Fecal Microbiota Transplantation in HIV (FMT-HIV)

May 2, 2017 updated by: Ma Somsouk, MD, MAS, University of California, San Francisco

Reconstitution of the Gut Microbiome to Reduce HIV-Associated Inflammation

Even in individuals treated for HIV, chronic immune activation persists and is associated with increased cardiovascular disease, liver disease, and mortality. HIV-infected individuals have imbalances in the community of intestinal microbes which is thought to contribute to increased and persistent inflammation. The purpose of this study is to examine the safety and durability of fecal microbiota transplant (FMT), the transfer of the bacterial community in stool from a healthy donor, in HIV+ individuals on anti-retroviral therapy. The study will also measure the effects of FMT on immune activation and inflammatory biomarkers in anti-retroviral treated HIV+ individuals.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Despite antiretroviral therapy (ART), chronic immune activation persists and is a major driver of HIV disease progression and mortality among HIV-infected individuals. Importantly, persistent inflammation is strongly associated with increased cardiovascular events, accelerated liver disease, impaired immunologic recovery (e.g. low CD4 count, low CD4 to CD8 ratio), and mortality. Therefore, addressing persistent inflammation remains a major goal to restoring health in HIV-infected individuals.

Novel therapeutic strategies to decrease immune activation in treated HIV infection are needed. Marked disruption of the gut microbial composition, or dysbiosis, is characteristic of HIV-infected individuals and persists despite long-term ART. Recent studies demonstrate that the relative degree of gut microbiome disruption positively correlates with inflammatory markers (IL-6, kynurenine to tryptophan ratio). Microbial dysbiosis and its inflammatory consequences may be an attractive target for interventions to decrease immune activation in HIV+ individuals.

Fecal microbiome transplantation (FMT) has proven durable and successful as a therapeutic strategy against gut dysbiosis, such as in the treatment of recurrent Clostridium difficile infection, by restructuring the composition of the gut microbiome to resemble that of the healthy donor. FMT has an established record of safety with limited adverse effects, even in the context of immunocompromised and HIV-infected subjects. Donor selection and screening will be conducted by OpenBiome.

The objective of this phase I clinical trial is to establish the safety and durability of FMT in HIV+ individuals. The microbiome of recipients will be analyzed up to 8 weeks post FMT for evidence of engraftment from the donor microbiome. We will further examine the effect of FMT on markers of immune activation and inflammation in ART treated HIV-infected individuals.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • California
      • San Francisco, California, United States, 94110
        • University of California, San Francisco-San Francisco General Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 75 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. HIV infected men and women 18-75 years of age.
  2. On continuous anti-retroviral therapy for at least one year.
  3. Undetectable viral load for at least one year.
  4. Written informed consent obtained from the subject and ability of the subject to comply with the requirements of the study.

Exclusion Criteria:

  1. CD4 T cell count less than 200 cells/mL.
  2. Recent antibiotic use in the last 3 months.
  3. Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
  4. Presence of a condition or abnormality that in the opinion of the Investigator would compromise the safety of the patient or the quality of the data.
  5. Active GI symptoms: inflammatory bowel disease, abdominal pain, hematochezia, or other symptoms requiring medical evaluation and intervention.
  6. Recent hospitalization or acute medical condition within preceding three months.
  7. Severe comorbidities: cirrhosis, coagulopathy, heart failure, renal failure, and respiratory failure.
  8. Testing positive for any of the stool screening test: Clostridium difficile toxin by PCR, routine bacterial culture for enteric pathogens (E coli, Salmonella, Shigella, Yersinia, Campylobacter), culture for Vibrio, fecal Giardia antigen, fecal Cryptosporidium antigen, acid-fast stain for Cyclospora and Isospora, ova and parasites, stool for Rotavirus via EIA.
  9. History of anaphylaxis.
  10. Major immunosuppressive medications (e.g., calcineurin inhibitors, exogenous glucocorticoids, biological agents, etc.) or systemic antineoplastic agents.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Fecal microbiota transplant (FMT)
Donor fecal suspension will be delivered during colonoscopy to HIV+ individuals.
Drug: Fecal Microbiota
300 mL of fecal suspension from a healthy donor will be delivered during colonoscopy
Other Names:
  • stool transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Safety of FMT in HIV-infected individuals on suppressive ART.
Time Frame: 0-24 weeks post-FMT
Determine the proportion of individuals with AE/SAE. Record AE/SAE during FMT and post-FMT and determine if related to study procedure and graded for severity. Study stoppage criteria includes any serious AE that is at least possibly related to study treatment or any serious infection (e.g., bacteremia) in a sterile body site with an organism potentially acquired from the FMT product.
0-24 weeks post-FMT
Engraftment of donor microbiome in HIV-infected individuals on suppressive ART.
Time Frame: 8 weeks post-FMT
The weighted Canberra distance, which calculates community similarity based on shared OTU membership irrespective of phylogenetic relatedness, and weighted UniFrac which considers phylogenetic similarity of microbial communities, will both be applied to compare the microbiome of FMT recipients over time to those of the donor infusion sample.
8 weeks post-FMT

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Plasma will be analyzed for changes in levels of markers of inflammation (e.g. IL-6, sCD14, kynurenine to tryptophan ratio) and CD4 and CD8 T cell activation
Time Frame: 8 weeks post-FMT
pre-FMT and 8 weeks post-FMT.
8 weeks post-FMT

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of California, San Francisco

Collaborators

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
American College of Gastroenterology

Investigators

  • Principal Investigator: Ma Somsouk, MD, University of California, San Francisco

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2014

Primary Completion (Actual)

March 1, 2017

Study Completion (Actual)

March 1, 2017

Study Registration Dates

First Submitted

October 1, 2014

First Submitted That Met QC Criteria

October 2, 2014

First Posted (Estimate)

October 3, 2014

Study Record Updates

Last Update Posted (Actual)

May 4, 2017

Last Update Submitted That Met QC Criteria

May 2, 2017

Last Verified

May 1, 2017

More Information

Terms related to this study

Keywords

Other Study ID Numbers

  • 13-12675

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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