Budesonide Versus Placebo for the Treatment of Lymphocytic Colitis

Phase 2

Terminated

Brief Summary: Patients will receive budesonide or placebo for the treatment of active lymphocytic colitis. This study includes stool collections, blood draws, weekly questionnaires and a sigmoidoscopy. The study hypothesis is that budesonide will be safe and effective compared with placebo for the treatment of diarrhea in lymphocytic colitis.

Detailed Description: Microscopic colitis is an increasingly diagnosed cause of chronic diarrhea, with two main subtypes: collagenous and lymphocytic colitis. Uncontrolled reports have suggested that various drugs can be beneficial in treating microscopic colitis, but few treatments have been evaluated in randomized controlled trials. Thus, treatment is guided mostly by anecdotal reports, case series, and physicians' experience. In our uncontrolled experience, corticosteroids are one of the most effective therapies for microscopic colitis, but are not typically used as a first line therapy because of toxicity. Budesonide has been reported to be of clinical benefit in small, uncontrolled series of patients with microscopic colitis, and recent controlled trials showed that it is superior to placebo in collagenous colitis. We propose a study of budesonide in patients with the lymphocytic type of microscopic colitis.

Patients will have stool specimen and blood drawn at the start of the study. Patient will take either Budesonide or placebo for 8 weeks. At the end of treatment, patient will have stool collection and sigmoidoscopy.

Recruitment & Eligibility

Inclusion Criteria

Diarrhea, defined as greater than 4 bowel movements per day and greater than "mild"; currently on no treatment or active despite treatment.
Lymphocytic colitis confirmed histologically within one year of enrollment

Exclusion Criteria

Previous unsuccessful treatment with corticosteroids or immunosuppressive drugs
History of severe corticosteroid side effects
Corticosteroid, ticlopidine, or flutamide use within the previous 4 weeks
Antibiotic, mesalamine or bismuth subsalicylate use within two weeks
Current use of anticholinergics, cholestyramine, narcotics, ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, or grapefruit juice
Known active medical conditions, including cancer, infection, uncontrolled hypertension or diabetes, osteoporosis, peptic ulcer disease, glaucoma, cataracts, liver cirrhosis or history of tuberculosis
Other diarrheal conditions (sprue, infection, hyperthyroidism, lactose intolerance)
Pregnant or nursing females
Patients without a telephone or unable to communicate in English over the telephone, or unable or unwilling to give consent
Known hypersensitivity to or intolerance of budesonide.

Arm && Interventions

Group	Intervention	Description
Budesonide	Budesonide	9 mg daily
Placebo	Placebo	three tablets daily

Primary Outcome Measures

Name	Time	Method
Satisfactory Control of Diarrhea During at Least Three of the Last Four Weeks	Three out of last four weeks that the subject was on the study	Subjects were asked if they felt they had satisfactory control of their diarrhea, along with the number of stools and type of stool (loose, water, formed, hard) the patient were experiencing. The rating of "satisfactory control" of diarrhea was therefore a partially subjective measure. This outcome measure was to be recorded for three out of the last four weeks that a subject was on the study; subjects were to take part in the study approximately 8 weeks.

Secondary Outcome Measures

Name	Time	Method
Histologic Improvement in Post Treatment Colon Biopsies Compared to Baseline Biopsies	Baseline (day 1 of study) and at eight weeks (approximately)	The histopathology scoring system included epithelial damage, lamina propria cellularity and intraepithelial lymphocytosis, each scored on a four point scale ("normal" (0), "mildly increased" (1), "moderately increased" (2), "severely increased" (3)).