Fecal Microbiota Transplantation for HIV

(Gutsy Trial)

Overseen By Stephane Isnard, Dr.

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Jean-Pierre Routy

Must be taking: ART

Must not be taking: Immune-modulatory, Antibiotics, Morphine

Disqualifiers: AIDS, Hepatitis B/C, Diabetes, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 4

Duration: 6 weeks

20 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a stable ART regimen for at least 3 months. If you are using immune-modulatory agents, prophylactic antibiotics, or morphine, you cannot participate in the trial.

What data supports the effectiveness of the treatment Fecal Microbiota Transplantation (FMT) for HIV?

FMT is effective for treating recurrent Clostridium difficile infections and shows promise for other conditions like inflammatory bowel disease, suggesting potential benefits for HIV-related issues. ^{1 2 3 4 5}

Is fecal microbiota transplantation (FMT) safe for humans?

Fecal microbiota transplantation (FMT) is generally considered safe and well-tolerated, especially for treating recurrent Clostridioides difficile infections. Most short-term risks are mild, but there have been serious adverse events linked to FMT products from stool banks that did not screen for multi-drug resistant organisms. Long-term side effects are not well-established, and safety concerns are higher in people with weakened immune systems. ^{3 4 6 7 8}

How is fecal microbiota transplantation different from other treatments for HIV?

Fecal microbiota transplantation (FMT) is unique because it involves transferring stool from a healthy donor to a patient to restore the natural balance of bacteria in the gut, which is different from traditional HIV treatments that typically involve antiviral drugs. While FMT is well-studied for recurrent Clostridium difficile infections, its use in HIV is still being researched, making it a novel approach. ^{4 5 9 10 11}

Research Team

Carolina Berini, Dr.

Principal Investigator

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

Eligibility Criteria

This trial is for adults over 18 with HIV who've been on ART for at least 3 years, have an undetectable viral load, and a low CD4/CD8 ratio indicating inflammation risks. They must understand French or English and agree to specific contraception methods if of childbearing potential.

Inclusion Criteria

CD4 count between greater than 200 cells/µL and a CD4/CD8 ratio below 1

Women of childbearing potential must agree to use approved methods of birth control while in the study and until 2 weeks after completion of the study

I can communicate well in either French or English.

Exclusion Criteria

I have not had AIDS-related health issues or serious infections in the last 3 months.

I am pregnant, planning to become pregnant, or am breastfeeding.

I have not been in a clinical trial or received experimental therapy in the last 6 months.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive FMT or placebo capsules twice at 3-week intervals to ensure engraftment

6 weeks

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including optional colonoscopy to assess gut inflammation and HIV reservoir size

12 weeks

2 visits (in-person)

Treatment Details

Interventions

• Fecal Microbiota Transplantation (FMT)

Trial Overview The study tests whether FMT capsules can reduce gut and systemic inflammation in people living with HIV compared to placebo capsules. It involves two groups: one receiving the FMT and the other a placebo, with treatments given twice over three weeks.

Participant Groups

Group I: FMT capsules Experimental Treatment 1 Intervention

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).

Group II: Placebo capsules Placebo Group 1 Intervention

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.

Fecal Microbiota Transplantation (FMT) is already approved in European Union, United States for the following indications:

Approved in European Union as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Approved in United States as Fecal Microbiota Transplantation for:

• Recurrent Clostridium difficile infection

Who Is Running the Clinical Trial?

Jean-Pierre Routy

Lead Sponsor

Trials

3

Recruited

130+

St. Joseph's Health Care London

Collaborator

Trials

28

Recruited

2,500+

Findings from Research

Faecal microbiota transplantation (FMT) has shown significant benefits in treating ulcerative colitis, with four randomized controlled trials indicating its effectiveness compared to placebo.

Research is ongoing to optimize donor and patient selection for FMT, and complementary strategies like pre-antibiotics are being explored to enhance treatment efficacy, although data for Crohn's disease and pouchitis are still limited.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease. Haifer, C., Leong, RW., Paramsothy, S.[2021]

Fecal microbiota transplantation (FMT) using targeted colonic release capsules (FMTcr) showed a slightly higher clinical cure rate for recurrent Clostridium difficile infection (rCDI) at 80.6% compared to 75% for gastric release capsules (FMTgr), although the difference was not statistically significant.

Both FMT formulations were found to be safe with no serious adverse events, but FMTcr was more effective in increasing gut microbial diversity, suggesting better microbial engraftment patterns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose. Allegretti, JR., Fischer, M., Sagi, SV., et al.[2020]

Fecal microbiota transplantation (FMT) was successfully performed in two immunocompromised children with refractory diarrhea, leading to symptom remission without any infectious complications.

The procedure resulted in the reconstruction of a diverse microbiota, indicating that FMT is a safe and effective treatment option for managing diarrhea in immunocompromised patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report. Zhong, S., Zeng, J., Deng, Z., et al.[2020]

Fecal microbiota transplantation (FMT) has a total adverse event (AE) incidence rate of 28.5%, with abdominal discomfort being the most common AE reported in 19 studies, highlighting the need for careful monitoring during the procedure.

