Predicting Response to Standardized Pediatric Colitis Therapy: The PROTECT Study

Study ID
STU 042012-017

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Takiyah Wilson
214-456-9238
takiyah.wilson@childrens.com

Principal Investigator
Ashish Patel

Summary

This multicenter open-label study is designed to evaluate the safety and efficacy of standardized initial therapy using either mesalamine or corticosteroids then mesalamine for the treatment of children and adolescents newly diagnosed with ulcerative colitis. The study will investigate the hypothesis that response to the initial 4 weeks of therapy as well as specific clinical, genetic, and immune parameters determined during the initial course of
therapy will predict severe disease as reflected by need for escalation of medical therapy or surgery. a total of 430 subjects will be assigned to one of two initial therapeutic plans (mesalamine only or prednisone followed by mesalamine) depending upon initial disease severity determined by the validated multi-dimensional Pediatric ulcerative Colitis activity index (PuCai). Biospecimens (blood, stool, colonic tissue) will be obtained at diagnosis, and subsequently following the initiation of therapy at weeks 4, 12, and 52 (blood and stool at weeks 4 and 12; blood, stool, and colonic tissue at week 52). Clinical evaluation will take place at pre-specified time points over up to two to five years of follow up. The primary endpoint is corticosteroid free remission (SFR) at 52 weeks on mesalamine therapy only without the need for rescue therapy with immunomodulators (iM), calcineurin
inhibitors (Ci), anti-TnF[RegisteredTM] therapy, or surgery. Secondary endpoints include steroid free remission (SFR) at other time points, PuCai[Less Than]10 at 4 weeks, colectomy during follow-up, quality of life measures and, in a subset of patients, endoscopic remission or response at 52 weeks.

Participant Eligibility


* 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). 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.