Trial of Growth Hormone Therapy in Pediatric Crohn's Disease

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.

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