Trial of Growth Hormone Therapy in Pediatric Crohn's Disease

• ClinicalTrials.gov Identifier: NCT00109473
• Recruitment Status: Completed
• First Posted: April 29, 2005
• Results First Posted: September 16, 2011
• Last Update Posted: October 30, 2020
• Sponsor: Children's Hospital Medical Center, Cincinnati
• Collaborator: Genentech, Inc.
• Information provided by (Responsible Party): Children's Hospital Medical Center, Cincinnati

Tracking Information

• First Submitted Date: April 28, 2005
• First Posted Date: April 29, 2005
• Results First Submitted Date: June 24, 2011
• Results First Posted Date: September 16, 2011
• Last Update Posted Date: October 30, 2020
• Study Start Date: April 2005
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 10, 2011)

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

• Original Primary Outcome Measures (submitted: June 23, 2005): Crohn's Disease Histologic Index of Severity

Current Secondary Outcome Measures (submitted: October 27, 2020)

• 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 ]
  The total corticosteroid use over 12 weeks between groups, using the unpaired t test.
• 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 Measures (submitted: June 23, 2005)

• 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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Trial of Growth Hormone Therapy in Pediatric Crohn's Disease
• 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 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 Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Crohn's Disease

Intervention

• Drug: growth hormone
  Nutropin AQ 0.075mg/kg/day subcutaneously daily
  Other Name: Nutropin AQ
• Drug: cortecosteroid
  As prescribed by the referring gastroenterologist
  Other Name: Prednisone, Entocort

Study Arms

• Experimental: Growth Hormone plus cortecosteroid
  Growth Hormone (nutropin AQ 0.075 mg/kg/day subcutaneously daily)
  Intervention: Drug: growth hormone
• Active Comparator: Cortecosteroids alone
  Cortecosteroid therapy as prescribed by the referring gastroenterologist
  Intervention: Drug: cortecosteroid

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 7, 2009): 22
• Original Enrollment (submitted: June 23, 2005): 28
• Actual Study Completion Date: August 2009
• Actual Primary Completion Date: July 2009 (Final data collection date for primary outcome measure)

Eligibility Criteria

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) ≥ 30.
• 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 5 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT00109473
• Other Study ID Numbers: CCHMC IRB #: 04-12-06; IND # 71,344 ( Other Identifier: FDA )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Children's Hospital Medical Center, Cincinnati
• Original Responsible Party: Not Provided
• Current Study Sponsor: Children's Hospital Medical Center, Cincinnati
• Original Study Sponsor: Denson, Lee, M.D.
• Collaborators: Genentech, Inc.

Investigators

• Principal Investigator: Lee Denson, M.D.; Children's Hospital Medical Center, Cincinnati

• PRS Account: Children's Hospital Medical Center, Cincinnati
• Verification Date: October 2020