Budesonide Versus Placebo for the Treatment of Lymphocytic Colitis

• Sponsor: Mayo Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT00217022
• Collaborator: AstraZeneca (Industry), National Center for Research Resources (NCRR) (NIH)
• Enrollment: 16
• Location: 1
• Arms: 2
• Duration (Months): 56
• Patients Per Site Per Month: 0.3

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Lymphocytic Colitis; Diarrhea	Other: Placebo; Drug: Budesonide	Phase 2/Phase 3

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-Blind, Placebo Controlled Trial of Budesonide for the Treatment of Active Lymphocytic Colitis
• Study Start Date: Jun 1, 2003
• Actual Primary Completion Date: Feb 1, 2008
• Actual Study Completion Date: Feb 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Budesonide 9 mg daily	Drug: Budesonide; 9 mg daily (three tablets); Other Names: Entocort EC
Placebo Comparator: Placebo three tablets daily	Other: Placebo; Placebo, 3 tablets daily

Outcome Measures

Primary Outcome Measures

1. 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

1. 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)).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 100 Years
• Sexes Eligible for Study: All
• Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mayo Clinic	Rochester	Minnesota	United States	55905

Sponsors and Collaborators

• Mayo Clinic
• AstraZeneca
• National Center for Research Resources (NCRR)

Investigators

• Principal Investigator: Darrell S. Pardi, M.D., Mayo Clinic

Study Documents (Full-Text)

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form - May 17, 2017

More Information

Additional Information:

• Mayo Clinic Clinical Trials

Publications

None provided.

• Responsible Party: Darrell S. Pardi, M.D., Physician, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT00217022
• Other Study ID Numbers: 1132-03; IRUSBUEN0002; UL1RR024150
• First Posted: Sep 22, 2005
• Last Update Posted: Nov 2, 2021
• Last Verified: Oct 1, 2021

• Keywords provided by Darrell S. Pardi, M.D., Physician, Mayo Clinic: Lymphocytic Colitis; diarrhea; budesonide
• Additional relevant MeSH terms: Colitis; Colitis, Lymphocytic; Diarrhea; Budesonide

Study Results

Participant Flow

Recruitment Details	Participants were recruited from Mayo Clinic, Rochester, Minnesota from June 2003 - February 2008.

Arm/Group Title	Budesonide	Placebo
Arm/Group Description	9 mg daily	three tablets daily
Period Title: Overall Study
STARTED	12	4
COMPLETED	11	3
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Budesonide	Placebo	Total
Arm/Group Description	9 mg daily	three tablets daily	Total of all reporting groups
Overall Participants	12	4	16
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	12 100%	4 100%	16 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	56 (19)	59 (12)	58 (13)
Sex: Female, Male (Count of Participants)
Female	10 83.3%	3 75%	13 81.3%
Male	2 16.7%	1 25%	3 18.8%
Region of Enrollment (participants) [Number]
United States	12 100%	4 100%	16 100%

Outcome Measures

1. Primary Outcome

Title	Satisfactory Control of Diarrhea During at Least Three of the Last Four Weeks
Description	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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Budesonide	Placebo
Arm/Group Description	9 mg daily	three tablets daily
Measure Participants	11	4
Number [participants]	11 91.7%	4 100%

2. Secondary Outcome

Title	Histologic Improvement in Post Treatment Colon Biopsies Compared to Baseline Biopsies
Description	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)

Outcome Measure Data

Analysis Population Description

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/Group Title	Budesonide	Placebo
Arm/Group Description	9 mg daily	three tablets daily
Measure Participants	8	3
Number [participants]	7 58.3%	1 25%

Adverse Events

Arm/Group Title	Budesonide		Placebo
Arm/Group Description	9 mg daily		three tablets daily
All Cause Mortality
	Budesonide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Budesonide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Budesonide		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/4 (0%)

Limitations/Caveats

Study closed early, because of low enrollment. Primary physician for patients with lymphocytic colitis would prescribe Budesonide off label for them. Subjects not interested in placebo trial.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.