Overview

This trial is active, not recruiting.

Condition crohn's disease
Treatment fecal microbial transplantation
Phase phase 1
Sponsor Beth Israel Deaconess Medical Center
Collaborator The Broad Foundation
Start date May 2013
End date November 2016
Trial size 20 participants
Trial identifier NCT01847170, 2012P-000353

Summary

The human immune system is usually tolerant of the millions of beneficial commensal bacteria (the microbiome), which colonize the healthy intestinal tract. In contrast, patients with Inflammatory Bowel Disease (IBD) may play host to an imbalanced mix of such intestinal bacteria, which initiates abnormal immune responses in susceptible individuals. The resulting inflammation that occurs in the gastrointestinal tract damages the intestinal lining, leading to symptoms (such as intractable diarrhea, pain or weight loss), heightened cancer risk, other serious complications with substantial morbidity and even death. Current therapies for IBD focus on suppressing the excessive immune response to these bacteria, but have major side effects and do not address any role of the microbiome in disease development.

The investigators hypothesize that there is heightened intraluminal generation of pro-inflammatory factors by luminal "pathogenic" bacteria, such as extracellular nucleotides and purinergic derivatives, which trigger host immune cells. This results in loss of suppressive T regulatory cells with unrestrained immune cell deviation to pathogenic T helper cells that cause inflammatory responses. The investigators' proposal is that correcting the disease-provoking microbiome would beneficially improve gut microbial diversity, alter immune responses elicited in patients by such microbial products of pathogenic bacteria, and ultimately limit and suppress disease activity.

To test the hypothesis, the investigators propose to enroll patients with active Crohn's Disease, and introduce the microbiome of healthy and unrelated individuals to patient's intestinal tract, via fecal biotherapy (FBT) with all applicable safety measures. The investigators propose to comprehensively test the effects of FBT on the host microbiome, determine microbial production of inflammatory nucleotides and derivatives, which the investigators suggest might impact the host immune response and disease activity in patients with IBD.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Endpoint classification safety study
Intervention model single group assignment
Masking open label
Primary purpose basic science
Arm
(Experimental)
fecal microbial transplantation Fecal Transplant

Primary Outcomes

Measure
Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events
time frame: 24 weeks
Recipients' fecal microbial diversity after FMT, when compared to baseline
time frame: 12 weeks

Secondary Outcomes

Measure
Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline
time frame: 8 weeks
Mean change in Harvey Bradshaw Index (HBI) score
time frame: 12 weeks
Percentage of patients in clinical remission (those with an HBI score at week 12 <5)
time frame: 12 weeks
Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score
time frame: 12 weeks
Percentage of patients in endoscopic remission (CDEIS score <3)
time frame: 12 weeks
Percentage of patients with mucosal healing (CDEIS score <1)
time frame: 12 weeks
Mean change in CRP levels
time frame: 12 weeks
Mean change in Crohn's Disease Endoscopic Index of Severity (CDEIS) score
time frame: 12 weeks
Tolerability score
time frame: 2 weeks

Eligibility Criteria

Male or female participants at least 18 years old.

Inclusion Criteria (Patients): - CD confirmed by biopsy for > 3 months duration - Active disease (Harvey-Bradshaw Index > 5 - Failed standard therapy with; stable doses of 5-ASA >2 weeks; thiopurines >3 months; or is steroid dependent at a dose <20mg/d; (inability to taper off steroid for longer than 1 week) - Stable medication regimen for >2 weeks. - Age > 18 years old Exclusion Criteria (Patients): - Diagnosis of indeterminate colitis, or proctitis alone - Severe or fulminate colitis - Women who are pregnant or nursing - Patients who are unable to give informed consent - Patients who are unable or unwilling to undergo colonoscopy with moderate sedation (>ASA class II) - Patients who have previously undergone FMT - Patients who have a confirmed malignancy or cancer - Patients who are immunocompromised - Treatment within last 12 weeks with cyclosporine, tacrolimus, infliximab, adalimumab, certolizumab, natalizumab, thalidomide - Antibiotic use within 2-months of start date - Participation in a clinical trial in the preceding 30 days or simultaneously during this trial - Probiotic use within 30 days of start date - Rectal therapy within 14 days of start date - Decompensated cirrhosis - Congenital or acquired immunodeficiencies - Other comorbidities including: - Diabetes mellitus, cancer, systemic lupus, must be able to tolerate conscious sedation with colonoscopy - Chronic kidney disease as defined by a GFR <60mL/min/1.73m2 44 - History of rheumatic heart disease, endocarditis, or valvular disease due to risk of bacteremia from colonoscopy - Steroid dose >20mg/day

Additional Information

Principal investigator Alan C Moss, MD
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Beth Israel Deaconess Medical Center.