study Procedures

Individualized acupuncture treatments will be administered to the patient based on the primary complaint and will follow the guidelines of the ITPCC. Acupuncture treatments may be provided during a patient’s regularly scheduled visit, in the inpatient or outpatient setting.  Travel to another facility is not necessary. Only licensed acupuncturists (L.Ac.) employed by the ITPCC will provide acupuncture treatments.

Patients will complete two questionnaires at baseline, a demographic datasheet and a symptom checklist. The symptom checklist will be administered directly to patients (≥10) or to the parent(s) or guardian (patients < 10) at baseline, at each 2-week observation time point and prior to acupuncture treatments. A brief pre/post acupuncture treatment questionnaire evaluating acupuncture acceptance and perceptions of acupuncture prior to and following the each acupuncture session will be administered either to the patient (≥10) or to the patient’s parent(s) or guardian (patients < 10). The pre/post acupuncture questionnaires will be administered only to patients accepting treatment with acupuncture. Demographic variables such as age, gender, and socioeconomic status, diagnosis, type of protocol, cycle of cancer therapy, concomitant medications, results of routine laboratory tests and side effects will be recorded and collected from the patient’s medical chart.  The analysis will be descriptive in nature.

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu
back to top

A Pilot Study Investigating the Effects of Glutamine and Vincristine-induced Neuropathy in Pediatric Patients with Cancer

Status: Recruiting Patients

Study Purpose

Children treated with anticancer protocols may experience a number of toxicities which may necessitate a reduction of chemotherapy or delays in their treatment protocols. Vincristine (VCR) is a vinca alkaloid derived from the periwinkle plant and is used in the treatment of hematological malignancies and solid tumors. VCR has a broad spectrum of activity and has evolved as an integral component of many protocols treating children diagnosed with acute lymphoblastic leukemia, neuroblastoma, Ewing’s sarcoma, Wilm’s tumor, rhabdomyosarcoma, Hodgkin’s disease and non-Hodgkin’s lymphoma. However, VCR has also been found to interfere with a number of other biochemical and biological activities. The nutritional supplement, glutamine, is classified as a nutritional supplement in that it is currently not an established supportive care agent in use with conventional chemotherapy protocols. The low toxicity and possible plausibility of glutamine suggests it may be of benefit for children undergoing anticancer protocols. Glutamine should not interfere with cancer control and may ameliorate the neurotoxic effect of VCR.

We are conducting a double-blind, randomized, placebo-controlled trial to investigate the efficacy of glutamine in the treatment of vincristine-induced neuropathy in children with cancer. This study will also provide descriptive data on the incidence of VCR-induced neuropathy. Despite a number of investigations and reviews describing the well-known dose-limiting neuropathy associated with VCR administration, VCR-induced neuropathy remains largely undocumented in the pediatric oncology population. Physicians estimate approximately 30-50% of their patient population requires dose reductions or holds in their VCR therapy depending on the patient’s protocol. This study will be the first to document the incidence of VCR-related neuropathy in the pediatric oncology population.

Study Subjects and Method of Recruitment

All patients between the age of 5 and 21 who are being treated with protocols which include at least 10 or more planned doses of VCR within a 30 week time-frame will be eligible. Given this criteria, patients diagnosed with acute lymphoblastic leukemia, non-Hodgkin’s lymphoma, Hodgkin’s disease, Ewings sarcoma, Wilms tumor, and rhabdomyosarcoma will be eligible for participation in the study. Prior to the initiation of an intensive vincristine-containing course, patients will be approached by the study coordinator to inquire about participation in the study. If the parent or guardian consents and the patient assents (age > 7yrs) to participation, baseline data on the subject’s neurological status will be collected prior to the initiation of intensive vincristine-containing therapy. A blood specimen will also be collected to obtain baseline data on serum markers of neurological status. Subjects’ neurological status will be monitored in a monthly basis by the pediatric oncology psychologist and during the subjects'’ routine clinical exam. Upon identification of clinically mild neuropathy, subjects will be eligible for randomization.

