Probiotics for Cardiovascular Disease in HIV+ Individuals

(META HIV CVD Trial)

Overseen By Emily Smith, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Disqualifiers: Not fluent in English

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 months

250 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a probiotic pill can benefit people living with HIV by increasing beneficial gut bacteria and reducing the risk of heart disease and death. Heavy drinking raises these risks by affecting gut bacteria. Participants will receive either a probiotic or a placebo (a pill with no active ingredients) to determine if the probiotic has a positive effect. Prospective participants with HIV should have no issues understanding English. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research on probiotics in people with HIV shows they are generally safe. Studies indicate no major side effects, meaning they don't usually cause serious problems. Data from recent trials suggest that probiotics are well-tolerated in individuals treated for HIV, meaning most can take them without issues. For those considering joining a trial, the probiotic treatment has demonstrated a good safety record so far. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for heart disease in HIV+ individuals?

Most treatments for cardiovascular disease in HIV+ individuals focus on managing blood pressure, cholesterol, or blood sugar levels through medications like statins or antihypertensives. But this new approach uses probiotics, which are beneficial bacteria, to potentially improve heart health by enhancing gut flora balance. Researchers are excited because probiotics might offer a natural way to reduce inflammation and improve metabolic functions, possibly reducing cardiovascular risks without the side effects associated with traditional medications. This could be a game-changer, especially for individuals who struggle with the standard treatments.

What evidence suggests that probiotics might be an effective treatment for cardiovascular disease in HIV+ individuals?

Research has shown that probiotics might help lower the risk of heart disease in people with HIV. In this trial, participants will receive either a probiotic supplement or a placebo. One study found that 45 people with HIV who took a probiotic called Lactobacillus rhamnosus GG for 8 weeks experienced a significant reduction in intestinal inflammation. Less inflammation is linked to a lower risk of heart disease. Another study suggested that probiotics might also reduce heart disease risk for heavy drinkers with HIV. These findings indicate that probiotics may improve gut health and reduce inflammation, potentially lowering the risk of heart disease. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for individuals living with HIV who are fluent in English. It's designed to help those who drink heavily and are at increased risk of heart disease and death due to changes in gut bacteria caused by alcohol.

Inclusion Criteria

HIV infected

Exclusion Criteria

I am not fluent in English.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either a probiotic tailored to alcohol-associated gut dysbiosis or a placebo for 6 months

6 months

Monthly visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurements of inflammation, microbial translocation, and cardiovascular risk

6 months

Bi-monthly visits (in-person)

Extension

Optional continuation of monitoring for long-term effects on cardiovascular and mortality risk

6 months

What Are the Treatments Tested in This Trial?

Interventions

• Placebo
• Probiotic

Trial Overview The study tests if a probiotic pill, which contains healthy gut bacteria, can boost the number of good bacteria in the gut, reduce inflammation, and lower heart disease risk compared to a placebo (a pill with no active ingredients).

How Is the Trial Designed?

Group I: Study Supplement Experimental Treatment 1 Intervention

Probiotic

Group II: Study placebo Placebo Group 1 Intervention

Placebo

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

University of Louisville

Collaborator

Trials

353

Recruited

76,400+

Boston University

Collaborator

Trials

494

Recruited

9,998,000+

Published Research Related to This Trial

In a rat model of systemic inflammatory response syndrome (SIRS), probiotics Lactobacillus acidophilus (LA-5) and Bifidobacterium animalis subsp. lactis (BB-12) significantly reduced myocardial infarction size, suggesting a protective effect against ischemic-reperfusion injury.

The treatment with these probiotics also normalized various inflammatory and immune parameters, indicating their potential to improve cardiovascular health in the context of metabolic and inflammatory disorders.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Probiotic Strains on Myocardial Infarction Size, Biochemical and Immunological Parameters in Rats with Systemic Inflammatory Response Syndrome and Polymorbidity. Borshchev, YY., Sonin, DL., Burovenko, IY., et al.[2023]

In a study of 45 HIV-infected individuals, taking the probiotic Lactobacillus rhamnosus GG (LGG) for 8 weeks significantly reduced intestinal inflammation, as shown by PET/MRI scans.

LGG supplementation also led to a decrease in harmful gut bacteria, specifically Enterobacteriaceae, suggesting a potential mechanism for its anti-inflammatory effects in the gut.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Lactobacillus rhamnosus GG Supplementation on Intestinal Inflammation Assessed by PET/MRI Scans and Gut Microbiota Composition in HIV-Infected Individuals. Arnbjerg, CJ., Vestad, B., Hov, JR., et al.[2022]

In a phase 2b trial involving 29 HIV-positive individuals with low CD4+ T-cell counts, probiotic supplementation (De Simone Formulation Probiotic) did not significantly reduce immune activation markers compared to placebo after 48 weeks.