Serious adverse events (SAEs) occurred in 9.2% of patients, with a notable incidence of death (3.5%) and infections (2.5%), indicating that while FMT can be beneficial, it carries significant risks that require further investigation through high-quality randomized controlled trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. Wang, S., Xu, M., Wang, W., et al.[2023]

Fecal microbiota transplantation (FMT) is a cost-effective treatment for recurrent Clostridium difficile infection (rCDI), with all economic evaluations showing it to be more cost-effective than other standard treatments at a threshold of ≤$50,000 per quality-adjusted life year (QALY).

The systematic review included 9 high-quality economic evaluations, primarily focusing on rCDI and inflammatory bowel disease (IBD), indicating that while FMT is effective for rCDI, further studies are needed to explore its economic impact for other conditions like IBD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A systematic review of economic evaluation in fecal microbiota transplantation. Stalder, T., Kapel, N., Diaz, S., et al.[2021]

Fecal microbiota transplantation (FMT) is a generally safe and well-tolerated procedure for treating recurrent Clostridioides difficile infections, even in high-risk patients, with most short-term risks being mild and related to delivery methods.

Recent concerns have emerged regarding serious adverse events linked to FMT products from stool banks that do not screen for multi-drug resistant organisms, highlighting the need for improved safety protocols.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? Park, SY., Seo, GS.[2021]

Fecal microbiota transplantation (FMT) is highly effective for treating Clostridium difficile infection (CDI), with a 90% resolution of diarrhea reported in 867 patients across 33 studies, and a 94% resolution after repeated FMT in a randomized controlled trial with 16 participants.

FMT shows promise in treating ulcerative colitis, with remission rates varying from 0% to 68% in 106 patients, while its efficacy in Crohn's disease, chronic constipation, pouchitis, and irritable bowel syndrome remains inconclusive due to limited data.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. Rossen, NG., MacDonald, JK., de Vries, EM., et al.[2022]

In a study of 6 pediatric solid organ transplant (SOT) recipients who received fecal microbiota transplant (FMT) for recurrent Clostridioides difficile infection (CDI), the treatment showed an 83.3% success rate in preventing CDI recurrence within 2 months.

While FMT was generally safe, one serious adverse event occurred (cecal perforation) in a kidney transplant recipient, highlighting a potential increased risk for SOT patients, though no adverse events related to immunosuppression or transplant status were observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients. Rodig, NM., Weatherly, M., Kaplan, AL., et al.[2023]

A survey of 107 Korean physicians revealed that 61.7% had experience with fecal microbiota transplantation (FMT), and 80.4% were willing to use it for treating recurrent Clostridioides difficile infection (CDI).

While two-thirds of physicians would consider FMT for patients with recurrent CDI after three or more recurrences, concerns about regulations and low efficacy for non-CDI diseases were significant barriers to broader use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recognition and attitudes of Korean physicians toward fecal microbiota transplantation: a survey study. Gweon, TG., Lee, YJ., Yim, SK., et al.[2023]

Fecal microbiota transplantation (FMT) is primarily effective for treating recurrent Clostridium difficile infections by restoring a healthy microbiome in the colon.

Currently, there is not enough evidence to support the use of FMT for other gastrointestinal or nongastrointestinal diseases, although research is ongoing in these areas.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation. Vindigni, SM., Surawicz, CM.[2020]

Fecal microbiota transplantation (FMT) is an effective method for restoring healthy gut flora in patients suffering from Clostridium difficile infection (CDI).

There is a need for further research to understand how FMT can be safely and effectively used in cancer patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in patients with cancer undergoing treatment. Blackburn, LM., Bales, A., Caldwell, M., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

The role of faecal microbiota transplantation in the treatment of inflammatory bowel disease. [2021]

2. United States pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation Capsules with Targeted Colonic Versus Gastric Delivery in Recurrent Clostridium difficile Infection: A Comparative Cohort Analysis of High and Lose Dose. [2020]

3. England pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation for refractory diarrhea in immunocompromised diseases: a pediatric case report. [2020]

4. United States pubmed.ncbi.nlm.nih.gov

Systematic Review: Adverse Events of Fecal Microbiota Transplantation. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

A systematic review of economic evaluation in fecal microbiota transplantation. [2021]

6. Korea (South) pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation: Is It Safe? [2021]

7. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation as novel therapy in gastroenterology: A systematic review. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplant in Pediatric Solid Organ Transplant Recipients. [2023]

9. Korea (South) pubmed.ncbi.nlm.nih.gov

Recognition and attitudes of Korean physicians toward fecal microbiota transplantation: a survey study. [2023]

10. United States pubmed.ncbi.nlm.nih.gov

Fecal Microbiota Transplantation. [2020]

11. United States pubmed.ncbi.nlm.nih.gov

Fecal microbiota transplantation in patients with cancer undergoing treatment. [2020]