Study Procedures

Subjects will be randomized by the institution’s pharmacy to receive the study drug, glutamine, or placebo, for 21 days after administration of their VCR therapy. Supplementation with glutamine will begin the following day of their VCR therapy. Subjects will be followed for a 42-day period. After the initial 21-day supplementation period, data will be collected on subject’s neurological status and compared to the pre-supplementation period. Data will also be obtained on neuropsychological exams. Subjects will then be followed for an additional 21-day period. At the end of this period, assessments from both clinical and neuropsychological examinations will be collected. Subjects will also be asked to donate three blood specimens during the intervention period.

Contact Information

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

Refer to our Manuscripts for more information.

back to top

Survey of the Use of Complementary/ Alternative Medicine (CAM) in Survivors of Childhood Cancer in an Urban Medical Center

Status: Data analysis, study closed to recruitment.

Study Purpose

Surveys have found that the use of complementary/alternative medicine (CAM) is highly prevalent among children undergoing therapy for pediatric malignancies. A survey at Columbia University, Division of Pediatric Oncology found 84% of patients use some form of CAM during cancer therapy. The incidence of late-effects of cancer therapy is high among pediatric survivors of cancer. Studies have found that 60-70% of survivors of childhood and adolescent cancers will have at least one late-effect from anticancer therapy. It is possible that survivors of childhood cancer may use CAM to prevent or lessen the long-term side-effects of chemotherapy and radiation therapy. To date, this has not been thoroughly investigated.

We are proposing to conduct a survey to document the incidence of the use of CAM in survivors of childhood cancer. We plan to survey a cross-sectional sample of patients who are survivors of childhood cancer and are being followed by their primary oncologist located at the Herbert Irving Child & Adolescent Cancer Center. We also plan to conduct a longitudinal follow-up study on a cohort of patients who participated in our original survey documenting the incidence of CAM in children receiving anticancer therapy. The information gathered from the proposed survey will assist in identifying the prevalence of the use of CAM among childhood cancer survivors, assist in identifying specific therapies that are commonly used among survivors, and identify differences in the use of CAM in survivors compared to children receiving active treatment for their cancer. The information collected will aid in providing information to the survivor population as well as direct future research priorities.

Study Subjects and Method of Recruitment

Both English and Spanish speaking children who have completed the planned cancer therapy and have been off-therapy for at least three months will be eligible for participation in the study. The child’s primary oncologist will contact subjects either during a routine follow-up visit or by a letter. A letter describing the investigation will be mailed by the child’s primary oncologist and will explain the survey for those patients participating in the longitudinal follow-up study. The letter will be followed up with a telephone call by the child’s primary oncologist or research assistant. Upon patient consent by the parent/guardian and patient consent (age > 7 years), a phone interview or face-to-face interview will be scheduled.

Study Procedures

The research assistant will schedule an interview to be done face-to-face during a routine follow-up visit or over the telephone. Each interview will last approximately 30 minutes. The questionnaire will cover demographic variables, use of CAM, visits to alternative medicine practitioners, cost (out of pocket or third party), and whether patients or parents/guardians report the use of CAM to their physicians. Clinical information including type of cancer, treatment received and any late-effects encountered will be obtained from patient charts.

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Fort Washington, IP-7
New York, NY 10032
ejd14@columbia.edu

Refer to our Manuscripts for more information.

back to top

A Pilot Study of Silymarin during Maintenance Therapy in Children with Acute Lymphoblastic Leukemia (ALL) and Abnormal Liver Function Tests

Status: Data analysis, study closed to recruitment.

