Back to resultsGrowth Hormone and Exclusion Diet Therapy in Juvenile Crohn's Disease
Primary Purpose
Crohn's Disease
Status
Withdrawn
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Growth Hormone
Nutraceutical Combination
Exclusion Diet
Placebo Growth Hormone
Sponsored by
About this trial
This is an interventional treatment trial for Crohn's Disease focused on measuring Crohn's disease, Inflammatory Bowel Disease, Growth Hormone, Nutraceuticals
Eligibility Criteria
Inclusion Criteria:
- Ability to provide written informed consent
- Age 10-17 years
- Diagnosis of CD as determined by standard clinical, radiological, and pathological criteria
- Clinical evidence of CD for more than 2 years
- Moderate to severely active CD, as defined by a PCDAI score > 30 and < 65
- May continue use of aminosalicylates, antibiotics, immunomodulators, including azathioprine, 6-mercaptopurine and methotrexate, as well as the monoclonal antibody drug, infliximab, if prescribed for at least 4 months and receiving stable doses for at least 2 months prior to baseline visit
- May continue the use of prednisone if prescribed for at least 6 weeks prior to baseline visit
Meets the following hematological and biochemical requirements:
- HGB > 8.5 g/dl
- WBC > 3.5 x 109/L
- Neut. > 1.5 x 109
- Plats > 100 x 109/L
- SGOT & Alk Phos not > 2 times the upper limit of normal
Exclusion Criteria:
- Acute critical illness
- Acute, chronic, or latent infection
- Active neoplasia and/or history of neoplastic disease of any origin other than basal cell carcinoma that has been removed
- Evidence of a systemic disorder unrelated to CD involving hepatic, gastrointestinal, pulmonary, cardiac, renal, hematologic, endocrine, central or peripheral nervous systems
- Use of parenteral corticosteroids or corticotrophin within 2 months of baseline visit
- Use of another investigational agent within 3 months of baseline visit
- Long-term anti-coagulant therapy or use of any anti-coagulant medication, including NSAIDs or ASA, within 2 weeks of screening visit
- Pregnancy (positive pregnancy test)
- Positive stool culture for enteric pathogens, pathogenic ova, parasites or clostridium difficile toxin
- Any condition that the investigator believes would pose significant harm to the subject if the investigational therapy were initiated
- Diagnosis of short bowel syndrome and also on TPN
- Presence of an ostomy, symptomatic stenosis or ileal stricture, or severe intestinal stricture, proctocolectomy, total colectomy or stoma
- Patients in imminent need of surgery due to active gastrointestinal bleeding fixed stenosis, intermittent obstruction or obstructive event within 2 months prior to screening.
- Patients who underwent CD surgery within 2 months of screening
Sites / Locations
- Columbia University Department of Clinical Genetics
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
Growth Hormone, Exclusion Diet, and Nutraceutical therapy
rhGH placebo, Exclusion diet, and nutraceutical therapy
Arm Description
The experimental group will receive the exclusion diet and nutraceutical therapy (DNT) and daily subcutaneously administered recombinant human growth hormone (rhGH) for the first 26 weeks. After 26 weeks this group will continue on the exclusion diet nutraceutical therapy for the remaining 26 weeks of the study.
The experimental group will receive the exclusion diet and nutraceutical therapy (DNT) and daily subcutaneously administered placebo injections for the first 26 weeks. After 26 weeks this group will continue on the exclusion diet and nutraceutical therapy for the remaining 26 weeks of the study.
Outcomes
Primary Outcome Measures
Proportion of Patients in remission
The proportion of patients in remission in each group will be assessed and compared to each other in order to demonstrate efficacy of treatment. Remission will be assessed by a change in the patients PCDAI score to below 10.
