Safety of FMT: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection

• Sponsor: Microbiome Health Research Institute (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02403622
• Collaborator: Brown University (Other), Edward Hospital (Other), Indiana University (Other), Tufts Medical Center (Other)
• Enrollment: 17
• Locations: 4
• Arm: 1
• Actual Duration (Months): 39
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

The overarching objective of this study is to address the knowledge gap regarding the short-term and long-term safety of fecal microbiota transplants (FMT). The design will be a prospective, open-label, multi-center longitudinal cohort study to assess the short- and long-term safety of FMT as well as the clinical resolution of diarrhea among 150 patients with 3 or more episodes of clostridium difficile infection (CDI defined as 3 unformed stools over 24 hours for 2 consecutive days and either a positive stool test for CDI or pseudomembranes on colonoscopy/sigmoidoscopy). Subjects will be adult outpatients referred to one of the study centers after at least three recurrent episodes of CDI and previous treatment with at least one 10-day course of oral vancomycin or fidaxomicin. After FMT by colonoscopy/sigmoidoscopy or enema, patients will be followed prospectively and monitored for clinical resolution and adverse events at: 3 days (telephone), 3 weeks (clinical assessment), 8 weeks (telephone), 6 months (telephone), and 12 months (telephone) after FMT. Subjects who recur will be offered a second FMT by colonoscopy with a different donor. Microbiome analysis will be conducted from stool samples at baseline and each of the 5 follow-up intervals.

Condition or Disease	Intervention/Treatment	Phase
Clostridium Difficile	Drug: Fecal Microbiota Preparation	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety of Fecal Microbiota Transplantation: OpenBiome Outcomes and Longitudinal Follow-up (STOOL) for Recurrent Clostridium Difficile Infection
• Actual Study Start Date: Mar 1, 2015
• Actual Primary Completion Date: Oct 1, 2017
• Actual Study Completion Date: Jun 1, 2018

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Intervention: Fecal Microbiota Preparation Open label single arm Dosage form: Screened human donor stool, sourced from human-derived microbes generated by healthy, screened donors. Route of administration: either colonoscopic/sigmoidoscopic FMT or retention enema FMT Dosing Regimen: 250 mL x 1 dose. In the event of a clinical non-response, a repeat single 250 mL dose will occur from a different donor

Drug: Fecal Microbiota Preparation; Frozen processed human fecal material for treating recurrent Clostridium difficile infections.

Outcome Measures

Primary Outcome Measures

1. Short-term Safety of FMT as Measured by Absence or Presence of Related Serious Adverse Events [< 6 weeks post FMT]

   Determine the short-term safety of FMT for the prevention of further CDI recurrence. Short-term safety was measured by absence or presence of related serious adverse events

2. Long-term Safety of FMT as Measured by Absence or Presence of Adverse Events [> 6 weeks to 1 year post FMT]

   Determine the long-term safety of FMT for the prevention of further CDI recurrence

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult (age 18-75 years old)

• Outpatient

• Third or further documented CDI episode and

• Unable to maintain CDI cure after standard therapy with oral vancomycin or fidaxomicin

• Previous treatment with at least one course of tapered/pulse vancomycin or

• Inability to taper or stop vancomycin or fidaxomicin without developing diarrhea requiring antibiotic therapy.

• Improvement of CDI symptoms on vancomycin or fidaxomicin

Exclusion Criteria:

• Unable to comply with study follow-up procedures at discretion of MD

• Unable to provide informed consent at discretion of MD

• Participating in another clinical trial

• Pregnant or nursing currently or planned pregnancy in next 1 year

• Evidence of toxic megacolon or gastrointestinal perforation

• Peripheral white blood cell count >30 x 10^9/L and/or temperature >38 degrees Celsius

• Admission to an intensive care unit within prior 7 days for any reason

• Previously undergone FMT

• Severely immunocompromised patients

• HIV infection (any CD4 count)

• AIDS-defining diagnoses

• Inherited/primary immune disorder

• Immunosuppressant medications:

• Current or recent (<3 months) treatment with anti-neoplastic agents

• Current or recent (<3 months) treatment with calcineurin inhibitors (tacrolimus, cyclosporine)

• Current or recent (<3 months) treatment with mycophenolate mofetil

• Current or recent (<3 months) treatment with monoclonal antibodies to B and T-Cells, anti-TNF, glucocorticoids, antimetabolites (azathioprine, 6-mercaptopurine)

• Neutropenia with absolute neutrophil count (ANC) <0.5 x 10^9/L

• Active gastroenteritis due to infectious cause other than CDI

• Short gut syndrome

• Colostomy

• Ascites

• End-stage liver disease

• Untreated, in-situ colorectal cancer

• Irritable bowel syndrome

• Inflammatory bowel disease including Crohn's disease and ulcerative colitis

• Microscopic colitis including collagenous colitis and lymphocytic colitis

• Severe food allergy (anaphylaxis) that cannot be confirmed as having been excluded from a donor's diet within the five days prior to donation

• Anorectal disorder/severe rectal sphincter tone abnormality or inability to retain enema material

• Unable or unwilling to tolerate colonoscopy/sigmoidoscopy, colonoscopy prep, or enema for any reason at discretion of MD

• Severe underlying disease that the patient is not expected to survive for the subsequent 12 months at the discretion of the MD.

• Any conditions for which, in opinion of MD, the treatment may pose a health risk

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Edward Hospital	Naperville	Illinois	United States	60540
2	IU University Hospital	Indianapolis	Indiana	United States	46202
3	Tufts Medical Center	Boston	Massachusetts	United States	02108
4	Brown University	Providence	Rhode Island	United States	02904

Sponsors and Collaborators

• Microbiome Health Research Institute
• Brown University
• Edward Hospital
• Indiana University
• Tufts Medical Center

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 3, 2014

More Information

Publications

None provided.

• Responsible Party: Microbiome Health Research Institute
• ClinicalTrials.gov Identifier: NCT02403622
• Other Study ID Numbers: 1410006671
• First Posted: Mar 31, 2015
• Last Update Posted: Feb 23, 2021
• Last Verified: Feb 1, 2021

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Clostridium Infections

Study Results

Participant Flow

Recruitment Details	A total of 17 participants enrolled (signed consents) across four sites during the period between March 27, 2015 and October 4, 2017.
Pre-assignment Detail	Two enrolled participants withdrew from the study prior to intervention.

Arm/Group Title	Intervention: Fecal Microbiota Preparation
Arm/Group Description	Open label single arm Dosage form: Screened human donor stool, sourced from human-derived microbes generated by healthy, screened donors. Route of administration: either colonoscopic/sigmoidoscopic FMT or retention enema FMT Dosing Regimen: 250 mL x 1 dose. In the event of a clinical non-response, a repeat single 250 mL dose will occur from a different donor Fecal Microbiota Preparation: Frozen processed human fecal material for treating recurrent Clostridium difficile infections.
Period Title: Overall Study
STARTED	15
COMPLETED	13
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Intervention: Fecal Microbiota Preparation
Arm/Group Description	Open label single arm Dosage form: Screened human donor stool, sourced from human-derived microbes generated by healthy, screened donors. Route of administration: either colonoscopic/sigmoidoscopic FMT or retention enema FMT Dosing Regimen: 250 mL x 1 dose. In the event of a clinical non-response, a repeat single 250 mL dose will occur from a different donor Fecal Microbiota Preparation: Frozen processed human fecal material for treating recurrent Clostridium difficile infections.
Overall Participants	17
Age, Customized (Count of Participants)
18 to 35 years	0 0%
35 to 55 years	8 47.1%
55 to 75 years	9 52.9%
Sex: Female, Male (Count of Participants)
Female	10 58.8%
Male	7 41.2%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	17 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (Count of Participants)
United States	17 100%

Outcome Measures

1. Primary Outcome

Title	Short-term Safety of FMT as Measured by Absence or Presence of Related Serious Adverse Events
Description	Determine the short-term safety of FMT for the prevention of further CDI recurrence. Short-term safety was measured by absence or presence of related serious adverse events
Time Frame	< 6 weeks post FMT

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intervention: Fecal Microbiota Preparation
Arm/Group Description	Open label single arm Dosage form: Screened human donor stool, sourced from human-derived microbes generated by healthy, screened donors. Route of administration: either colonoscopic/sigmoidoscopic FMT or retention enema FMT Dosing Regimen: 250 mL x 1 dose. In the event of a clinical non-response, a repeat single 250 mL dose will occur from a different donor Fecal Microbiota Preparation: Frozen processed human fecal material for treating recurrent Clostridium difficile infections.
Measure Participants	15
Count of Participants [Participants]	0 0%

2. Primary Outcome

Title	Long-term Safety of FMT as Measured by Absence or Presence of Adverse Events
Description	Determine the long-term safety of FMT for the prevention of further CDI recurrence
Time Frame	> 6 weeks to 1 year post FMT

Outcome Measure Data

Analysis Population Description

Data were not collected therefore could not be reported.