Study Purpose

Patients with cancer are amongst the highest users of complementary/alternative therapies. A recent survey found 85% of pediatric patients on standard Children's Cancer Group protocols are taking some form of complementary/alternative medicine. Yet the safety of these therapies combined with chemotherapy is unknown. Acute lymphoblastic leukemia (ALL) is the most common childhood cancer afflicting nearly 1/3 of all pediatric cancer patients. The 5-yr prognosis has escalated in the past few decades from 5% in the 1960's to nearly 80% in the year 2000. Yet, this therapy is not without toxicity. About 25% of ALL patients treated with chemotherapy during the maintenance phase of their therapy will encounter liver toxicity. Currently, there are no other less toxic chemotherapy drugs that are as effective; therefore, the child may need a decrease in the recommended dose of chemotherapy or be delayed in his/her therapy. This might increase a child's risk of relapse. Milk thistle is an herb that is widely used in Europe for the treatment of liver disorders. The herb can be administered at high doses without adverse effects. There are numerous trials in adults and some literature in children supporting its use with liver disorders. This has not been studied in patients with cancer. We are proposing to conduct a double-blind, placebo controlled randomized trial to determine the efficacy of milk thistle supplementation in children with liver toxicity from chemotherapy during the maintenance phase of their therapy. Patients will be randomized to receive either a placebo (inactive substance) or the active herb, milk thistle. Patients will take the herb for a one-month period. Measures of liver function will be assessed throughout the study at their routine visits. Patients will be routinely monitored for any adverse effects. Our hypothesis is that milk thistle supplementation in pediatric patients with ALL with result in resolution of liver toxicity.

Study Subjects and Method of Recruitment

This study was a collaborative effort with the Children's Hospital of Philadelphia. We proposed to recruit 50 children with ALL who are incurring liver toxicity from chemotherapy. The maintenance phase of chemotherapy for children being treated per the CCG or COG protocol includes every 28-day outpatient appointments for intravenous chemotherapy. A course consists of 84 days (three cycles) and is identical across various risk-based protocols. Per protocol, the patient has evaluations of their hepatic function on Day 0. If a patient meets any of the above criteria on a single blood draw they were eligible to participate in this study. The institution's principal investigator approached the parent or guardian to ask about participation in the study. If the parent or guardian consented and the patient assented (age > 7 yrs), to participation, the patient was randomized by the institution's pharmacy to receive the study drug, silymarin, or placebo, daily for the next 28 days. Supplementation began the following day. In an effort to check compliance, patients were asked to return their bottle of supplements and the number of unused capsules were tabulated.

Study Procedures

Patients routinely have clinic appointments every 28 days for chemotherapy and lab analyses. At Day 0, patients have their liver function checked per protocol. If the patient is eligible and consents, an extra 21 ml of blood will be withdrawn on Day 0, Day 28 and Day 56 for antioxidant analyses, liver function (liver function is not a required observation on Days 28 and 56 on the chemotherapy protocol), DNA damage (measured by 8-oxodeoxyguanosine) and plasma free and conjugated serum silibinin values. The current proposal does not require additional clinic visits by patients.

Blood specimens from all three time points will be sent to the in-house laboratory for liver function analyses. For measurements of antioxidant status and oxidative damage, blood specimens will be collected in heparin tubes and will be sent by overnight delivery to Dr.Regina Santella's Laboratory for processing and storage until all specimens are collected. Upon completion of the study, 150 specimens (50 from Time 0, 50 from Time 1, and 50 from Time 2) will be packed on dry ice and send by overnight delivery to Tufts University for ORAC analyses. The levels of 8-oxodeoxyguanosine adducts will be completed by Dr. Santella's laboratory for each of the three time-points. To control for dietary intake, a food frequency questionnaire and 24hr recall will be administered to patients at each time of blood withdrawal.

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

Refer to our Manuscripts for more information.

back to top

A Pilot Study of Aromatherapy to Reduce Anxiety and Nausea in Children Undergoing Stem Cell and Bone Marrow Transplants

Status: Data analysis; study closed to recruitment.

Study Purpose

Patients with hematological malignancies and some with solid tumors often undergo stem cell or bone marrow transplants during the course of their treatment. Transplantation is preceded by high-dose chemotherapy and radiation in order to prepare the patients' marrow to receive the transplanted cells. The side effects of these conditioning regimens may be severe, including nausea, vomiting, and oral pain due to mucositis; and there is often a great amount of anxiety in patients and their parents regarding the transplant process itself. Infusion of stem cells or marrow preserved in foul-smelling DMSO can also cause considerable nausea and discomfort in these patients. For children in particular, these symptoms represent additional stressors in an already traumatic period in their lives, the effects of which can last far beyond the transplant period. Studies have shown that children who undergo such transplants are at increased risk for long-term social, emotional, and behavioral problems.

