CTNPT 038: The Gutsy Study

About The Study

The purpose of this study is to see if taking fecal microbiota transplantation (FMT) in capsules in addition to antiretroviral therapy (ART) can reduce inflammation and immune activation. This study will also examine what effects FMT capsules has on the types of bacteria in the gut and explore if FMT capsules has any effect on the HIV reservoir (HIV virus hidden in cells) in the blood and the gut.

Participants at the Montreal site that take part in the study will have the option to take part in a sub-study that will involve colon biopsies. The purpose of the optional sub-study is to assess changes in gut mucosa. The mucosa is the lining of the gut which helps stop pathogens from entering the body.

Background

When used consistently, ART decreases HIV in the blood leading to improved health in people living with HIV. However, people living with HIV remain at higher risk for developing certain inflammatory-health conditions including diabetes, fatty liver, cardiovascular disease, brain-related diseases and cancer.

HIV keeps immune cells in an active or inflammatory state, partly due to the damage HIV does to the gut. The lining of the gut acts as a barrier and prevents undesirable gut contents (e.g. bad bacteria) from traveling through the gut lining into the blood. These gut compounds entering the bloodstream trigger inflammation and over time can increase the risk of inflammatory-related health conditions. ART medication helps repair some of the damage caused by HIV; however, ART does not reduce the number of bacterial compounds crossing the gut lining to levels seen in healthy HIV-negative people. There is a need to find therapies to decrease this chronic inflammation in people living with HIV.

The gut contains tens of trillions of microorganisms, including at least 1000 different types of bacteria. Many bacteria are “good” and act as a barrier to prevent gut damage. When the types of bacteria in the gut is out of balance (there are less “good” bacteria) this can have a negative effect on gut health, which can cause leaking and lead to inflammation. This has been shown to occur with HIV infection. Changing the types of bacteria in the gut so that there are more bacteria that are beneficial has been shown to partially reduce inflammation in people with inflammatory diseases.

One way to improve the composition of the gut bacteria is by fecal microbiota transplantation (FMT), which aims at replacing gut microbes with microbes from a selected healthy donor. This study aims to explore the possibility that FMT can improve gut health and decrease inflammation in people living with HIV.

Study Approach

Study researchers will recruit 20 adults that have taken ART for three years or more. Participants will be randomized 1:1 to receive FMT or placebo capsules (10 participants in each group) to be taken orally. The study will take place over approximately 3-5 months and over the course of the study participants will visit the clinic 6 times to take the FMT or placebo capsules and to give blood and stool.

Participants at the Montreal site that agree to take part in the sub-study will have a colonoscopy at the beginning and the end of the study so that researchers can assess changes in the gut mucosa (lining of the gut). Blood samples will be used to measure the HIV reservoir, gut damage and inflammation markers, and microbial translocation or inflammation. Stool samples will be used for microbiota analysis.