Clinical Trial: Trial of Growth Hormone Therapy in Pediatric Crohn's Disease

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Randomized Trial of Growth Hormone Therapy in Pediatric Crohn's Disease

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 Summary:

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.

Current Primary Outcome: Crohn's Disease Histologic Index of Severity (CDHIS) [ Time Frame: Baseline and 12 weeks ]

Original Primary Outcome: Crohn's Disease Histologic Index of Severity

Current Secondary Outcome:

• Serum IGF-1 (Insulin-like Growth Factor 1)z Score [ Time Frame: Baseline, 12 weeks, 24 weeks ]

  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 ]
  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 ]
  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 ]
• Crohn's Disease Endoscopic Index of Severity (CDEIS) [ Time Frame: Baseline and 12 weeks ]
  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 ]

  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 ]
  Fecal calprotectin is a previously validated stool marker of intestinal inflammation in Crohn's Disease.

Original Secondary Outcome:

• Serum IGF-1
• Colon crypt epithelial cell (CEC) proliferation labeling index
• IMPACT III
• Pediatric Crohn's disease Activity Index
• Total Corticosteroid Use
• Intra-abdominal fat
• Height Velocity

Dates:
Date Received: April 28, 2005
Date Started: April 2005
Date Completion:
Last Updated: January 11, 2017
Last Verified: January 2017