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

NCT01847170 | Completed Phase 1 DMC

• 1 other identifier: 2012P000353
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

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.

Conditions

Crohn's Disease

Outcome Measures

Primary Outcomes (2)

• Safety of FMT in patients with Crohn's disease, as measured by number and nature of adverse events

  24 weeks

• Recipients' fecal microbial diversity after FMT, when compared to baseline

  12 weeks

Secondary Outcomes (9)

• Recipients' fecal microbial diversity at 4 and 8 weeks after FMT, when compared to baseline

  8 weeks

• Mean change in Harvey Bradshaw Index (HBI) score

  12 weeks

• Percentage of patients in clinical remission (those with an HBI score at week 12 <5)

  12 weeks

• Mean change in Short Inflammatory Bowel Disease Questionnaire (sIBDQ) score

  12 weeks

• Percentage of patients in endoscopic remission (CDEIS score <3)

  12 weeks

Study Arms (1)

Fecal Microbial Transplantation

EXPERIMENTAL

Biological: Fecal Microbial Transplantation

Interventions

Fecal Microbial Transplantation BIOLOGICAL

Also known as: Fecal Transplant, Stool transplant

Fecal Microbial Transplantation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Beth Israel Deaconess Medical Center: lead
• The Broad Foundation: collaborator
• Brigham and Women's Hospital: collaborator

Study Sites (1)

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Related Publications (1)

• 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.

  PMID: 27542133 DERIVED

MeSH Terms

Conditions

Crohn Disease

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Inflammatory Bowel Diseases; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Alan C Moss, MD

  Beth Israel Deaconess Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: May 2, 2013
• First Posted: May 6, 2013
• Study Start: May 1, 2013
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: March 3, 2017

Record last verified: 2017-03

Locations

US (1)