Using fecal microbiota transplantation to reduce inflammation in people living with HIV

Fecal Microbiota Transplantation to Reduce Immune Activation in ART-treated People Living With HIV With Low CD4/CD8 Ratio: The Gutsy Study

This study is testing if fecal microbiota transplantation can help reduce inflammation in people living with HIV who are already on treatment.

Quick facts

• Phase: PHASE2
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: McGill University Health Centre/Research Institute of the McGill University Health Centre (other)
• Locations: 1 site (Montréal, Quebec)
• Trial ID: NCT06022406 on ClinicalTrials.gov

What this trial studies

This pilot study aims to evaluate the effectiveness of fecal microbiota transplantation (FMT) in reducing gut and systemic inflammation in individuals with HIV who are on antiretroviral therapy and have a low CD4/CD8 ratio. Participants will be randomly assigned to receive either FMT capsules or placebo capsules over a period of three weeks, with assessments of gut permeability and inflammation conducted before and after the intervention. The study will also include an optional substudy involving colonoscopy to further investigate gut health and HIV reservoir size. By comparing the outcomes between the FMT and placebo groups, researchers hope to determine the potential benefits of FMT in this population.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with documented HIV-1 infection, stable on antiretroviral therapy for at least three years, and exhibiting a low CD4/CD8 ratio.

Not a fit: Patients with undetectable viral loads above 50 copies/ml or those not on stable ART for the required duration may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce inflammation and improve gut health in people living with HIV, potentially lowering the risk of non-AIDS-related health issues.

How similar studies have performed: While FMT has shown promise in treating other conditions, this specific application in HIV is novel and has not been extensively tested in prior studies.

Eligibility criteria

Inclusion Criteria:

1. Male or female adults ≥18 years of age.
2. Documented HIV-1 infection by Western Blot, Enzyme Immuno Assay (EIA) or viral load assay.
3. On ART for at least 3 years, and stable ART regimen (same prescription) for at least 3 months.
4. 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.
5. 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.
6. Able to communicate adequately in either French or English.
7. Able and willing to provide written informed consent prior to screening.
8. Women of childbearing potential must have a negative serum pregnancy test at Screening
9. 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):

   1. Complete abstinence from penile-vaginal intercourse from the screening period until 2 weeks after study completion.
   2. Double barrier method (acceptable barrier methods include diaphragm, coil, contraceptive foam, sponge with spermicide, or condom).
   3. Oral, injectable or implant contraceptives plus one barrier method.
   4. 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.
   5. Male partner sterilization confirmed prior to the female participant's entry into the study; this male is the sole partner for that participant.
   6. Approved hormonal contraception, started at least 30 days before screening, preferably with one barrier method.
   7. Another method approved by the Investigator with published data showing that the expected failure rate is \<1% per year preferably with one barrier method.
10. Women of non-child-bearing potential as defined as either post-menopausal (12 months of spontaneous amenorrhea and ≥ 45 years of age) or physically incapable of becoming pregnant with documented tubal ligation, hysterectomy or bilateral oophorectomy.
11. Sexually active men with a female partner of childbearing potential must agree to one of the following methods of birth control (See Section 7.1):

    1. The use of at least one barrier method of contraception (e.g. condom) with a female partner using a second approved method of contraception (IUD, hormonal contraceptive pill, diaphragm, spermicide, etc.) during the study and until two weeks after study completion.
    2. Have had a successful vasectomy.
    3. Be confirmed sterile. Any contraception method must be used consistently, in accordance with this study protocol, and for the duration of the study until two weeks after study completion.

Exclusion Criteria:

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

Where this trial is running

Montréal, Quebec

• Chronic Viral Illness Service — Montréal, Quebec, Canada (RECRUITING)

Study contacts

• Study coordinator: Carolina A Berini, Dr.

Conditions: HIV-1-infection, HIV, Low CD4/CD8 ratio, Dysbiosis