Arm/Group Title	Intervention: Fecal Microbiota Preparation
Arm/Group Description	Open label single arm Dosage form: Screened human donor stool, sourced from human-derived microbes generated by healthy, screened donors. Route of administration: either colonoscopic/sigmoidoscopic FMT or retention enema FMT Dosing Regimen: 250 mL x 1 dose. In the event of a clinical non-response, a repeat single 250 mL dose will occur from a different donor Fecal Microbiota Preparation: Frozen processed human fecal material for treating recurrent Clostridium difficile infections.
Measure Participants	0

Adverse Events

Time Frame	As outlined in the protocol, safety data were collected up to 12 months post-FMT. Due to study termination, not all participants were followed for the full 12 months, but instead an average of 11.7 months.
Arm/Group Title	Intervention: Fecal Microbiota Preparation
Arm/Group Description	Open label single arm Dosage form: Screened human donor stool, sourced from human-derived microbes generated by healthy, screened donors. Route of administration: either colonoscopic/sigmoidoscopic FMT or retention enema FMT Dosing Regimen: 250 mL x 1 dose. In the event of a clinical non-response, a repeat single 250 mL dose will occur from a different donor Fecal Microbiota Preparation: Frozen processed human fecal material for treating recurrent Clostridium difficile infections.
All Cause Mortality
	Intervention: Fecal Microbiota Preparation
	Affected / at Risk (%)	# Events
Total	0/15 (0%)
Serious Adverse Events
	Intervention: Fecal Microbiota Preparation
	Affected / at Risk (%)	# Events
Total	4/15 (26.7%)
Cardiac disorders
Atrial fibrillation	1/15 (6.7%)	1
Tachycardia	1/15 (6.7%)	1
Endocrine disorders
Hyperthyroidism	1/15 (6.7%)	1
Gastrointestinal disorders
Abdominal pain	1/15 (6.7%)	1
Constipation	1/15 (6.7%)	1
Intestinal ischaemia	1/15 (6.7%)	1
Irritable bowel syndrome	1/15 (6.7%)	1
Vomiting	1/15 (6.7%)	1
Infections and infestations
Urinary tract infection	2/15 (13.3%)	2
Metabolism and nutrition disorders
Dehydration	1/15 (6.7%)	1
Hypokalaemia	1/15 (6.7%)	1
Hypomagnesaemia	1/15 (6.7%)	1
Nervous system disorders
Embolic stroke	1/15 (6.7%)	1
Surgical and medical procedures
Gastrectomy	1/15 (6.7%)	1
Pancreatectomy	1/15 (6.7%)	1
Splenectomy	1/15 (6.7%)	1
Other (Not Including Serious) Adverse Events
	Intervention: Fecal Microbiota Preparation
	Affected / at Risk (%)	# Events
Total	14/15 (93.3%)
Cardiac disorders
Tachycardia	1/15 (6.7%)	1
Gastrointestinal disorders
Abdominal Pain	7/15 (46.7%)	8
Bloating/Distention	2/15 (13.3%)	2
Constipation	3/15 (20%)	7
Diarrhea	5/15 (33.3%)	5
Flatulence	6/15 (40%)	8
Nausea	1/15 (6.7%)	1
Increase in bowel movements	1/15 (6.7%)	1
Incontinence	1/15 (6.7%)	1
General disorders
Fatigue and malaise	1/15 (6.7%)	1
Immune system disorders
Allergies	1/15 (6.7%)	1
Infections and infestations
UTI	5/15 (33.3%)	6
CDI	1/15 (6.7%)	1
Injury, poisoning and procedural complications
5th Metatarsal fracture	1/15 (6.7%)	1
Metabolism and nutrition disorders
Weight gain	1/15 (6.7%)	1
Weight loss	1/15 (6.7%)	1
Thyrotoxicosis	1/15 (6.7%)	1
Dehydration	1/15 (6.7%)	1
Hypokalemia	1/15 (6.7%)	1
Graves' Disease	1/15 (6.7%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cancer	1/15 (6.7%)	1
Psychiatric disorders
Anxiety	1/15 (6.7%)	1
Surgical and medical procedures
Knee Replacement	1/15 (6.7%)	1
Laparoscopy	1/15 (6.7%)	1
Vascular disorders
Stroke	1/15 (6.7%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.