Ignite Creation Date:
2025-12-26 @ 10:59 AM
Ignite Modification Date:
2025-12-26 @ 10:59 AM
Study NCT ID:
NCT06022406
Status:
COMPLETED
Last Update Posted:
2025-09-03
First Post:
2023-08-04
Is NOT Gene Therapy:
False
Has Adverse Events:
False
Brief Title:
Fecal Microbiota Translantation (FMT) to Reduce Inflammation in PLWH: The Gutsy Pilot Study
Sponsor:
Jean-Pierre Routy
Organization:
Study Overview
Official Title:
Fecal Microbiota Transplantation to Reduce Immune Activation in ART-treated People Living With HIV With Low CD4/CD8 Ratio: The Gutsy Study
Status:
COMPLETED
Status Verified Date:
2025-08
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
Gutsy
Brief Summary:
The goal of this randomized, single blind, two-armed pilot study is to assess the efficacy of FMT in reducing gut mucosal and systemic inflammation in ART-treated people living with HIV with low CD4/CD8 ratio. The main questions it aims to answer are: •Is there a change in the gut permeability among participants taking FMT compared to placebo? • Has inflammation been reduced by the use of FMT? Ten participants will be randomized to receive FMT in capsules, and another 10 participants will receive placebo capsules containing microcrystalline cellulose. Capsules will be given twice (30 to 40 capsules at each treatment) at 3 weeks interval, to ensure engraftment. In an optional substudy, participants will be asked to undergo colonoscopy before and 3 months after FMT to assess gut inflammation and HIV reservoir size in colon biopsies. Researchers will compare the FMT arm and the Placebo arm to see if there are differences in gut permeability and inflammation.
Detailed Description:
Background: HIV infection is characterized by a rapid mucosal CD4 T-cell depletion and early epithelial gut damage. People living with HIV (PLWH) have an abnormal gastrointestinal landscape characterized by villous atrophy, crypt hyperplasia, loosened tight junctions, gastrointestinal inflammation and increased intestinal permeability. Despite long-term antiretroviral therapy (ART), gut mucosa damage remains in PLWH. Increased gut permeability allows the translocation of microbial products into the mucosa and the blood. This process, called microbial translocation, has been associated with increased inflammation and the development of non-AIDS events such as cardiovascular diseases, neurocognitive dysfunction and some cancers in ART-treated PLWH.
Gut damage and persistent inflammation were associated with the modification of the gut microbiota, called dysbiosis, which persists in PLWH under ART. Hence, therapies targeting the gut mucosa are a must.
Minor changes were obtained with Lactobacillus-based probiotics aiming at balancing microbiota composition in PLWH. A promising intervention is the use of fecal microbial transplantation (FMT), which consist of delivering stool microbiota from a donor by upper-endoscopy in the stomach or colonoscopy. More recently, oral delivery of encapsulated stool preparation was shown to lead to a more stable engraftment of the donor's microbiota. FMT was primarily used to eliminate Clostridium difficile infection. FMT is not commonly used in PLWH, but macaque models gave promising results with reduced gut inflammation post FMT in SIV-infected monkeys.
Objectives: To assess, before and after FMT, in the FMT compared to place group:
* Plasma levels of gut damage markers (Intestinal Fatty acid Binding protein) and the new marker of gut permeability Regenerating Islet Derived protein 3 α (REG3α).
* Inflammatory cytokines and T and Myeloid cell activation in blood and colon biopsies
* Changes in stools microbiota composition
* Changes in mucosal and blood HIV reservoir size
* Safety of FMT
Methods: To perform a randomized, single blind, two-armed pilot study in HIV-infected ART treated participant with a low CD4/CD8 ratio which are at higher risk of inflammation and dysbiosis. Ten participants will be randomized to receive FMT in capsules, and another 10 will receive placebo capsules containing microcrystalline cellulose. Capsules will be given twice (30 to 40 capsules at each treatment) at 3 weeks interval, to ensure engraftment. Safety will be assessed. In an optional substudy, participants will be asked to undergo colonoscopy before and 3 months after FMT to assess gut inflammation and HIV reservoir size in colon biopsies.
Anticipated results: We expect that FMT will reduce gut mucosal and systemic inflammation. This study should provide sufficient results for calculation of power in a larger scale trial in PLWH.
Gut damage and persistent inflammation were associated with the modification of the gut microbiota, called dysbiosis, which persists in PLWH under ART. Hence, therapies targeting the gut mucosa are a must.
Minor changes were obtained with Lactobacillus-based probiotics aiming at balancing microbiota composition in PLWH. A promising intervention is the use of fecal microbial transplantation (FMT), which consist of delivering stool microbiota from a donor by upper-endoscopy in the stomach or colonoscopy. More recently, oral delivery of encapsulated stool preparation was shown to lead to a more stable engraftment of the donor's microbiota. FMT was primarily used to eliminate Clostridium difficile infection. FMT is not commonly used in PLWH, but macaque models gave promising results with reduced gut inflammation post FMT in SIV-infected monkeys.
Objectives: To assess, before and after FMT, in the FMT compared to place group:
* Plasma levels of gut damage markers (Intestinal Fatty acid Binding protein) and the new marker of gut permeability Regenerating Islet Derived protein 3 α (REG3α).
* Inflammatory cytokines and T and Myeloid cell activation in blood and colon biopsies
* Changes in stools microbiota composition
* Changes in mucosal and blood HIV reservoir size
* Safety of FMT
Methods: To perform a randomized, single blind, two-armed pilot study in HIV-infected ART treated participant with a low CD4/CD8 ratio which are at higher risk of inflammation and dysbiosis. Ten participants will be randomized to receive FMT in capsules, and another 10 will receive placebo capsules containing microcrystalline cellulose. Capsules will be given twice (30 to 40 capsules at each treatment) at 3 weeks interval, to ensure engraftment. Safety will be assessed. In an optional substudy, participants will be asked to undergo colonoscopy before and 3 months after FMT to assess gut inflammation and HIV reservoir size in colon biopsies.
Anticipated results: We expect that FMT will reduce gut mucosal and systemic inflammation. This study should provide sufficient results for calculation of power in a larger scale trial in PLWH.
Study Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: