Early FMT for C.Difficile

NCT02465463 | Completed Phase 1 Results DMC

• 1 other identifier: IRB00077804
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

Brief Summary

Clostridium difficile infection (CDI) has increased worldwide in both frequency and severity. It is the leading cause of hospital acquired infection in developed countries and has been associated with at least 14,000 deaths per year in the United States. With 3 million cases/ year, the annual cost for treating the infection is exceeding 3 billion dollars. It can also have a profound negative impact on quality of life. The investigators believe that patients who are at high risk of relapse after a first CDI episode would benefit from early fecal microbial transplant (FMT). The proposed study will produce preliminary data regarding safety and efficacy and potential for cost effectiveness for the use of early fecal transplant in those patients with their first episode of non-refractory CDI who are predicted to have a high rate of recurrence based on previously published risk factors. The investigators will be better prepared to test the efficacy of this approach in a future multicenter clinical trial in a randomized controlled fashion. The purpose of this study is to compare the effectiveness and safety of early fecal transplant using donor stool from a healthy person in a group of patients who are diagnosed with their first episode of Clostridium difficile infection and are predicted to have a high chance of the infection returning against a similar group of patients who receive current standard of care for treatment of C.difficile. The investigators hypothesize:

• that clinical remission rates at 12 weeks as noted by absence of clinical symptoms and/or negative C.difficile stool polymerase chain reaction (PCR) will be greater in the experimental arm compared to the control arm
• that patients in the experimental group will have a low microbial diversity prior to FMT but will exhibit a high microbial diversity after the FMT that resembles the respective donor
• that the microbial diversity will be diminished in both groups at the time of enrollment, but the experimental group will exhibit a higher microbial diversity compared to the control population at 12 weeks
• that patients in both groups will exhibit poor quality of life at the time of enrollment, however, the experimental group will demonstrate higher quality of life compared to the control group at follow up after completion of treatment
• that costs incurred by the experimental group will be less than the control group

Conditions

Clostridium Difficile

Keywords

fecal microbiota transplant; probiotic

Outcome Measures

Primary Outcomes (3)

• Clinical Remission Rates

  Clinical remission rate is defined as the number of participants with an absence of clinical symptoms and/or negative C.difficile stool PCR.

  Post-Intervention (Week 12)

• Number of Participants That Experience Serious Adverse Events

  A serious adverse event is any adverse experience that results in any of the following outcomes: * Death; * Life-threatening experience (adverse event is considered "life-threatening" if, in the view of either the investigator or sponsor, its occurrence places the patient or subject at immediate risk of death); * Requires inpatient hospitalization or prolongation of existing hospitalization; * Results in persistent or significant disability or incapacity; * Is a congenital anomaly or birth defect; * Is considered to be an important medical event (that may not be immediately life threatening or result in death or hospitalization but may jeopardize the patient or may require intervention to prevent one of the outcomes listed in the definition above).

  Post-Intervention (Month 6)

• Change in the Shannon Diversity Index

  The Shannon Diversity Index is a quantitative measure that reflects how many different types (such as species) there are in a dataset (a community). 16s ribosomal gene sequencing and metabolomic profile of the gut microbiota were analyzed for both groups using the Shannon Diversity index (H). The greater the index, the more diverse a species.

  Baseline, Post-Intervention (Week 12)

Secondary Outcomes (3)

• Mean Short Form - 36 (SF-36) Score

  Post-Intervention (Week 12)

• Mean Hospital Anxiety And Depression Scale (HADS) Score

  Post-Intervention (Week 12)

• Mean Cost of Treatment

  Post-Intervention (Month 6)

Study Arms (2)

FMT arm

EXPERIMENTAL

Patients in the experimental arm with undergo a fecal microbiota transplant (FMT) after finishing a course of antibiotics.

Procedure: Fecal microbiota transplant (FMT); Device: flexible sigmoidoscopy

Control

NO INTERVENTION

Patients in the non-interventional group will not receive a FMT but will be followed over the course of 6 months to assess for recurrence of C.difficile.

Interventions

Fecal microbiota transplant (FMT) PROCEDURE

250 mL of donor stool will be infused into the colon by flexible sigmoidoscopy

FMT arm

flexible sigmoidoscopy DEVICE

FMT arm

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients must meet all of the following criteria to be eligible for the study:
• First or second episode of CDI responding to therapy
• Must have 2 or more of the following criteria:
• Age \>65
• Severe underlying disease (measured by Horn index score of 3 or 4)
• Additional non-C.difficile antibiotic exposure during CDI episode
• Use of antacids
• Previous episode of CDI
• Willingness to accept a fecal product made using unrelated donor stool and to comply with study protocol requirements
• Able to give informed consent
• Chronic infection with HIV, HBV, HCV is permitted unless the viral infection compromises the ability of the patient to safely participate in the study. Patients with a CD4 count \<200 and/ or AIDS defining illness or decompensated cirrhosis will not be eligible for the study.
• Life expectancy \>4 months

You may not qualify if:

• Any of the following: acute leukemia, history of allogenic or recent (within 6 months) autologous bone marrow transplant, or use of cytotoxic chemotherapy within 2 months
• ANC \<1000/mm\^3
• History of inflammatory bowel disease
• History of total colectomy
• Pregnant or nursing mothers
• History of significant food allergy to foods not excluded from the donor diet
• Patient has any other condition that, in the opinion of the Investigator, would jeopardize the safety or rights of the subject participating in the study, would make it unlikely for the subject to complete the study, or would confound the results of the study
• Patients who are aged 80 years or greater
• Patients who are incarcerated
• Patient with cognitive impairment or severe neuropsychiatric co morbidities who are incapable of giving consent
• Inherited/primary immune disorders
• Patients who are unwilling or unable to undergo sigmoidoscopy
• Unable to comply with protocol requirements
• Patients with untreated, in-situ colorectal cancer

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory University

Atlanta, Georgia, 30322, United States

Location

MeSH Terms

Interventions

Fecal Microbiota Transplantation

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Results Point of Contact

• Title: Dr. Tanvi Dhere
• Organization: Emory

tdhere@emory.edu

404-686-1000

Study Officials

• Tanvi Dhere, MD

  Emory University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: November 27, 2014
• First Posted: June 8, 2015
• Study Start: June 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: November 1, 2016
• Last Updated: January 31, 2018
• Results First Posted: January 31, 2018

Record last verified: 2018-01

Locations

US (1)