One of the complementary therapies increasingly used to reduce the distress associated with hospitalization and various medical treatments is aromatherapy. Aromatherapy is defined as the therapeutic use of essential oils for the improvement of physical, emotional, and spiritual well being. The essential oils used by aromatherapists are pleasant-smelling distillates of specific aromatic plants, which may be used in conjunction with massage or simply inhaled and absorbed through the nasal mucosa. Specific essential oils are touted as having sedative, stimulant, antiemetic, and other properties; however, very little research has been done to prove these claims. Those few studies which might stand up to scientific scrutiny have been contradictory in their results. However, aromatherapy has gained in popularity over the past decade, and has been utilized in many settings to increase patients' sense of well being and to combat specific symptoms related to their disease or treatment. At the Children's Hospital of New York, aromatherapy has recently been used in the setting of stem cell and bone marrow transplantation, in order to relieve the anxiety and nausea associated with the infusions. However, its use in this setting has never been tested.

Patients and Methods

We are proposing to recruit 40 children between the ages of 5 and 21 years who are scheduled to undergo stem cell or bone marrow transplantation. The parents of these patients will also take part in the study. All patients will be recruited from CHNY. The institution's principal investigator will approach the parent or guardian to ask about participation in the study. If the parent or guardian consents and the patient assents (age > 7 yrs) to participation, the patient and his or her parent will be given age-appropriate questionnaires, which will measure baseline temperament, coping styles and anxiety levels. On the day of transplantation, the patient will be randomized to receive either aromatherapy or placebo (scented shampoo) via diffuser during the course of transplantation.

Study Procedures

Upon recruitment into the study, patients and their parents will be evaluated for baseline anxiety levels using the Spielberger State-Trait Anxiety Inventory (STAI). Children will fill out another questionnaire assessing coping skills. Parents will also fill out questionnaires assessing their child's temperament and their own coping skills. On the day of transplantation, the STAI questionnaire will be administered to both parent and child prior to the start of the infusion, at the end of the infusion, and once more at the end of the hour following infusion. Visual analogue scales for nausea and pain will also be administered to the patient at these times. After the first set of questionnaires is given, the aromatherapy diffuser will be filled with four drops of essential oil of bergamot or scented shampoo (Clairol Daily Defense) and turned on. The diffuser will remain on for the duration of the infusion, and will stay on for one hour following the infusion. Recorded measures of emesis, other adverse events, and any use of antiemetics or sedatives will be collected from patients' charts. The amount of DMSO used in each patient's graft will also be recorded in order to assess the contribution of DMSO levels to these symptoms.

Contact Information:

Elena Ladas, RD, MS
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

back to top

Antioxidant Deficiency in Children with Newly Diagnosed Acute Lymphoblastic Leukemia (ALL)

Status: Data analysis; study closed to recruitment.

Background
Little is known about the effects of antioxidant supplementation during chemotherapy treatment for cancer. There is some data in the adult oncology population but there is little to no data in the pediatric population. A recent report has demonstrated that a significant number of children with Acute Lymphoblastic Leukemia (ALL) are consuming vitamins and other antioxidants.
The anthracyclines, which are part of the standard treatment of ALL, are postulated to exert their cytotoxicity through the production of free radicals. It is therefore possible that antioxidant supplementation may reduce the efficacy of these agents. Alternatively, antioxidant supplementation could aid the repair process of normal tissues damaged by anthracycline mediated free radical production thus allowing patients to tolerate the chemotherapy better and therefore enhance the efficacy of the treatment protocol.

Purpose
To determine plasma and bone marrow antioxidants levels (beta-carotene,vitamin E, and vitamin C) and degree of oxidative stress in children before and during chemotherapy treatment for ALL and to determine if there is any correlation between antioxidant levels, oxidation status and treatment outcomes.

Patients and Methods
This observation study will look at the antioxidant/oxidation status in newly diagnosed children with ALL in order to describe what is occurring normally during chemotherapy treatment. A comprehensive picture of the antioxidant/oxidation status will be determined in 100 children with ALL by measuring the following: 1. Antioxidants- vitamin C, beta carotene and alpha tocopherol; 2. The Oxygen Radical Absorbance Capacity, a measure of total antioxidant capacity; 3. The level of 8-Hydroxydeoxyguanosine, a product of direct oxidation; 4. Dietary intake of antioxidants and macronutrients through three-day diet records and food frequency questionnaires and 5. Measures of clinical toxicity.

