- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01847170
Impact of Fecal Biotherapy (FBT) on Microbial Diversity in Patients With Moderate to Severe Inflammatory Bowel Disease
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.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
Massachusetts
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Boston, Massachusetts, United States, 02215
- Beth Israel Deaconess Medical Center
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Basic Science
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Fecal Microbial Transplantation
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Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events
Time Frame: 24 weeks
|
24 weeks
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Recipients' fecal microbial diversity after FMT, when compared to baseline
Time Frame: 12 weeks
|
12 weeks
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline
Time Frame: 8 weeks
|
8 weeks
|
Mean change in Harvey Bradshaw Index (HBI) score
Time Frame: 12 weeks
|
12 weeks
|
Percentage of patients in clinical remission (those with an HBI score at week 12 <5)
Time Frame: 12 weeks
|
12 weeks
|
Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score
Time Frame: 12 weeks
|
12 weeks
|
Percentage of patients in endoscopic remission (CDEIS score <3)
Time Frame: 12 weeks
|
12 weeks
|
Percentage of patients with mucosal healing (CDEIS score <1)
Time Frame: 12 weeks
|
12 weeks
|
Mean change in CRP levels
Time Frame: 12 weeks
|
12 weeks
|
Mean change in Crohn's Disease Endoscopic Index of Severity (CDEIS) score
Time Frame: 12 weeks
|
12 weeks
|
Tolerability score
Time Frame: 2 weeks
|
2 weeks
|
Collaborators and Investigators
Investigators
- Principal Investigator: Alan C Moss, MD, Beth Israel Deaconess Medical Center
Publications and helpful links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2012P000353
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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