Impact of Fecal Biotherapy (FBT) on Microbial Diversity in Patients With Moderate to Severe Inflammatory Bowel Disease
Primary Purpose
Crohn's Disease
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Fecal Microbial Transplantation
Sponsored by
About this trial
This is an interventional basic science trial for Crohn's Disease
Eligibility Criteria
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
Sites / Locations
- Beth Israel Deaconess Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Fecal Microbial Transplantation
Arm Description
Outcomes
Primary Outcome Measures
Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events
Recipients' fecal microbial diversity after FMT, when compared to baseline
Secondary Outcome Measures
Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline
Mean change in Harvey Bradshaw Index (HBI) score
Percentage of patients in clinical remission (those with an HBI score at week 12 <5)
Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score
Percentage of patients in endoscopic remission (CDEIS score <3)
Percentage of patients with mucosal healing (CDEIS score <1)
Mean change in CRP levels
Mean change in Crohn's Disease Endoscopic Index of Severity (CDEIS) score
Tolerability score
Full Information
NCT ID
NCT01847170
First Posted
May 2, 2013
Last Updated
March 2, 2017
Sponsor
Beth Israel Deaconess Medical Center
Collaborators
The Broad Foundation, Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT01847170
Brief Title
Impact of Fecal Biotherapy (FBT) on Microbial Diversity in Patients With Moderate to Severe Inflammatory Bowel Disease
Study Type
Interventional
2. Study Status
Record Verification Date
March 2017
Overall Recruitment Status
Completed
Study Start Date
May 2013 (undefined)
Primary Completion Date
November 2016 (Actual)
Study Completion Date
November 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Beth Israel Deaconess Medical Center
Collaborators
The Broad Foundation, Brigham and Women's Hospital
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief 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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Crohn's Disease
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Fecal Microbial Transplantation
Arm Type
Experimental
Intervention Type
Biological
Intervention Name(s)
Fecal Microbial Transplantation
Other Intervention Name(s)
Fecal Transplant, Stool transplant
Primary Outcome Measure Information:
Title
Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events
Time Frame
24 weeks
Title
Recipients' fecal microbial diversity after FMT, when compared to baseline
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline
Time Frame
8 weeks
Title
Mean change in Harvey Bradshaw Index (HBI) score
Time Frame
12 weeks
Title
Percentage of patients in clinical remission (those with an HBI score at week 12 <5)
Time Frame
12 weeks
Title
Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score
Time Frame
12 weeks
Title
Percentage of patients in endoscopic remission (CDEIS score <3)
Time Frame
12 weeks
Title
Percentage of patients with mucosal healing (CDEIS score <1)
Time Frame
12 weeks
Title
Mean change in CRP levels
Time Frame
12 weeks
Title
Mean change in Crohn's Disease Endoscopic Index of Severity (CDEIS) score
Time Frame
12 weeks
Title
Tolerability score
Time Frame
2 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alan C Moss, MD
Organizational Affiliation
Beth Israel Deaconess Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beth Israel Deaconess Medical Center
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
27542133
Citation
Vaughn BP, Vatanen T, Allegretti JR, Bai A, Xavier RJ, Korzenik J, Gevers D, Ting A, Robson SC, Moss AC. Increased Intestinal Microbial Diversity Following Fecal Microbiota Transplant for Active Crohn's Disease. Inflamm Bowel Dis. 2016 Sep;22(9):2182-90. doi: 10.1097/MIB.0000000000000893.
Results Reference
derived
Learn more about this trial
Impact of Fecal Biotherapy (FBT) on Microbial Diversity in Patients With Moderate to Severe Inflammatory Bowel Disease
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