Fecal Microbiota Translantation (FMT) to Reduce Inflammation in PLWH: The Gutsy Pilot Study

NCT06022406 | Completed Phase 2 DMC

• 1 other identifier: 2023-9477
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

HIV-1-infection

Keywords

HIV; Low CD4/CD8 ratio; Dysbiosis

Outcome Measures

Primary Outcomes (1)

• REG3α levels

  Changes in plasma REG3α levels will be measured as markers of gut permeability

  12 weeks

Secondary Outcomes (17)

• Safety of FMT

  12 weeks

• Tolerability of FMT

  12 weeks

• Changes in plasma levels of gut damage markers

  12 weeks

• Changes in plasma levels of gut damage markers

  12 weeks

• Changes in Plasma levels of pro-inflammatory markers

  12 weeks

Study Arms (2)

FMT capsules

EXPERIMENTAL

10 participants taking FMT. The study product consists of fecal microbiota capsules prepared by Dr. Silverman's team in London, Ontario, Canada. Dr. Silverman has received approval from Health Canada to evaluate FMT in patients with metastatic malignant melanoma or with fatty liver within a clinical trial setting (CTA control nos. 235387and 195078 respectively). Approximately 30 to 40 capsules will be prepared from 80-100g of healthy human feces from a single healthy donor and administered as a single dose. Capsules will be prepared by a modified method as described by Kao et al, 201747,48 (see Investigator brochure).

Biological: FMT capsules

Placebo capsules

PLACEBO COMPARATOR

10 participants taking Placebo. Placebo capsules contain microcrystalline cellulose, for equivalence in weight and color that will be encapsulated in gelatin capsules. Each capsule will be filled with approximatively 5.5g of microcrystalline cellulose, and encapsulated in size 0 and size 00 capsules.

Biological: Placebo capsules

Interventions

FMT capsules BIOLOGICAL

Formulation: 80-100g of healthy donor stool processed, frozen and encapsulated in gelatin capsules (modified Kao et al, 2017).

FMT capsules

Placebo capsules BIOLOGICAL

Formulation: microcrystalline cellulose, for equivalence in weight and color, will be encapsulated in gelatin capsules. Each capsule will be filled with approximatively 5.5g of microcrystalline cellulose, and encapsulated in size 0 and size 00 capsules.

Placebo capsules

Eligibility Criteria

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

You may qualify if:

• Male or female adults ≥18 years of age.
• Documented HIV-1 infection by Western Blot, Enzyme Immuno Assay (EIA) or viral load assay.
• On ART for at least 3 years, and stable ART regimen (same prescription) for at least 3 months.
• Undetectable viral load \< 50 copies/ml for the past 3 years. Viral blips below 200 copies/ml, are allowed if preceded and followed by a HIV viremia below 50 copies/ml.
• CD4 count between greater than 200 cells/µL and a CD4/CD8 ratio below 1 to select people with higher risks of inflammatory non-AIDS comorbidities and dysbiosis.
• Able to communicate adequately in either French or English.
• Able and willing to provide written informed consent prior to screening.
• Women of childbearing potential must have a negative serum pregnancy test at Screening
• Women of childbearing potential must agree to use one of the following approved methods of birth control while in the study and until 2 weeks after completion of the study (See Section 7.1):
• Complete abstinence from penile-vaginal intercourse from the screening period until 2 weeks after study completion.
• Double barrier method (acceptable barrier methods include diaphragm, coil, contraceptive foam, sponge with spermicide, or condom).
• Oral, injectable or implant contraceptives plus one barrier method.
• Any intrauterine device (IUD) with published data showing that the expected failure rate is \<1% per year (not all IUDs meet this criterion) plus one barrier method.
• Male partner sterilization confirmed prior to the female participant's entry into the study; this male is the sole partner for that participant.
• Approved hormonal contraception, started at least 30 days before screening, preferably with one barrier method.

You may not qualify if:

• Known allergy/hypersensitivity Polyethylene glycol.
• Current AIDS-related event or serious health condition including systemic infections in the last 3 months.
• Severe systemic diseases (e.g. uncontrolled hypertension, chronic renal failure), or active uncontrolled infections.
• Co-infection with active Hepatitis B or C Virus.
• Current use or have used in the past 3 months: immune-modulatory agents, prophylactic antibiotics45/antibiotics, or Morphine as these drugs modulate gut microbiota.
• Diagnosis of diabetes mellitus (HbA1c≥6.5%) as defined by the Canadian Clinical Practice Guidelines for the Prevention and Management of Diabetes46.
• Recent changes in dietary habits, intermittent fasting, chronic constipation or laxative use as these can affect gut microbiota.
• Psychiatric or cognitive disturbance or any illness that could preclude compliance with the study.
• Current participation in an experimental therapy study or receipt of experimental therapy within the last 6 months.
• Women who are planning to become or who are pregnant, or breast-feeding.
• A score of higher than 8 on a Full AUDIT questionnaire at the screening visit, suggesting an alcohol abuse problem.

Sponsors & Collaborators

• Jean-Pierre Routy: lead
• St. Joseph's Health Care London: collaborator

Study Sites (1)

Chronic Viral Illness Service

Montreal, Quebec, H4A 3J1, Canada

Location

Related Publications (1)

• Isnard S, Berini CA, Parvathy SN, Feng H, Aiyana O, Royston L, Mabanga T, Lakatos PL, Bessissow T, Klein MB, Lebouche B, Costiniuk CT, Routy B, Silverman MS, Routy JP. Fecal microbiota transplantation to reduce immune activation in ART-treated people with HIV with low CD4/CD8 ratio: protocol for the single-blind, randomized, placebo-controlled Gutsy study (CIHR/CTN PT038). Trials. 2025 Dec 13. doi: 10.1186/s13063-025-09345-0. Online ahead of print.

  PMID: 41390455 DERIVED

MeSH Terms

Conditions

Dysbiosis

Interventions

Fecal Microbiota Transplantation

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Biological Therapy; Therapeutics

Study Officials

• Carolina Berini, Dr.

  McGill University Health Centre/Research Institute of the McGill University Health Centre

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Prior to study commencement, a statistician will develop a randomization list and prepare sequentially numbered sealed envelopes containing the randomization group assignment. In this single blind study, participants will not know which arm they have been assigned to. After screening, upon validation of eligibility, study staff will open the next sequentially numbered envelope to determine which group the study participant has been assigned to. Randomization after screening will allow sufficient time to prepare capsules and have them shipped to the study site before the first treatment visit (Visit 3-Day 0). The randomization group will be recorded on the randomization electronic case report form (eCRF).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Director of the Chronic Viral Illness Service Division of Hematology and Chronic Viral Illness Service Louis Lowenstein Chair in Hematology & Oncology Professor of Medicine, McGill University

Model Details: Single-blind, randomized, placebo-controlled, interventional study

Study Record Dates

• First Submitted: August 4, 2023
• First Posted: September 1, 2023
• Study Start: July 31, 2024
• Primary Completion: August 13, 2025
• Study Completion: August 13, 2025
• Last Updated: September 3, 2025

Record last verified: 2025-08

Locations

CA (1)