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Fort Washington Avenue, AP-7
New York, NY 10032
ejd14@columbia.edu

Refer to our Manuscripts for more information.

back to top

A Pilot Study of the Relationship of Polymorphisms in Phase I and II Detoxification Enzymes with Antioxidant Status in Children Undergoing Therapy for Acute Lymphoblastic Leukemia (ALL)

Status: Data analysis; study closed to recruitment

Purpose

Many patients with cancer have been taking some form of complementary therapy in the hopes of protecting their healthy cells, enhancing the effects of chemotherapy and/or protecting themselves from the late-effects of anticancer therapy. Late-effects are of particular concern in the pediatric population. Recent surveys have found 85% of pediatric patients on standard Children's Cancer Group protocols are taking some form of complementary/alternative medicine. Of recent interest has been the safety of antioxidant supplementation. There is little data regarding the safety and efficacy of antioxidant supplementation in adults with cancer. There is no data in children.

Detoxification enzymes play a role not only in cell protection, but have been shown to play a critical role in metabolism of drugs used in chemotherapy. Studies have shown that children lacking activity of key detoxification enzymes have a higher rate of toxicity from chemotherapy, adverse prognosis, and are at higher risk for therapy-related cancers.

The present study is proposing to expand a multi-institutional study (ALL/Antioxidant Study) determining the effect of chemotherapy on antioxidant status in children with acute lymphoblastic leukemia (ALL). In the ALL/Antioxidant study, DNA damage and antioxidant status was observed at diagnosis and as patients progress through therapy. Preliminary findings have shown that antioxidant status (a measure of a cell's capacity to quench damaging molecules) is adversely affected by anticancer therapy. The current proposal will expand the data by analyzing the DNA for variations in detoxification enzymes. Individual differences in detoxification enzymes will be determined from DNA saved from subjects at diagnosis. In order to determine the severity that chemotherapy affects the antioxidant capacity of children with cancer, a secondary aim of this proposal will be to determine reference values in healthy children. Siblings of children with ALL will be asked to donate 14cc of blood to determine antioxidant status and levels of DNA damage.

Patients and Methods

We are proposing to develop reference values in 45 healthy children for antioxidant status and levels of DNA damage. Parents of the children recruited for the ALL/Antioxidant study will be approached in clinic or over the phone by their physician or nutritionist and asked if their child has a healthy sibling who could donate blood to develop reference values. We have chosen this study population so we observe the influence of genes after controlling for environment. Since antioxidant status is affected by dietary intake, parents of siblings will be asked to complete a dietary recall of their child's diet in the past 24 hours and a food frequency questionnaire, which depicts their child's diet over the last three months.

Study Procedures

The Core Facility at the Herbert Irving Cancer Center of Columbia University in New York, under the direction of Dr. Regina Santella, will process and allocate the serum specimens. DNA analysis for detoxification enzymes and DNA damage will be completed at Dr. Regina Santella's laboratory. Analysis of serum micronutrients and oxygen radical absorbence capacity (ORAC) will be completed at the at the Phytochemistry laboratory, USDA, Human Nutrition Research Center on Aging at Tufts University. Dietary analysis will be completed by our nutritionist.

Contact Information:

Elena Ladas, RD, MS
Division of Pediatric Oncology
Columbia University
161 Fort Washington Avenue, AP-7
New York, NY 10032
ejd14@columbia.edu

Refer to our Manuscripts for more information.

back to top

A Retrospective Review to Assess the Feasibility of a Complementary/Alternative Medicine (CAM) Intervention Program in Survivors of Childhood Cancer

Status: Study completed

Study Purpose and Rationale

In 1998, the Division of Pediatric Oncology, Columbia University pioneered the first Complementary and Alternative Medicine (CAM) program in pediatric oncology. Most recently, in 2004, we initiated a CAM intervention program in survivors of childhood cancer. The intervention program has applied the successful model of ITPCC for children actively receiving cancer therapy to our off therapy patients. Practitioners who are experienced in the pediatric oncology population provide physical fitness classes, nutrition education and counseling sessions, and reduction of stress through the use of deep breathing and meditative techniques so as to help support behavioral change. The purpose of this study is to review preliminary information from the CAM intervention program (including heights, weight changes, heart rate changes, endurance and strength training test results), collected between July 2004 through June 2005, and to use the information to develop future grant proposals.

