Clotrimazole Enemas for Pouchitis in Children and Adults
Information source: FDA Office of Orphan Products Development
Information obtained from ClinicalTrials.gov on October 19, 2009
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Ulcerative Colitis; Pouchitis; Ileitis; Inflammatory Bowel Disease
Intervention: Clotrimazole (Drug)
Phase: Phase 1/Phase 2
Status: Recruiting
Sponsored by: FDA Office of Orphan Products Development Official(s) and/or principal investigator(s):
Paul A. Rufo, MD, MMSc, Principal Investigator, Affiliation: Children's Hospital and Harvard Medical School
Overall contact:
Paul A. Rufo, MD, MMSc, Phone: 617-355-6058, Email: paul.rufo@tch.harvard.edu
Summary
Colectomy with creation of an ileal pouch (IPAA) is now the treatment of choice for patients
with ulcerative colitis that is resistant to existing medical therapies. The development of
inflammation in these ileal reservoirs, a clinical entity referred to as pouchitis, is the
most common long-term complication of this procedure and can affect 50-60% of adults and
children. We have previously demonstrated that clotrimazole (delivered as a rectal
suppository) is generally safe, effective, and displays poor systemic absorption when used
in pediatric and adults with active pouchitis. We saw clinical benefit in patients with
pouch disease that had previously failed to respond to standard antibiotic, steroid, or
immunosuppressive therapies. The clinical trial outlined here will define the effectiveness
and safety of topical clotrimazole therapy (delivered as a rectal enema) in pediatric (aged
greater than two years) and adult patients with pouchitis.
Subjects in this study will be randomly assigned to receive either placebo (no active drug,
4 subjects) or one of two clotrimazole therapy groups: 2500 mg/day (8 subjects) or
4000mg/day (8 subjects). No washout period is required, and subjects will be allowed to
continue their existing anti-inflammatory medications during their participation in the
study. Clotrimazole will be delivered nightly in the form of an enema. Subjects will
undergo flexible sigmoidoscopy (pouchoscopy) prior to and again after completing one month
of study therapy, and pouch disease activity will be graded at after each procedure using
the Pouchitis Disease Activity Index (PDAI). Clinical improvement will be defined as a drop
in PDAI score. If the drop in PDAI scores between placebo and either active clotrimazole
treatment group is not significant, and no subject experiences what are determined to be
study-related adverse effects, a second cohort of subjects will be recruited and studied
after receiving one month of either placebo (4 subjects), 6000 mg/day clotrimazole (8
subjects), or 7500mg/day clotrimazole (8 subjects).
Subjects will be assessed for adverse effects at the midpoint of the study. Clotrimazole
blood levels will be measured during the first and last day of study participation. In
addition, adults will complete a health related quality of life assessment at baseline and
after completing study drug therapy.
All subjects will be eligible for one month of open-label study drug therapy after
completing one month of study drug therapy.
Clinical Details
Official title: Clotrimazole Enemas for Pouchitis in Children and Adults
Study design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Primary outcome: Improvement in Pouchitis Disease Activity Index (PDAI)
Eligibility
Minimum age: 2 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
- Age greater than 2 years
- Availability of Parent or Legal Guardian (for those less than 2 years of age).
- History of ulcerative colitis treated with colectomy and ileal pouch
- Diagnosis of acute or chronic pouchitis
Locations and Contacts
Paul A. Rufo, MD, MMSc, Phone: 617-355-6058, Email: paul.rufo@tch.harvard.edu
Children's Hospital, Boston, Massachusetts 02115, United States; Recruiting
Paul A. Rufo, MD, MMSc, Phone: 617-355-6058, Email: paul.rufo@tch.harvard.edu
Thomas R. Walker, MD, Phone: 617-355-6256, Email: thomas.walker@tch.harvard.edu
Paul A. Rufo, MD, MMSc, Principal Investigator
Thomas R. Walker, M.D., Sub-Investigator
Alan Leichtner, M.D., Sub-Investigator
Additional Information
Crohn's and Colitis Foundation of America
Starting date: September 2002
Ending date: June 2008
Last updated: September 19, 2007
|
