Predicting Response to Standardized Pediatric Colitis Therapy
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Study type: Interventional
Phase: Phase 4

Summary: 
      This is a multi-center, open-label study to determine the safety and effectiveness (how well
      it works) of two standardized treatments called "mesalamine" (Pentasa®) and "prednisone" in
      children with newly diagnosed Ulcerative Colitis (UC). Standardized treatments are types of
      treatments agreed upon and used by many qualified doctors. The medications being used in this
      study are considered "standard of care". Currently the ways in which these medicines are used
      (doses, frequency of dosing) may vary from site to site. This study will determine response
      to a standardized way of giving these medicines.

      This study will also identify biomarkers for ulcerative colitis. Biomarkers are things that
      doctors can find in blood, stool, or bowel tissue that indicate how much inflammation there
      is in the bowel, how the inflammation is produced, and whether the inflammation is responding
      to treatment. Collecting response and remission (free of symptoms) information on these
      standardized treatments and the "biomarkers" can possibly help doctors create a model, or
      plan to know which children with UC may respond quickly, or which children may develop
      complications.
    

Detailed description: 
      Ulcerative Colitis (UC) denotes a phenotype of chronic inflammatory bowel disease (IBD),
      where inflammation is localized to the colonic mucosa, and extends from the rectum proximally
      in varying extents. The disorder is thought to result from an inappropriate activation of the
      mucosal immune system by antigens derived from both the host epithelium and the enteric
      flora, in genetically susceptible individuals. UC is strikingly heterogeneous with respect to
      age of onset, anatomical extent and disease course, with some experiencing chronically active
      severe disease, while others have intermittent periods of clinical remission and disease
      exacerbation. Patients' therapeutic responses vary. The reasons underlying such variability
      are not well understood. Although it has been widely hypothesized that several genes may
      influence the development of UC, and modify its phenotypic expression and severity, to date
      there are few confirmed examples of such relationships.

      It has been postulated that the 5-aminosalicylate drugs exert their anti-inflammatory effect
      locally at the intestinal mucosa. Mechanisms likely include inhibition of 5-lipoxygenase
      resulting in decreased production of leukotriene B4, scavenging of reactive oxygen
      metabolites, prevention of up-regulation of leukocyte adhesion molecules, and inhibition of
      Interleukin 1 (IL-1) synthesis. Though multiple studies have shown the efficacy of
      aminosalicylates in inducing and maintaining remission in adults with UC, there are few data
      in children.

      Corticosteroids (CS) have been the mainstay of treatment of severe UC since efficacy was
      first demonstrated in the 1955 randomized controlled trial by Truelove and Witts. Recent
      practice guidelines developed in adults support their use because of rapid onset of action
      and significant efficacy though CS dependency is noted. Though no controlled data on their
      use have been reported in children they are frequently used in this population. A recent
      report from investigators leading the prospective Pediatric IBD Collaborative Research Group
      Registry described 97 subjects with a diagnosis of UC and a minimum of 1 year follow-up; 79%
      received CS. At diagnosis 81% of CS treated patients had moderate/severe disease, and 81% had
      pancolitis. Clinically inactive disease, determined by physician global assessment, was noted
      in 60% at 3 months following CS therapy, but by one year 45% were considered CS dependent
      despite the frequent use of immunomodulators (IM). Among those children with initially
      moderate to severe disease in clinical remission at 3 months, about two-thirds had stopped
      the CS by one year.
    

Intervention name(s): Mesalazine; IV Corticosteroid; Oral Corticosteroids; Additional Therapies; Colectomy
Intervention type(s): Drug; Drug; Drug; Other; Procedure
Intervention description(s): Mesalazine (Pentasa) comes in 500mg capsules, and doses will need to be rounded to the nearest 500mg increment, with a maximum dose of 76 mg/kg/day. The average dose for the pediatric population will be approximately 70 mg/kg/day. Patients will be allowed to escalate to the final dose over 4 days to minimize side-effects such as headache.; Treatment with IV Corticosteroid; Treatment with oral corticosteroids; Anti-TNFα, Calcineurin inhibitor, Immunomodulator; Colectomy
Other intervention name(s): Pentasa; Prednisone; Prednisone
Intervention MeSH terms: Prednisone; Mesalamine
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Ulcerative Colitis; mesalamine; corticosteroids; PROTECT