Diarrhea, Lymphocytic Colitis
Conditions
Keywords
Lymphocytic Colitis, diarrhea, budesonide
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.
Interventions
OTHERPlacebo
Placebo, 3 tablets daily
DRUGBudesonide
9 mg daily (three tablets)
Sponsors
AstraZeneca
National Center for Research Resources (NCRR)
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 100 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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)). |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from Mayo Clinic, Rochester, Minnesota from June 2003 - February 2008.
Participants by arm
| Arm | Count |
|---|---|
| Budesonide 9 mg daily | 12 |
| Placebo three tablets daily | 4 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Placebo | Budesonide | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants | 12 Participants | 16 Participants |
| Age, Continuous | 59 years STANDARD_DEVIATION 12 | 56 years STANDARD_DEVIATION 19 | 58 years STANDARD_DEVIATION 13 |
| Region of Enrollment United States | 4 participants | 12 participants | 16 participants |
| Sex: Female, Male Female | 3 Participants | 10 Participants | 13 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 4 |
| serious Total, serious adverse events | 0 / 11 | 0 / 4 |
Outcome results
Primary
Satisfactory Control of Diarrhea During at Least Three of the Last Four Weeks
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.
Time frame: Three out of last four weeks that the subject was on the study
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | Satisfactory Control of Diarrhea During at Least Three of the Last Four Weeks | 11 participants |
| Placebo | Satisfactory Control of Diarrhea During at Least Three of the Last Four Weeks | 4 participants |
Secondary
Histologic Improvement in Post Treatment Colon Biopsies Compared to Baseline Biopsies
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)).
Time frame: Baseline (day 1 of study) and at eight weeks (approximately)
Population: Only 8 of the subjects on the budesonide arm returned for the biopsy, so only those subjects on that arm were analyzed for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Budesonide | Histologic Improvement in Post Treatment Colon Biopsies Compared to Baseline Biopsies | 7 participants |
| Placebo | Histologic Improvement in Post Treatment Colon Biopsies Compared to Baseline Biopsies | 1 participants |