Secondary Outcome Measures
Bone Mineral Density (BMD)
BMD of the hip and spine will be obtained by dual-emission x-ray absorptiometry (DXA) at the baseline visit and week 52.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT01647412
Brief Title
Growth Hormone and Exclusion Diet Therapy in Juvenile Crohn's Disease
Official Title
Growth Hormone and Nutrition Therapy in Juvenile Crohn's Disease, a Randomized Clinical Trial
Study Type
Interventional
2. Study Status
Record Verification Date
April 2015
Overall Recruitment Status
Withdrawn
Why Stopped
PI left the institution
Study Start Date
March 2012 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
undefined (undefined)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Columbia University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Of the estimated one million Americans with inflammatory bowel disease (IBD), approximately 20-30% develop this condition during childhood or adolescence, most of whom have Crohn's disease (CD). It appears that some individuals are genetically susceptible to certain nutrients, causing inflammation and disturbance of their immune system, as well as disruption of the intestinal barrier. This leads to malnutrition and inhibited growth, with many patients experiencing intense abdominal pain and diarrhea.
Most physicians treat the disease with drugs that suppress the immune system and decrease the inflammatory process. Although these drugs frequently induce remission, most patients experience a subsequent return of symptoms and fail to catch up on their growth. Additionally, serious side effects are associated with these drugs.
Individuals genetically prone to CD are believed to have a leaky gut that allows substances to pass through the intestinal wall and react with the underlying immune system. Furthermore, those nutrients that are toxic to these individuals pass through the decreased intestinal barrier triggering an extreme immune response. Nutrients that have been implicated include grains, except rice, dairy products, and any food containing carrageenan. Excluding these nutrients from the diet has been shown to beneficial for CD patients. Certain nutraceuticals, such as curcumin and omega-3 fatty acids, have been shown to provide anti-inflammatory effects in IBD patients. In addition, the administration growth hormone (GH), has been shown to alleviate symptoms, by enhancing the repair of the intestinal epithelium, preventing toxic antigens from reaching the underlying lamina propria.
Previous studies and case reports provide incomplete evidence that exclusion diet with nutraceuticals (DNT) and GH lead to sustained long term remission in juvenile CD, discontinuation of other CD drugs, and catch up growth. This study is designed to test this hypothesis. Patients in the treatment group will be treated with DNT and GH, while continuing to receive medications from their physician while the control group will receive DNT, placebo injections instead of GH. We predict that the treatment group will show greater improvement than the control group.
Detailed Description
The most widely held hypothesis regarding the pathogenesis of inflammatory bowel disease (IBD) is that overly aggressive acquired immune responses to a subset of commensal enteric bacteria develop in genetically susceptible hosts. In an attempt to avoid disease progression, patients are treated with anti-inflammatory, immunomodulatory and monoclonal antibody drugs, which frequently produce remissions. However, these drugs usually fail to achieve long-term, sustained remission or reversal of growth failure, and are associated with serious side effects. Recently, intestinal barrier dysfunction has been implicated in an alternative 3-step model of IBD pathogenesis.
The investigators hypothesize that the exclusion diet and nutraceutical therapy (DNT) will decrease the production of toxic antigens in the gut and that reactive human growth hormone (rhGH) will reduce the passage of the remaining toxic antigens to the underlying mucosal immune system by promoting the maintenance of the intestinal barrier and accelerating the restitution of the intestinal epithelial lining.
The following study will test whether the the 3-step model is accurate, and whether rhGH and DNT will induce sustained remission in juvenile CD patients.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
Keywords
Crohn's disease, Inflammatory Bowel Disease, Growth Hormone, Nutraceuticals
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Growth Hormone, Exclusion Diet, and Nutraceutical therapy
Arm Type
Active Comparator
Arm Description
The experimental group will receive the exclusion diet and nutraceutical therapy (DNT) and daily subcutaneously administered recombinant human growth hormone (rhGH) for the first 26 weeks. After 26 weeks this group will continue on the exclusion diet nutraceutical therapy for the remaining 26 weeks of the study.
