Fecal Microbiota Transplant for Primary CDI

NCT03795233 | Terminated Phase 1 Results DMC FDA Drug

• 1 other identifier: H-37574
• Study Type: interventional
• Target: 5
• Locations: 1 country
• Sites: 1

Brief Summary

Clostridium difficile infection (CDI) is one of the most urgent health threats in the U.S. associated with antibiotic use. After an initial episode, disease recurrence is high and relapses can occur in 20-30% of people treated with oral vancomycin. An antibiotic course can affect the gut microbiome for years, and patients with CDI have additional dysbiosis of their gut flora. Oral vancomycin perturbs the gut microbiome further. Restoration of the microbiome with Fecal Microbiota Transplant (FMT) has been proven a highly efficacious and cost-effective treatment for recurrent CDI. FMT has had very limited study for a primary episode of CDI to date because an endoscopic procedure was the recommended route of delivery. However, FMT is now available via frozen oral capsules and has been shown to be non-inferior to FMT via colonoscopy in randomized controlled trials. The investigators hypothesize that outcomes after a first episode of CDI can be improved if the microbiome is restored with oral FMT. It is further hypothesized that this will compensate for any additional microbiome perturbation caused by administration of oral vancomycin and decrease the likelihood of recurrence. Because the hypothesis is based on restoration of the microbiome, the investigators propose this proof-of-concept pilot study to examine whether FMT administered after oral vancomycin therapy for primary CDI restores microbiome diversity compared to patients who do not receive FMT. Because of the potential health benefits, this approach deserves further study. The results from this pilot study on the microbiome diversity as well as the surveys to be conducted about GI symptomatology (e.g., diarrhea, abdominal pain, bloating), CDI recurrence and healthcare utilization, would provide preliminary data to support a randomized controlled, multicenter clinical trial.

Conditions

Clostridium Difficile Infection

Keywords

Fecal Microbiota Transplant (FMT); Vancomycin; Dysbiosis; fecal microbiome; C difficile infection

Outcome Measures

Primary Outcomes (1)

• Stool Microbiome With and Without FMT Administration

  The stool microbiome in participants who receive additional FMT at end of Clostridium difficile infection (CDI) treatment with oral vancomycin will be compared to the stool microbiome in participants with standard treatment or oral vancomycin alone

  11 months

Secondary Outcomes (5)

• Feasibility of Administering FMT After Completion of a Course of Oral Vancomycin Therapy

  12 months

• Incidence of Treatment-Emergent Adverse Events [Safety and Tolerability] of FMT After a Course of Oral Vancomycin Therapy

  During test dose, during 90 minutes of FMT administration, 30 minutes after FMT administration, 48-72 hours after FMT administration

• Incidence of Gastrointestinal Symptomatology Based on a Survey After CDI

  60 days

• CDI Recurrence

  60 days

• Number of Hospital Readmissions After Treatment

  30 days

Study Arms (2)

Fecal microbiota transplantation

EXPERIMENTAL

Fecal microbiota transplant G3 capsules will be administered after standard of care with oral vancomycin therapy in participants with primary Clostridium difficile infection.

Biological: Fecal microbiota transplant G3 capsules

Oral vancomycin alone (Control)

ACTIVE COMPARATOR

Oral vancomycin therapy will be administered as per standard of care in participants with primary clostridium difficile infection.

Other: Oral Vancomycin alone

Interventions

Fecal microbiota transplant G3 capsules BIOLOGICAL

After standard of care therapy with oral vancomycin, frozen oral FMT capsules will be provided in a formulation designed to deliver the product to the large intestine. 30 FMT capsules will be administered over a 2 hour period under direct observation

Also known as: FMT

Fecal microbiota transplantation

Oral Vancomycin alone OTHER

Standard of care will be provided with oral vancomycin therapy.

Also known as: Oral Vancocin alone

Oral vancomycin alone (Control)

Eligibility Criteria

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

You may qualify if:

• Diagnosis of primary clostridium difficile infection (CDI) defined by the presence of diarrhea and a positive C. difficile Polymerase chain reaction (PCR) test
• Admitted to Boston Medical Center
• English speaking

You may not qualify if:

• Primary CDI treatment failure
• History of CDI
• Diagnosis of inflammatory bowel disease, immunocompromised state, or active malignancy
• Dysphagia: oropharyngeal, esophageal, functional, neuromuscular (e.g. stroke, multiple sclerosis, ALS), or patient shows evidence of dysphagia when the 'safety test' capsule is administered
• History of aspiration
• History of gastroparesis
• History of intestinal obstruction
• Severe food allergy (e.g. anaphylaxis or anaphylactoid reaction) Adverse event attributable to a previous FMT
• Patients with allergies to sodium chloride, glycerol, theobroma oil, hide bovine gelatin, sodium lauryl sulfate, Food, Drugs \& Cosmetics certified colorants (FD\&C), or titanium dioxide, all ingredients Generally Recognized As Safe (GRAS)
• History of ongoing antibiotic use (e.g. nitrofurantoin for urinary tract infection (UTI) prophylaxis) Currently pregnant or breastfeeding -Any condition for which the treating physician thinks the treatment may pose a health risk (e.g. severely immunocompromised)-

Sponsors & Collaborators

• Boston Medical Center: lead

Study Sites (1)

Boston Medical Center

Boston, Massachusetts, 02118, United States

Location

MeSH Terms

Conditions

Clostridium Infections; Dysbiosis

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Limitations and Caveats

The study was terminated after a covid-related suspension and the unavailability of drug. Data were not collected for 5 of the 6 outcomes measures and no data were collected for the primary outcome measure as no participant was in the study at the timeframe of 11 months.

Results Point of Contact

• Title: Tamar Barlam, MD MSC
• Organization: Boston Medical Center

tamar.barlam@bmc.org

617 414 5190

Study Officials

• Tamar Barlam, MD MSC

  Boston Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 21, 2018
• First Posted: January 7, 2019
• Study Start: August 23, 2019
• Primary Completion: January 15, 2021
• Study Completion: January 15, 2021
• Last Updated: December 15, 2021
• Results First Posted: December 15, 2021

Record last verified: 2021-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)