Fecal Microbiota Transplantation in HIV (FMT-HIV)

• ClinicalTrials.gov Identifier: NCT02256592
• Recruitment Status: Completed
• First Posted: October 3, 2014
• Last Update Posted: May 4, 2017
• Sponsor: University of California, San Francisco
• Collaborators: American College of Gastroenterology; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Information provided by (Responsible Party): Ma Somsouk, MD, MAS, University of California, San Francisco

Study Description

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.

Condition or disease	Intervention/treatment	Phase
HIV	Drug: Fecal Microbiota	Phase 1

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Reconstitution of the Gut Microbiome to Reduce HIV-Associated Inflammation
• Study Start Date: October 2014
• Actual Primary Completion Date: March 2017
• Actual Study Completion Date: March 2017

Arms and Interventions

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 Name: stool transplant

Outcome Measures

Primary Outcome Measures :

1. 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.
2. 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.

Secondary Outcome Measures :

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 [ Time Frame: 8 weeks post-FMT ]
   pre-FMT and 8 weeks post-FMT.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United States, California

University of California, San Francisco-San Francisco General Hospital

San Francisco, California, United States, 94110

Sponsors and Collaborators

University of California, San Francisco

American College of Gastroenterology

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

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

More Information

Publications:

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.

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. Erratum In: Sci Transl Med. 2017 Nov 8;9(415):

• Responsible Party: Ma Somsouk, MD, MAS, Associate Professor, University of California, San Francisco
• ClinicalTrials.gov Identifier: NCT02256592
• Other Study ID Numbers: 13-12675
• First Posted: October 3, 2014
• Last Update Posted: May 4, 2017
• Last Verified: May 2017

Keywords provided by Ma Somsouk, MD, MAS, University of California, San Francisco:

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