Fecal Microbiota Transplantation in HIV (FMT-HIV)
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|ClinicalTrials.gov Identifier: NCT02256592|
Recruitment Status : Completed
First Posted : October 3, 2014
Last Update Posted : May 4, 2017
|Condition or disease||Intervention/treatment||Phase|
|HIV||Drug: Fecal Microbiota||Phase 1|
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 (Clinical Trial)|
|Actual Enrollment :||18 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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
- 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.
- 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.
- 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02256592
|United States, California|
|University of California, San Francisco-San Francisco General Hospital|
|San Francisco, California, United States, 94110|
|Principal Investigator:||Ma Somsouk, MD||University of California, San Francisco|