Treatment of Crohn's Disease With an Antibiotic Regimen Directed Against Mycobacterium Avium Paratuberculosis

Crohn's disease is a chronic inflammatory disorder of the gastrointestinal tract. The origin of Crohn's disease remains unknown and there is no curative therapy, either medical or surgical, for this gut disorder.

It is believed that an infectious agent is important in the development of Crohn's disease. The similarity of Crohn's disease to the animal form of ileitis, termed Johne's disease, supports the possibility that both disorders are caused by exposure to Mycobacterium avium paratuberculosis or MAP. Multiple investigators have demonstrated good clinical responses of patients with Crohn's disease to treatment with triple antibiotic therapy directed against mycobacterial infection.

The hypothesis of this protocol is that triple antibiotic therapy is useful as a medical therapy for patients with Crohn's disease. The aim of this study is to examine the response of patients with Crohn's disease who are not receiving therapy with biological agents to triple antibiotic therapy.

Study Overview

• Status: Withdrawn
• Conditions: Crohn's Disease
• Intervention / Treatment: Drug: Rifabutin, Clarithromycin, and Clofazimine

Detailed Description

Clinical remission will be determined by a decline in the Crohns disease activity index to <151; clinical improvement will be examined using the inflammatory bowel disease (IBD) quality of life questionnaire; and endoscopic improvement will be examined using a Crohn's disease endoscopic activity index. All individuals must have had colonoscopy within 3 months of enrollment. An estimated 20 individuals will be enrolled in this protocol. Each patient will be treated for 6 months with a combination of rifabutin, clarithromycin, and clofazimine. At the end of 6 months of treatment for each patient, the Crohns disease activity index will be recalculated, each patient will again complete the IBD quality of life questionnaire, and each patient will undergo repeat colonoscopy.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• This study will only include patients capable of providing informed consent, ages 18 and older.
• Patients must have a documented diagnosis of Crohn's disease and have had a colonoscopy with photographs within 3 months prior to randomization.
• All patients must have a CDAI of 220 or greater at enrollment.
• All females must be post-menopausal, surgically sterilized, or either abstain from sexual intercourse or use a non-hormonal method of birth control other than or in addition to oral contraceptive during the study and for 6 weeks after the end of the study.

Exclusion Criteria:

• Any patient with ulcerative colitis
• All women of child-bearing age must have a negative urine pregnancy test within 1 week prior to the initial clinic visit.
• Patients receiving a biological therapy for Crohn's disease including remicade
• Patients with a known allergy to any of the three antibiotics used in this protocol.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Antibiotics	Drug: Rifabutin, Clarithromycin, and Clofazimine; Rifabutin 150 mg by mouth twice daily, Clarithromycin 250 mg by mouth twice a day, and Clofazimine 100 mg by mouth each morning

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical remission by a decline in Crohns disease activity index to <151	Percent <151	6 Months
Clinical improvement using inflammatory bowel disease quality of life questionnaire	Improvement in QOL life questionnaire	6 Months
Endoscopic improvement using Crohn's disease endoscopic activity index	Endoscopic appearance	6 Months

Collaborators and Investigators

• Sponsor: Medstar Health Research Institute
• Investigators: Principal Investigator: Timothy R Koch, MD, MedStar Health Research Institute

Publications and helpful links

General Publications

• Karp SM, Koch TR, Pang G. Is there a MAP (Mycobacterium Avium Subspecies Paratuberculosis) for treating Crohn's disease? Practical Gastroenterology 31(4):40-50, 2007.

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2007
• Primary Completion (Actual): July 1, 2007
• Study Completion (Actual): July 1, 2007

Study Registration Dates

• First Submitted: August 6, 2007
• First Submitted That Met QC Criteria: August 7, 2007
• First Posted (Estimate): August 8, 2007

Study Record Updates

• Last Update Posted (Actual): August 20, 2020
• Last Update Submitted That Met QC Criteria: August 18, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Infections; Gastrointestinal Diseases; Gastroenteritis; Intestinal Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Inflammatory Bowel Diseases; Mycobacterium Infections, Nontuberculous; Crohn Disease; Mycobacterium avium-intracellulare Infection; Paratuberculosis; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Leprostatic Agents; Protein Synthesis Inhibitors; Antitubercular Agents; Antibiotics, Antitubercular; Rifabutin; Clarithromycin; Clofazimine
• Other Study ID Numbers: 2006-257; FDA IND 75,897