Interestingly, while CD4+ T-cell activation decreased in the placebo group, it increased in the probiotic group, suggesting that the probiotic may not be beneficial and could potentially lead to increased immune activation in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Randomized, Blinded, Placebo-Controlled Trial of De Simone Formulation Probiotic During HIV-Associated Suboptimal CD4+ T Cell Recovery. Rousseau, RK., Walmsley, SL., Lee, T., et al.[2022]

Probiotic administration may help protect the gut and delay the progression of HIV-1 to AIDS by stabilizing CD4+ T cell numbers and reducing inflammation, as shown in various studies over the past five years.

Supplementation with specific probiotics, like Bifidobacterium lactis, has been linked to improved growth in infants with congenital HIV-1 infection and has shown promise in enhancing immune responses and reducing chronic immune activation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of probiotic bacteria on microbial host defense, growth, and immune function in human immunodeficiency virus type-1 infection. Cunningham-Rundles, S., Ahrné, S., Johann-Liang, R., et al.[2021]

Probiotic supplementation significantly improved CD4+ T-cell counts in HIV-infected children, with a mean increase of 123.92 cells/mm³, indicating a potential benefit in managing HIV-related immune issues.

No adverse effects were reported from probiotic use, suggesting that they are a safe adjunct therapy alongside standard antiretroviral treatment (ART) for pediatric patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of Probiotics on the Frequency of CD4+ T-Cells in HIV-Infected Children and Adolescents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Sachdeva, M., Sra, HK., Agarwal, A., et al.[2022]

A systematic review and meta-analysis of 16 randomized controlled trials involving probiotics, prebiotics, and synbiotics found no significant improvement in CD4+ T-cell counts in HIV-infected patients compared to placebo, indicating limited efficacy of these supplements.

Subgroup analysis revealed a significant increase in CD4 counts in studies with a high risk of bias, suggesting that the overall evidence is insufficient and that more rigorous research is needed to clarify the effects of these interventions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Probiotics, Prebiotics, and Synbiotics on CD4 Counts in HIV-Infected Patients: A Systematic Review and Meta-Analysis. Fu, YS., Chu, QS., Ashuro, AA., et al.[2022]

Current research indicates that while gut microbiota disturbances are linked to cardiovascular disease in HIV-infected individuals, there is a lack of clinical trials directly assessing the impact of prebiotics, probiotics, symbiotics, and fecal transplantation on reducing cardiovascular disease risk in these patients.

The review of 38 clinical trials highlights significant variability in the types, doses, and durations of these interventions, making it challenging to establish clear guidelines for their use in clinical practice.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lights and Shadows of Microbiota Modulation and Cardiovascular Risk in HIV Patients. Villoslada-Blanco, P., Pérez-Matute, P., Oteo, JA.[2021]

Current evidence from 16 clinical studies, including randomized control trials, does not support the use of probiotics to reduce inflammation in people living with HIV, as no consistent improvements were observed in inflammation markers or CD4 counts.

While some studies suggested potential benefits of probiotics, the overall results were inconsistent, indicating that further research is needed to explore their effects in ART-treated individuals at high risk for inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotics to manage inflammation in HIV infection. Reikvam, DH., Meyer-Myklestad, MH., Trøseid, M., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11718315/

Current trends and future directions in probiotics research ... Klatt et al. (2021) investigated whether probiotic intervention could enhance the immunogenicity and protective efficacy of SIV/HIV vaccines.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02448238

Pilot Study of Oral Probiotic Bacteria Supplementation to ... These bacterial products can overstimulate the immune system leading to increased inflammation and HIV disease progression. The investigators will investigate ...

3. discoveries.vanderbilthealth.com discoveries.vanderbilthealth.com/2022/05/probiotics-may-reduce-cardiovascular-risk-for-heavy-drinking-hiv-patients/

Probiotics may Reduce Cardiovascular Risk for Heavy ... A two-part study to determine whether probiotics can help reduce cardiovascular risk among people with HIV who are heavy drinkers.

4. withpower.com withpower.com/trial/phase-alcohol-drinking-5-2022-96dcd

Probiotics for Cardiovascular Disease in HIV+ Individuals In a study of 45 HIV-infected individuals, taking the probiotic Lactobacillus rhamnosus GG (LGG) for 8 weeks significantly reduced intestinal inflammation, as ...

5. researchgate.net researchgate.net/publication/392490396_The_Effects_of_High-Dose_Probiotic_Supplementation_on_Immune_Activation_and_Neurocognitive_Disorders_in_People_Living_with_HIV_Undergoing_Successful_Antiretroviral_Treatment_The_Procog_Study

(PDF) The Effects of High-Dose Probiotic Supplementation ... The Effects of High-Dose Probiotic Supplementation on Immune Activation and Neurocognitive Disorders in People Living with HIV Undergoing ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5718258/

Gut microbial diversity in HIV infection post combined ... Data from recent clinical trials aiming to evaluate the tolerability and efficacy of probiotics in treated HIV+ patients are promising and support a significant ...

7. medsites.vumc.org medsites.vumc.org/v-polaris/meta-clinical-trial

META Clinical Trial | V-Polaris META HIV CVD​​ The goals of this research are to determine if: A tailored probiotic (i.e., contains bacteria supporting butyrate synthesis) can mitigate alcohol ...