Study Design and Statistical Procedures

This study is a retrospective review. The analysis will be descriptive in nature. The study population is the 10 patients who have enrolled in the program. Trends in preliminary information over the past year will be analyzed. Pre and post changes in the following outcomes: dietary patterns, heights, weight changes, heart rate changes, endurance and strength training test results will be analyzed. If changes are observed, further investigation may be warranted in follow up studies.

Study Procedures

The proposed retrospective review will enable us to determine if the program has been successful. The data analyzed will allow the investigators to analyze the success of our survivorship program and identify improvements that must be made to the program so as to further benefit the patients. Participant information, such as height, weight, heart rate,waist size, and dietary patterns has been recorded since the initiation of the program and will be analyzed. The information collected will provide preliminary data for inclusion into future grant reports and case series reports.

Contact Information:

Elena Ladas, RD, MS
Division of Pediatric Oncology
Columbia University
161 Fort Washington Avenue, AP-7
New York, NY 10032
ejd14@columbia.edu

back to top

Use of Unconventional Therapies by Children With Cancer at an Urban Medical Center

Status: Study completed

Purpose

The aim of this study was to determine the prevalence, modalities, and determinants of use of unconventional therapies among children with cancer receiving conventional treatment at an urban academic medical center in the United States.

Patients and Methods

We interviewed the parents of patients and/or patients who were receiving or had received conventional therapy for treatment of childhood cancer. Of 78 patients/parents asked, 75 consented to the interview, which included demographic factors, life events, and use of unconventional therapies. All participants also consented to the abstraction of chart data for this study.

Results

Overall, 84% of respondents reported the use of one or more unconventional therapies. The most commonly used modalities were changes in diet, nutritional and herbal agents, and mind/body treatments. Most users had tried more than one unconventional modality. No difference in use was seen by cancer diagnosis, race/ethnicity, socio-economic status, or educational attainment of the respondent. Of the therapies used, 50% were not reported to the physicians. Of patients reporting use of an unconventional approach, 85% were concurrently enrolled on clinical trials for primary treatment of their cancer.

Conclusions

The use of unconventional therapies is highly prevalent among children with cancer and it is not associated with demographic or clinical factors or participation in clinical trials. The possibility that an unconventional treatment may interact with a protocol treatment underscores the need for more information about the use of such therapies among all patients.

Contact Information:

Kara M Kelly, MD
Division of Pediatric Oncology
Columbia University
161 Fort Washington Avenue, AP-7
New York, NY 10032
kk291@columbia.edu

Refer to our Manuscripts for more information.

back to top

A Retrospective Review to Assess the Nutritional Status and Physical Fitness Level of Pediatric Oncology Survivors in the Survivor Wellness Program

Status: Data Analysis

Study Purpose and Rationale

Even after the completion of cancer treatment, approximately two-thirds of survivors of childhood cancers experience late-effects associated with the anticancer therapy. The National Cancer Policy Board states that the patterns of late effects emerging in groups of childhood cancer survivors has led to the appreciation of cancer as a chronic disease with implications for continuing care. The Center for Survivor Wellness in the Division of Pediatric Oncology at Columbia University is aimed at helping survivors of childhood cancer make healthy lifestyle choices in order to decrease the likelihood and severity of late effects. Recent recommendations for survivors of childhood cancer intervention programs aimed at modifying lifestyle behaviors include patient education on increasing the frequency and duration of physical activity, improved dietary choices, and providing methods for managing stress.

Because of the paucity of information examining the relationship between lifestyle behaviors and the incidence of late effects for survivors of childhood cancers, the proposed retrospective review will examine the baseline dietary habits and physical fitness levels for survivors enrolled in the Center for Survivor Wellness in the Division of Pediatric Oncology at Columbia University. The information collected will aid in providing information to the survivor population as well as direct future research priorities.

