Impact of Fecal Biotherapy (FBT) on Microbial Diversity in Patients With Moderate to Severe Inflammatory Bowel Disease

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
Broad Foundation
Brigham and Women's Hospital
Information provided by (Responsible Party):
Alan C. Moss, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier:
NCT01847170
First received: May 2, 2013
Last updated: August 14, 2014
Last verified: August 2014
  Purpose

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.


Condition Intervention Phase
Crohn's Disease
Biological: Fecal Microbial Transplantation
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science

Resource links provided by NLM:


Further study details as provided by Beth Israel Deaconess Medical Center:

Primary Outcome Measures:
  • Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events [ Time Frame: 24 weeks ] [ Designated as safety issue: Yes ]
  • Recipients' fecal microbial diversity after FMT, when compared to baseline [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline [ Time Frame: 8 weeks ] [ Designated as safety issue: No ]
  • Mean change in Harvey Bradshaw Index (HBI) score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients in clinical remission (those with an HBI score at week 12 <5) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients in endoscopic remission (CDEIS score <3) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Percentage of patients with mucosal healing (CDEIS score <1) [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Mean change in CRP levels [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Mean change in Crohn's Disease Endoscopic Index of Severity (CDEIS) score [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  • Tolerability score [ Time Frame: 2 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment: 20
Study Start Date: May 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Fecal Microbial Transplantation Biological: Fecal Microbial Transplantation
Other Names:
  • Fecal Transplant
  • Stool transplant

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01847170

Locations
United States, Massachusetts
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
Sponsors and Collaborators
Beth Israel Deaconess Medical Center
Broad Foundation
Brigham and Women's Hospital
Investigators
Principal Investigator: Alan C Moss, MD Beth Israel Deaconess Medical Center
  More Information

No publications provided

Responsible Party: Alan C. Moss, Associate Professor of Medicine, Beth Israel Deaconess Medical Center
ClinicalTrials.gov Identifier: NCT01847170     History of Changes
Other Study ID Numbers: 2012P-000353
Study First Received: May 2, 2013
Last Updated: August 14, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Crohn Disease
Inflammatory Bowel Diseases
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Intestinal Diseases

ClinicalTrials.gov processed this record on August 28, 2014