Fecal Microbiota Transplantation in HIV

NCT02256592 | Completed Phase 1

• 1 other identifier: 13-12675
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

HIV

Keywords

inflammation; microbiome; immune activation; fecal microbiota transplantation; dysbiosis

Outcome Measures

Primary Outcomes (2)

• Safety of FMT in HIV-infected individuals on suppressive ART.

  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.

  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 Outcomes (1)

• 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

  8 weeks post-FMT

Study Arms (1)

Fecal microbiota transplant (FMT)

EXPERIMENTAL

Donor fecal suspension will be delivered during colonoscopy to HIV+ individuals.

Drug: Fecal Microbiota

Interventions

Fecal Microbiota DRUG

300 mL of fecal suspension from a healthy donor will be delivered during colonoscopy

Also known as: stool transplant

Fecal microbiota transplant (FMT)

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• CD4 T cell count less than 200 cells/mL.
• Recent antibiotic use in the last 3 months.
• Pregnant, breastfeeding, or unwilling to practice birth control during participation in the study.
• 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.
• Active GI symptoms: inflammatory bowel disease, abdominal pain, hematochezia, or other symptoms requiring medical evaluation and intervention.
• Recent hospitalization or acute medical condition within preceding three months.
• Severe comorbidities: cirrhosis, coagulopathy, heart failure, renal failure, and respiratory failure.
• 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.
• History of anaphylaxis.
• Major immunosuppressive medications (e.g., calcineurin inhibitors, exogenous glucocorticoids, biological agents, etc.) or systemic antineoplastic agents.

Sponsors & Collaborators

• University of California, San Francisco: lead
• American College of Gastroenterology: collaborator
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

University of California, San Francisco-San Francisco General Hospital

San Francisco, California, 94110, United States

Location

Related Publications (2)

• Duprez DA, Neuhaus J, Kuller LH, Tracy R, Belloso W, De Wit S, Drummond F, Lane HC, Ledergerber B, Lundgren J, Nixon D, Paton NI, Prineas RJ, Neaton JD; INSIGHT SMART Study Group. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. PLoS One. 2012;7(9):e44454. doi: 10.1371/journal.pone.0044454. Epub 2012 Sep 10.

  PMID: 22970224 BACKGROUND

• Vujkovic-Cvijin I, Dunham RM, Iwai S, Maher MC, Albright RG, Broadhurst MJ, Hernandez RD, Lederman MM, Huang Y, Somsouk M, Deeks SG, Hunt PW, Lynch SV, McCune JM. Dysbiosis of the gut microbiota is associated with HIV disease progression and tryptophan catabolism. Sci Transl Med. 2013 Jul 10;5(193):193ra91. doi: 10.1126/scitranslmed.3006438.

  PMID: 23843452 BACKGROUND

MeSH Terms

Conditions

Inflammation; Dysbiosis

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Ma Somsouk, MD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: October 1, 2014
• First Posted: October 3, 2014
• Study Start: October 1, 2014
• Primary Completion: March 1, 2017
• Study Completion: March 1, 2017
• Last Updated: May 4, 2017

Record last verified: 2017-05

Locations

US (1)