Probiotic + Prebiotic for Fatty Liver in HIV/AIDS

(GLAM HIV NAFLD Trial)

Overseen By Curtis L Gabriel, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase < 1

Sponsor: Vanderbilt University Medical Center

Must be taking: Antiretrovirals

Must not be taking: Corticosteroids, Tamoxifen, Methotrexate, others

Disqualifiers: Pregnancy, Celiac, Hepatitis C, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: Unknown

Duration: 24 weeks

63 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial investigates whether a combination of probiotics (beneficial bacteria) and prebiotics (oligofructose-enriched inulin, also known as Prebiotin) can improve fatty liver disease in people living with HIV. Researchers believe changes in gut bacteria might link to fatty liver issues, and the supplements could have a positive impact. The study seeks participants who have HIV, are on stable HIV treatment, and also experience high blood sugar, high blood pressure, or have been diagnosed with fatty liver disease. As an Early Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance to be among the first to explore this potential new therapy.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does exclude those on certain medications like systemic corticosteroids, tamoxifen, and methotrexate. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that prebiotics and probiotics are generally safe for people, including those with HIV/AIDS. Studies have found that they can improve gut health without causing serious side effects. For example, one study showed that the prebiotic inulin helps protect against non-alcoholic fatty liver disease (NAFLD) by improving the interaction between the gut and liver. This can be very beneficial for people with liver problems.

Overall, using probiotics and prebiotics together is well-tolerated. Research supports their safety, but staying informed and consulting healthcare providers before starting any new treatment is always important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver in HIV?

Researchers are excited about using a combination of probiotics and prebiotics for treating fatty liver in people with HIV/AIDS because these treatments work differently from traditional medications. Unlike standard drugs that might focus on reducing fat or controlling inflammation through chemical pathways, probiotics and prebiotics aim to improve gut health by fostering beneficial bacteria. This approach not only targets liver health but also enhances overall digestive health, which can be crucial for individuals with HIV/AIDS. By improving the balance of gut microbiota, these treatments could potentially offer a more natural and holistic way to manage fatty liver disease.

What evidence suggests that this trial's treatments could be effective for fatty liver in HIV/AIDS?

This trial will evaluate the combination of probiotics and prebiotics to improve liver health in people with HIV/AIDS who face a higher risk of developing fatty liver disease. Research has shown that probiotics and prebiotics can enhance liver health in individuals with nonalcoholic fatty liver disease (NAFLD). Studies have found that these supplements can reduce liver fat, decrease inflammation, and improve liver function. Probiotics such as Lactobacillus and Bifidobacterium can increase beneficial gut bacteria, potentially reducing liver damage. In people with NAFLD, probiotics and prebiotics can also improve key health indicators like liver enzymes and cholesterol levels, suggesting they might benefit people with HIV. ^{2 4 6 7 8}

Are You a Good Fit for This Trial?

This trial is for adults with HIV who have high triglycerides, signs of metabolic syndrome, or a diagnosis of fatty liver disease. They must be on stable antiretroviral therapy with controlled HIV and not pregnant, planning pregnancy, or have other liver diseases. Participants need to speak English and have access to a private fridge.

Inclusion Criteria

Persistently abnormal transaminases: elevated liver enzymes defined by transaminases ≥1.5 upper limit of normal ([ULN] = 35 IU/mL) and/or gammaglutamyltransferase level ≥2 ULN (ULN = 60 IU/L) on 2 blood samples within at least a 3-month interval

BMI ≥ 30 kg/m2

Documented HIV infection

Exclusion Criteria

I have been diagnosed with celiac disease.

I have been diagnosed with a liver disease other than NAFLD.

I have had cirrhosis or a liver transplant.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive a probiotic containing multiple strains of bacteria supporting butyrate synthesis and prebiotic fiber

24 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Prebiotic
• Probiotic

Trial Overview The study investigates if probiotics and prebiotics can improve markers of fatty liver disease in people with HIV by altering the gut microbiome. It's testing whether these supplements can help maintain a healthy gut-liver relationship.

How Is the Trial Designed?

Group I: Probiotic and Prebiotic Fiber Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

Supplementation with prebiotics or symbiotics may lead to changes in the intestinal microbiota of patients with non-alcoholic fatty liver disease (NAFLD), based on a systematic review of four studies.

Despite these changes in gut microbiota, the current evidence does not support the clinical use of these supplements as a treatment for NAFLD due to high risk of bias in the studies reviewed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

PROBIOTIC, PREBIOTIC OR SYMBIOTIC SUPPLEMENTATION IMPACTS ON INTESTINAL MICROBIOTA IN PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE: A SYSTEMATIC REVIEW. Souza, CA., Rocha, R., Costa, PRF., et al.[2022]

In a clinical trial with 50 NASH patients, synbiotic supplementation combined with nutritional counseling led to significant reductions in liver fat (steatosis), weight loss, and decreased body measurements compared to nutritional counseling alone.