Study design and Statistical Section

This study is a retrospective review. The analysis will be descriptive in nature. The study population involves approximately 50 patients who have participated in the Survivor Wellness Program.

Study Procedures

The retrospective review will assess the baseline dietary choices and physical fitness levels of survivors of childhood cancers. Information about the participants’ dietary choices includes the number of fruit and vegetable servings, the total caloric intake, and labs such as HGB and cholesterol panels. The data used to measure physical fitness level is the peak oxygen consumption, peak heart rate, and maximum amount of weight lifted. We will also collect demographic information including age at diagnosis of cancer, current age, gender, and body mass index. We will also collect information on cancer diagnosis, type of cancer treatment (chemotherapy, radiation therapy and surgery) as well as any other comorbid conditions. No identifying information will be collected.

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

back to top

A Retrospective Review to Assess the Feasibility of an Acupuncture Program in Pediatric Oncology

Status: Data analysis

Study Purpose and Rationale

In 1998, the Division of Pediatric Oncology, Columbia University pioneered the first Complementary and Alternative Medicine (CAM) program in pediatric oncology. In March, 2005, we expanded the scope of services offered to patients to include acupuncture. Licensed acupuncturists, experienced in the pediatric oncology population, provide supportive care and symptom management services to patients and their families. The purpose of this study is to review preliminary information from the acupuncture program (including patient and family response, chief symptom complaint, overall experience, change in symptoms, and Chinese medicine diagnosis and treatment plan), collected since the initiation of the service.

Study Design and Statistical Procedures

This study is a retrospective review. The analysis will be descriptive in nature. The study population is the patients, families, and staff who have participated in the program. Participants' experience with acupuncture over the past year will be analyzed.

Study Procedures

The proposed retrospective review will enable us to determine if providing acupuncture to children with cancer and their families is feasible. The data analyzed will guide future grant submissions and allow the investigators to assess the success of the acupuncture program and to identify areas of improvements. Information, such as response, chief symptom complaint, overall experience, change in symptoms, and Chinese medicine diagnosis and treatment plan, has been recorded since the initiation of the program and will be analyzed. The information collected will provide preliminary data for inclusion into future grant proposals, case series reports, and health service and programming reports.

Contact Information:

Elena Ladas, MS, RD
Division of Pediatric Oncology
Columbia University
161 Ft. Washington Ave, IP-7
New York, NY 10032
ejd14@columbia.edu

Refer to our Manuscripts for more information.

back to top

For Information on Clinical trials in Pediatric Cancer and Alternative Complementary Medicine...

Contact the Office of Cancer Complementary and Alternative Medicine at NIH (http://www.cancer.gov/cam/).

OR

Contact The Children's Oncology Group Complementary Therapies Committee. The Children's Oncology Group (COG) was formed by the merger of four national pediatric cancer research organizations: the Children's cancer Group, the Intergroup Rhabdomyosarcoma Study Group, the National Wilm's Tumor Study Group and the Pediatric Oncology Group. The primary objective is to conduct clinical trials of new therapies for childhood cancer. At present, these groups are achieving a cure rate of approximately 70% for children with cancer. Nearly 90% of the children with cancer in North America have access to the state-of-the-art care of the physician-researchers who belong to COG. Members are located at over 235 prestigious medical centers.

The Cancer Control committee of COG has initiated a subcommittee to specifically develop research studies on complementary alternative medicine (CAM) for children with cancer. The subcommittee is chaired by Kara Kelly, MD and Susan Sencer, MD. The goals of the Complementary Therapies committee are:

1. To develop evidence based research in complementary therapies and pediatric cancer in areas of efficacy, impact on therapy and quality of life.
2. To educate pediatric oncology caregivers about complementary therapies as it relates to pediatric oncology.

OR

Contact the PDQ National Cancer Institute at NIH (http://www.cancer.gov/cancerinfo/), comprehensive database of ongoing clinical trials in cancer. Summaries of completed research on specific CAM agents can be found at (http://www.cancer.gov/cancerinfo/pdq/treatment/). You can contact the office directly by calling 1-800-4-CANCER or by accessing the website.

Last updated: November 20, 2009