Arm Title
rhGH placebo, Exclusion diet, and nutraceutical therapy
Arm Type
Placebo Comparator
Arm Description
The experimental group will receive the exclusion diet and nutraceutical therapy (DNT) and daily subcutaneously administered placebo injections for the first 26 weeks. After 26 weeks this group will continue on the exclusion diet and nutraceutical therapy for the remaining 26 weeks of the study.
Intervention Type
Drug
Intervention Name(s)
Growth Hormone
Intervention Description
Humatrope will be administered daily to patients in a dose of .18-.20 mg/kg/week.
Intervention Type
Dietary Supplement
Intervention Name(s)
Nutraceutical Combination
Other Intervention Name(s)
Jarrow Curcumin oral capsule bid, Jarrow Max DHA (Fish oil) oral capsule daily, Culturelle Probiotics oral capsule tw, Intestive oral capsule bid, Nutrient 950 without Iron (Multivitamin) oral capsule daily
Intervention Type
Other
Intervention Name(s)
Exclusion Diet
Intervention Description
Patients on the exclusion diet will adhere from consumption of all grain, corn, dairy, and carrageenan containing products.
Intervention Type
Other
Intervention Name(s)
Placebo Growth Hormone
Primary Outcome Measure Information:
Title
Proportion of Patients in remission
Description
The proportion of patients in remission in each group will be assessed and compared to each other in order to demonstrate efficacy of treatment. Remission will be assessed by a change in the patients PCDAI score to below 10.
Time Frame
26 weeks and 52 weeks
Secondary Outcome Measure Information:
Title
Bone Mineral Density (BMD)
Description
BMD of the hip and spine will be obtained by dual-emission x-ray absorptiometry (DXA) at the baseline visit and week 52.
Time Frame
Baseline and 52 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
10 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ability to provide written informed consent
Age 10-17 years
Diagnosis of CD as determined by standard clinical, radiological, and pathological criteria
Clinical evidence of CD for more than 2 years
Moderate to severely active CD, as defined by a PCDAI score > 30 and < 65
May continue use of aminosalicylates, antibiotics, immunomodulators, including azathioprine, 6-mercaptopurine and methotrexate, as well as the monoclonal antibody drug, infliximab, if prescribed for at least 4 months and receiving stable doses for at least 2 months prior to baseline visit
May continue the use of prednisone if prescribed for at least 6 weeks prior to baseline visit
Meets the following hematological and biochemical requirements:
HGB > 8.5 g/dl
WBC > 3.5 x 109/L
Neut. > 1.5 x 109
Plats > 100 x 109/L
SGOT & Alk Phos not > 2 times the upper limit of normal
Exclusion Criteria:
Acute critical illness
Acute, chronic, or latent infection
Active neoplasia and/or history of neoplastic disease of any origin other than basal cell carcinoma that has been removed
Evidence of a systemic disorder unrelated to CD involving hepatic, gastrointestinal, pulmonary, cardiac, renal, hematologic, endocrine, central or peripheral nervous systems
Use of parenteral corticosteroids or corticotrophin within 2 months of baseline visit
Use of another investigational agent within 3 months of baseline visit
Long-term anti-coagulant therapy or use of any anti-coagulant medication, including NSAIDs or ASA, within 2 weeks of screening visit
Pregnancy (positive pregnancy test)
Positive stool culture for enteric pathogens, pathogenic ova, parasites or clostridium difficile toxin
Any condition that the investigator believes would pose significant harm to the subject if the investigational therapy were initiated
Diagnosis of short bowel syndrome and also on TPN
Presence of an ostomy, symptomatic stenosis or ileal stricture, or severe intestinal stricture, proctocolectomy, total colectomy or stoma
Patients in imminent need of surgery due to active gastrointestinal bleeding fixed stenosis, intermittent obstruction or obstructive event within 2 months prior to screening.
Patients who underwent CD surgery within 2 months of screening
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alfred E Slonim, MD
Organizational Affiliation
Columbia University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Columbia University Department of Clinical Genetics
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
12. IPD Sharing Statement
Learn more about this trial
Growth Hormone and Exclusion Diet Therapy in Juvenile Crohn's Disease
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