While the synbiotic treatment did not improve intestinal permeability or levels of lipopolysaccharides, it was effective in reducing steatosis, highlighting its potential as a beneficial intervention for managing NASH.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Beneficial Effect of Synbiotic Supplementation on Hepatic Steatosis and Anthropometric Parameters, But Not on Gut Permeability in a Population with Nonalcoholic Steatohepatitis. Ferolla, SM., Couto, CA., Costa-Silva, L., et al.[2022]

In a double-blind, placebo-controlled trial involving 58 type 2 diabetes patients with nonalcoholic fatty liver disease (NAFLD), the probiotic 'Symbiter' significantly reduced the fatty liver index (FLI) from 84.33 to 78.73, indicating a decrease in liver fat (p<0.001).

The probiotic treatment also led to significant reductions in serum aminotransferase levels (AST and GGT) and inflammatory markers TNF-α and IL-6, suggesting that modulating gut microbiota could be a promising new therapy for NAFLD, warranting further research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Multi-strain Probiotic Reduces the Fatty Liver Index, Cytokines and Aminotransferase levels in NAFLD Patients: Evidence from a Randomized Clinical Trial. Kobyliak, N., Abenavoli, L., Mykhalchyshyn, G., et al.[2019]

A systematic review of 105 studies involving 6826 subjects found that oral intake of probiotics led to significant improvements in metabolic risk factors for overweight individuals, including reductions in body weight, body mass index, waist circumference, body fat mass, and visceral fat.

In type 2 diabetics, probiotics were effective in lowering fasting glucose, glycated hemoglobin, insulin levels, and insulin resistance, indicating their potential role in managing diabetes and related metabolic conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials. Koutnikova, H., Genser, B., Monteiro-Sepulveda, M., et al.[2020]

The prebiotic oligofructose (OFS) significantly reduced energy intake, weight gain, and fat mass in obese rats, indicating its strong impact on body composition compared to the probiotic Bifidobacterium animalis subsp. lactis BB-12.

Both OFS and BB-12 improved glycemic control, with OFS increasing GLP-1 levels and BB-12 enhancing GLP-2 levels, highlighting the beneficial effects of both prebiotics and probiotics on metabolism.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Combined effects of oligofructose and Bifidobacterium animalis on gut microbiota and glycemia in obese rats. Bomhof, MR., Saha, DC., Reid, DT., et al.[2014]

A meta-analysis of 28 clinical trials involving 1555 patients with nonalcoholic fatty liver disease (NAFLD) showed that probiotic therapy significantly improved several health markers, including body mass index and liver enzymes, over treatment periods of 4 to 28 weeks.

Probiotics were found to be more effective than placebo in managing NAFLD, suggesting they could serve as a valuable complementary treatment option for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Systematic Review with Meta-Analysis: The Effects of Probiotics in Nonalcoholic Fatty Liver Disease. Xiao, MW., Lin, SX., Shen, ZH., et al.[2022]

In a study involving 75 patients with non-alcoholic fatty liver disease (NAFLD), supplementation with probiotics and/or prebiotics significantly reduced body weight, body mass index, waist and hip circumferences, and inflammatory markers like tumor necrosis factor-α compared to a placebo.

The combination of probiotics and prebiotics was particularly effective in lowering high-sensitive C-reactive protein (hs-CRP), indicating enhanced anti-inflammatory effects, while no significant differences were found between the individual and combined treatments for other oxidative stress markers.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Pro- and prebiotic effects on oxidative stress and inflammatory markers in non-alcoholic fatty liver disease. Javadi, L., Khoshbaten, M., Safaiyan, A., et al.[2019]

In a study involving 72 patients with nonalcoholic fatty liver disease (NAFLD), consuming probiotic yogurt for 8 weeks led to significant reductions in liver enzymes and cholesterol levels, indicating potential benefits for managing NAFLD.

Specifically, the probiotic yogurt reduced alanine aminotransferase and aspartate aminotransferase levels by approximately 4.67% and 5.42%, respectively, and lowered total cholesterol and LDL cholesterol by 4.1% and 6.92%, suggesting it may help improve metabolic factors associated with NAFLD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of probiotic yogurt consumption on metabolic factors in individuals with nonalcoholic fatty liver disease. Nabavi, S., Rafraf, M., Somi, MH., et al.[2022]

Probiotic supplementation significantly reduced liver enzymes (ALT, AST, GGT) and triglyceride levels in patients with nonalcoholic fatty liver disease (NAFLD) compared to a control group, indicating its potential efficacy in improving liver health.

