A Phase II Randomized Trial of Growth Hormone Therapy in Pediatric Crohn's Disease
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 22
- Locations
- 1
- Primary Endpoint
- Crohn's Disease Histologic Index of Severity (CDHIS)
Study Overview
Brief Summary
The purpose of this study is to determine whether taking a growth hormone (GH) drug called somatropin causes the intestine of a person with Crohn's Disease (CD) to heal faster when compared to a person with Crohn's Disease that does not receive growth hormone drug.
Detailed Description
The optimal treatment goals in childhood CD include: 1) clinical remission in conjunction with mucosal healing and 2) restoration of normal growth and development. Current therapy in most cases includes induction of remission with corticosteroids followed by maintenance of remission with 6-mercaptopurine (6-MP) or mesalamine. With this approach, the goals of achieving mucosal healing with normalization of growth are not achieved in a significant number of children. GH therapy is now used in several chronic childhood diseases which are complicated by growth failure despite adequate GH secretion. These include chronic renal failure (CRF), juvenile rheumatoid arthritis (JRA), and Turner's syndrome. However, despite a comparable frequency and magnitude of permanent growth failure, the efficacy of GH therapy in this respect has not yet been determined in a controlled trial for CD. Moreover, whether GH therapy may also directly reduce disease activity and promote intestinal healing is not known. This represents a significant clinically unmet need in this patient population. Therefore, new therapeutic approaches are needed to both improve final adult height and enhance intestinal mucosal healing in children with CD.
The primary objective of this study is to determine the effect of growth hormone (GH) therapy upon colon mucosal healing in a 12 week randomized trial in children with Crohn's Disease (CD). Children with active CD will be randomized to GH + prednisone (GP) or prednisone alone (P) for a 12 week period. This study also involves a 52 week extension phase where all participants that meet eligibility will be given the opportunity to take or continue taking growth hormone for 52 weeks.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 5 Years to — (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Ability to provide written informed consent
- •Age ≥ 5 years.
- •Diagnosis of Crohn's disease (CD) with ileo-colonic involvement as determined by standard clinical, radiological, and pathological criteria.
- •Moderate to severely active CD as defined by a PCDAI (Pediatric Crohn's Disease Activity Index) ≥
- •Currently taking Prednisone or Budesonide at starting dose (not tapering)
- •May continue stable doses of AZA/6-MP, methotrexate, and/or mesalamine at entry.
- •For the 52 week extension, baseline bone age ≤ 12 years for girls and ≤ 13 years for boys.
- •For the 52 week extension phase, remission or mild Crohn's disease as determined by a PCDAI < 30.
Exclusion Criteria
- •Acute critical illness
- •Active neoplasia
- •Diabetes mellitus
- •History of intracranial lesion and/or neoplasia
- •Severe disease requiring hospitalization for treatment
- •Current therapy with infliximab as this may independently rapidly reduce clinical disease activity and promote mucosal healing
- •Use of prednisone or budesonide and in tapering phase
- •Family history of colorectal cancer before age 50
- •Personal or familial history of familial polyposis syndrome
- •Pregnancy (positive pregnancy test) prior to randomization
- •Any other condition that the investigator believes would pose a significant hazard to the subject if the investigational therapy were initiated
- •Participation in another simultaneous medical investigation or trial other than the Pediatric IBD (Inflammatory Bowel Disease) registry
Arms & Interventions
Growth Hormone plus cortecosteroid
Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Intervention: growth hormone (Drug)
Cortecosteroids alone
Cortecosteroid therapy as prescribed by the referring gastroenterologist
Intervention: cortecosteroid (Drug)
Outcomes
Primary Outcomes
Crohn's Disease Histologic Index of Severity (CDHIS)
Time Frame: Baseline and 12 weeks
The CDHIS was developed and validated in order to determine the effect of therapies upon histologic disease activity in Crohn's Disease. It has been used to assess mucosal healing in response to infliximab and 6-MP/AZA.It contains eight items which reflect epithelial injury, mucosal inflammation, and the extent of involvement. Scores range from 0-16, with patients with moderate to severely active CD typically having scores of 6-12. It was computed by a GI pathologist. The higher the score indicates worsening of disease, the lowest score is 0 and highest possible is 16
Secondary Outcomes
- Serum IGF-1 (Insulin-like Growth Factor 1)z Score(Baseline, 12 weeks, 24 weeks)
- IMPACT III Score(Baseline, 12 weeks, 24 weeks)
- Pediatric Crohn's Disease Activity Index (PCDAI)(Baseline, 12 and 24 weeks)
- Total Corticosteroid Use(12 weeks)
- Crohn's Disease Endoscopic Index of Severity (CDEIS)(Baseline and 12 weeks)
- Height Velocity(Baseline, week 12, 24 and 48)
- Fecal Calprotectin(At 24 and 64 weeks)