Trial of Growth Hormone Therapy in Pediatric Crohn's Disease
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase II Randomized Trial of Growth Hormone Therapy in Pediatric Crohn's Disease|
- Crohn's Disease Histologic Index of Severity (CDHIS) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]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
- Serum IGF-1 (Insulin-like Growth Factor 1)z Score [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: Yes ]
Elevated serum IGF-1 levels have been implicated in the development of colorectal cancer, both in the general population and in patients with an excess of growth hormone production. The serum IGF-1 levels were monitored to maintain them in the physiologic range during growth hormone therapy to reduce the risk of tumorigenesis.
The levels are reported as a z score, a statistical way of standardizing data. The standard deviation is the unit of measurement of the z-score. Each z score corresponds to a point in a normal distribution, describing how much a point deviates from a mean.
- IMPACT III Score [ Time Frame: Baseline, 12 weeks, 24 weeks ] [ Designated as safety issue: No ]Health-related quality of life (QOL)was assessed using the IMPACT 111 questionnnaire. It is a self-administered 35 item questionnaire which typically takes 10-15 minutes to complete. Scores range from 0-350, with higher scores reflecting better perceived quality of life.
- Pediatric Crohn's Disease Activity Index (PCDAI) [ Time Frame: Baseline, 12 and 24 weeks ] [ Designated as safety issue: No ]The PCDAI is a previously validated measure of clinical disease activity for children with CD. It contains three self-report items which reflect patient abdominal pain, diarrhea, and general well being; three laboratory values; height and weight velocity; and three physical examination parameters reflecting abdominal tenderness, perirectal disease, and extra-intestinal manifestations. Scores may range from 0-100. Remission is defined as 0-10, mild disease as 10-30, and moderate to severe disease as greater than 30.
- Total Corticosteroid Use [ Time Frame: 12 weeks, 24 weeks ] [ Designated as safety issue: No ]
- Crohn's Disease Endoscopic Index of Severity (CDEIS) [ Time Frame: Baseline and 12 weeks ] [ Designated as safety issue: No ]Measure of mucosal disease at baseline and week 12 obtained during colonoscopy. The CDEIS score generally ranges from 0-30. A higher score indicates more severe mucosal inflammation.
- Height Velocity [ Time Frame: Baseline, week 12, 24 and 48 ] [ Designated as safety issue: No ]
Height velocity was computed every 12 weeks up to week 64 and then yearly during the Maintenance study. Since 40 to 80% of children with Crohn's disease have significant growth failure at diagnosis, height velocity is used to track for changes in height.
It is calculated by measuring height at two points of time and then dividing the change by the amount of time.
- Fecal Calprotectin [ Time Frame: At 24 and 64 weeks ] [ Designated as safety issue: No ]Fecal calprotectin is a previously validated stool marker of intestinal inflammation in Crohn's Disease.
|Study Start Date:||April 2005|
|Study Completion Date:||August 2009|
|Primary Completion Date:||July 2009 (Final data collection date for primary outcome measure)|
Experimental: Growth Hormone plus cortecosteroid
Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
Drug: growth hormone
Nutropin AQ 0.075mg/kg/day subcutaneously daily
Other Name: Nutropin AQ
Active Comparator: Cortecosteroids alone
Cortecosteroid therapy as prescribed by the referring gastroenterologist
As prescribed by the referring gastroenterologist
Other Name: Prednisone, Entocort
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00109473
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|Principal Investigator:||Lee Denson, M.D.||Children's Hospital Medical Center, Cincinnati|