Prebiotic supplementation also showed beneficial effects on liver enzymes and lipid profiles, suggesting that both probiotics and prebiotics may help manage metabolic parameters in NAFLD patients, although no significant differences were found between the groups after the intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of probiotic and prebiotic supplementation on metabolic parameters, liver aminotransferases, and systemic inflammation in nonalcoholic fatty liver disease: A randomized clinical trial. Behrouz, V., Aryaeian, N., Zahedi, MJ., et al.[2020]

In a study using fecal cultures from healthy and morbidly obese adults, different prebiotics were tested, revealing that 1-kestose had the most significant impact on gut microbiota composition and metabolic activity.

Prebiotic modulation led to increased Bacteroides and Faecalibacterium in obese individuals, while normal-weight individuals showed higher levels of Bifidobacterium and Faecalibacterium, highlighting the need for tailored prebiotic treatments based on individual microbiota profiles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

In Vitro Evaluation of Different Prebiotics on the Modulation of Gut Microbiota Composition and Function in Morbid Obese and Normal-Weight Subjects. Nogacka, AM., Salazar, N., Arboleya, S., et al.[2023]

In a pilot study involving 44 participants, including untreated HIV+ patients and those on antiretroviral therapy, a 6-week prebiotic intervention significantly improved gut microbiota composition, particularly in untreated HIV+ individuals, reducing HIV-associated dysbiosis.

The intervention led to declines in markers of bacterial translocation and T-cell activation, along with increased butyrate production, suggesting that targeting the bacterial butyrate synthesis pathway could be a promising strategy for improving immune function in HIV patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effects of prebiotics on microbial dysbiosis, butyrate production and immunity in HIV-infected subjects. Serrano-Villar, S., Vázquez-Castellanos, JF., Vallejo, A., et al.[2023]

In a study involving 30 obese women over 3 months, treatment with inulin-type fructans (ITF prebiotics) significantly altered gut microbiota composition, increasing beneficial bacteria like Bifidobacterium and Faecalibacterium prausnitzii, which are linked to lower serum lipopolysaccharide levels.

The ITF prebiotics also resulted in a slight decrease in fat mass and changes in plasma metabolites, suggesting that these prebiotics can modestly influence host metabolism and may have implications for obesity and diabetes management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Insight into the prebiotic concept: lessons from an exploratory, double blind intervention study with inulin-type fructans in obese women. Dewulf, EM., Cani, PD., Claus, SP., et al.[2022]

A 6-week prebiotic supplementation significantly improved the gut microbiota in HIV-infected individuals, especially in viremic untreated patients, by increasing the diversity and abundance of active bacteria with beneficial properties.

The prebiotics not only reduced dysbiosis but also enhanced the presence of immunomodulatory bacteria, such as Bifidobacteriaceae, to levels comparable to healthy individuals, indicating a potential therapeutic strategy for managing gut health in HIV patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of HIV, antiretroviral therapy and prebiotics on the active fraction of the gut microbiota. Deusch, S., Serrano-Villar, S., Rojo, D., et al.[2019]

In a 3-year observational study involving 68 participants consuming probiotic yogurt and 82 control participants, yogurt consumption was linked to a significant increase in CD4 count, with an average increase of 0.28 cells/μL/day after starting the yogurt (P=0.003).

The study suggests that probiotic yogurt can enhance immune function in people living with HIV/AIDS, as the increase in CD4 count remained significant even after adjusting for antiretroviral medication use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Probiotic yogurt consumption is associated with an increase of CD4 count among people living with HIV/AIDS. Irvine, SL., Hummelen, R., Hekmat, S., et al.[2022]

Citations

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Probiotic + Prebiotic for Fatty Liver in HIV/AIDS Trial Overview The study investigates if probiotics and prebiotics can improve markers of fatty liver disease in people with HIV by altering the gut microbiome.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10312326/

Probiotics, prebiotics, and synbiotics in nonalcoholic fatty ... Probiotic treatment with Lactobacillus and Bifidobacterium increases fecal butyrate concentrations and alleviates systemic adiposity, inflammation, and liver ...

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The effects of supplementation of probiotics, prebiotics, or ... Probiotics, prebiotics, and synbiotics supplementation can potentially improve liver enzymes, lipid profiles, and liver steatosis in patients with NAFLD.

4. mdpi.com mdpi.com/1422-0067/23/15/8805

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Research progress on probiotics and prebiotics in the... Specifically, this probiotic not only ameliorated the liver steatosis but also reduced the liver injury and mitigated insulin resistance in the affected rats.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10573697/

Therapeutic Tools for Nonalcoholic Fatty Liver Disease Alterations in the gut–liver axis and changes in the gut microbiome are among the risk factors for the pathogenesis of non-alcoholic fatty ...

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S221242922401109X

A mini-review on prebiotic inulin to prevent and treat non- ... The use of the prebiotic inulin has been shown to protect against NAFLD by targeting the gut-liver axis. In this mini-review, we present an overview of the ...

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Optimal probiotic combinations for treating nonalcoholic ... Probiotic Bifidobacterium lactis V9 attenuates hepatic steatosis and inflammation in rats with non-alcoholic fatty liver disease. Amb Express ...