Predicting Response to Standardized Pediatric Colitis Therapy
Condition: Ulcerative Colitis
MeSH terms: Colitis; Colitis, Ulcerative; Ulcer
Intervention: Mesalazine; IV Corticosteroid; Oral Corticosteroids; Additional Therapies; Colectomy
Intervention description: 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
Intervention MeSH terms: Prednisone; Mesalamine
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 431.0
Sex: All
Minimum age: 4 Years
Maximum age: 17 Years
Healthy volunteers: No
Keywords: Ulcerative Colitis; mesalamine; corticosteroids; PROTECT

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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age ≥ 4years and ≤17 years at initiation of therapy (achieved 4th birthday, not yet
             18th)

          -  Weight ≥15 kg

          -  New diagnosis of ulcerative colitis established by standard clinical, endoscopic, and
             histologic features at the PROTECT study site

          -  Colitis extending beyond the rectosigmoid (Paris classification E2, E3, or E4)[144].
             If a patient is seriously ill and the clinician does not advance the colonoscope
             beyond the sigmoid colon but the clinical condition of the patient highly suggests
             more extensive disease then that patient is eligible for study.

          -  Disease activity by PUCAI of ≥10 at diagnosis

          -  No therapy previously initiated to treat the newly diagnosed ulcerative colitis

          -  Stool culture negative for routine enteric pathogens (Salmonella, Shigella,
             Campylobacter, E. coli 0157:H7) and Clostridium difficile toxin. Recent successful
             treatment for Clostridium difficile does not exclude a patient if toxin now absent.
             However, the patient must be a minimum of 5 weeks from the time treatment was started
             at the time toxin is absent.

          -  Stool study negative for enteric parasites (ova and parasites)

          -  Parent/guardian consent and patient assent

          -  Ability to remain in follow-up for a minimum of one year from diagnosis

          -  Female patients of child bearing age must have a negative urine pregnancy test and
             practice acceptable contraception (e.g., abstinence, intramuscular or hormonal
             contraception, two barrier methods (e.g., condom, diaphragm, or spermicide),
             intrauterine device, verbal report of the partner with history of vasectomy, or be
             surgically sterile). All female patients of childbearing potential (post-menarche)
             will undergo urine pregnancy testing at screening and must not be lactating.

        Exclusion Criteria:

          -  Clinical, endoscopic, radiologic, or histologic evidence suggesting Crohn's disease
             (CD) consistent with Paris and North American Society for Pediatric Gastroenterology,
             Hepatology and Nutrition (NASPGHAN) criteria [144, 145]

          -  A previous diagnosis of inflammatory bowel disease for which treatment was given

          -  Evidence of any active enteric infection at the time of study entry

          -  Use of any oral CS for non-gastrointestinal indication within the past 4 weeks (e.g.,
             asthma). Use of inhaled CS does not exclude a patient.

          -  History of use of IM or anti-TNFα agent for other medical conditions (e.g., juvenile
             rheumatoid arthritis) within the past 6 months

          -  Use of Accutane within the past 4 weeks

          -  Use of any investigational drug within the past four weeks

          -  Use of any 5-aminosalicylate within the past 4 weeks

          -  Pregnancy

          -  Subjects with poorly controlled medical conditions (e.g. diabetes, congestive heart
             failure)

          -  Proctitis or proctosigmoiditis only (Paris classification E1) on colonoscopic
             evaluation

          -  Chronic renal disease (BUN and serum creatinine >1.5 times the upper normal limit)

          -  Hepatic disease (AST or Alkaline phosphatase (ALP) greater than 3 times the upper
             normal limit in the absence of concomitant liver disease associated with IBD following
             full evaluation)

          -  History of allergy or hypersensitivity to salicylates, aminosalicylates, or any
             component of the Pentasa capsule.

          -  History of coexisting chronic illness or evidence of significant organic or
             psychiatric disease on medical history or physical examination, which, in the
             Investigator's opinion, would prevent participation in the study

          -  History or presence of any condition causing malabsorption or an effect on
             gastrointestinal (GI) motility, or history of extensive small bowel resection (greater
             than half the length of the small intestine).

          -  The finding of Helicobacter pylori at the time of evaluation does not exclude the
             patient from the study. Whether to treat this patient for Helicobacter pylori and when
             will be left to the discretion of the site.