Gut Microbiota-Mediated Inflammatory Interactions Between AUD and HIV Infection
1 other identifier
interventional
40
1 country
1
Brief Summary
Alcohol use disorder (AUD) has been associated with high prevalence of inflammation-associated co-morbidities in people living with HIV even those receiving effective antiretroviral therapy (ART). Our preliminary data support a model in which the combined insult of AUD and HIV on the gut, specifically on the microbiota and intestinal barrier integrity, exacerbates inflammation. Our preliminary data using intestinal organoids also suggest a potential mechanism for AUD-mediated changes in the gut barrier function during HIV; the intestines of HIV+ individuals have low resilience to alcohol induced intestinal barrier disruption caused by high levels of oxidative stress. Finally, our preliminary data also suggest a potential approach to enhance the integrity of the intestinal barrier and reduce gut derived inflammation in people living with HIV with/without AUD- short chain fatty acid prebiotics. These prebiotics prevent alcohol mediated adverse effects on the intestinal barrier and inflammation by preventing oxidative stress. These prebiotics are safe and decrease gut inflammation in humans. 40 HIV+ ART+ (20 AUD- and 20 AUD +), will be recruited for a prebiotic intervention. This is a proof-of-concept intervention study to establish a causal link between microbiota-gut and HIV pathology during ART by asking whether modifying microbiota and gut milieu impacts intestinal barrier function, systemic inflammation, and brain pathology in HIV+ people. Participants will complete three in-person clinic visits and four virtual check-in visits during this 8 week study. This study uses a crossover design. At baseline, participants will be randomized to receive either a prebiotic or a placebo for the first intervention period. After completing this period, participants will cross over to receive the alternate study product for the second intervention period, allowing each participant to serve as their own control. These participants are part of the larger observation study (n=160), which will test the hypothesis that intestines from HIV+ individuals have lower resilience to alcohol mediated gut barrier disruption than intestines from HIV-negative controls. New participants will also be recruited. Blood, urine, and stool, will be collected from participants to compare intestinal barrier integrity, system and gut inflammation, immune activation, oxidative stress, microbiome/metabolome. and HIV reservois.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for not_applicable
Started Mar 2024
Longer than P75 for not_applicable
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 14, 2023
CompletedFirst Posted
Study publicly available on registry
November 18, 2023
CompletedStudy Start
First participant enrolled
March 5, 2024
CompletedPrimary Completion
Last participant's last visit for primary outcome
August 31, 2028
ExpectedStudy Completion
Last participant's last visit for all outcomes
August 31, 2029
June 4, 2026
June 1, 2026
4.5 years
November 14, 2023
June 2, 2026
Conditions
Outcome Measures
Primary Outcomes (1)
Sugar test for intestinal permeability after prebiotic and placebo consumption in substudy
Measure the permeation of sugar probes following an oral test dose of sugars as this is standard for evaluating intestinal barrier integrity
8 weeks
Secondary Outcomes (2)
Change in stool and intestinal microbiota composition after prebiotic and placebo consumption
8 weeks
Change in plasma and stool SCFA level before and after prebiotic treatment
8 weeks
Study Arms (2)
HIV-infected ART-suppressed individuals with AUD
EXPERIMENTALOnly 20 HIV+ ART+,AUD + individuals will be invited to take part in a prebiotic sub study, which they will take a prebiotic for 4 weeks and placebo for 4 weeks.
HIV-infected ART-suppressed individuals with no AUD
EXPERIMENTALOnly 20 HIV+ ART+,AUD - individuals will be invited to take part in a prebiotic sub study, which they will take a prebiotic for 4 weeks and placebo for 4 weeks.
Interventions
For this crossover design, participants will be randomly assigned to take a prebiotic or placebo for 4 weeks and then switch to the other products. Participants and research coordinators will be blinded. Participants will be instructed to consume the prebiotic daily during the first three days and then twice daily for the remaining weeks. Participants will be instructed to consume the powder in the morning on the first three days, then in the morning and afternoon for the following weeks. They will record their prebiotic consumption and gastrointestinal symptoms in a daily log and have weekly check-ins with the research coordinator.
For this crossover design, participants will be randomly assigned to take a prebiotic or placebo for 4 weeks and then switch to the other products. Participants and research coordinators will be blinded. Participants will be instructed to consume the placebo (maltodextrin) daily during the first three days and then twice daily for the remaining weeks. Participants will be instructed to consume the powder in the morning on the first three days, then in the morning and afternoon for the following weeks. They will record their prebiotic consumption and gastrointestinal symptoms in a daily log and have weekly check-ins with the research coordinator.
Eligibility Criteria
You may qualify if:
- Age 21 to 75 years men and women
- Infection with HIV-1, as documented by a licensed ELISA and confirmed by a Western blot or HIV-1 RNA
- On ART for at least 12 months. No history of zidovudine (AZT) or stavudine (D4T) use.
- No change in ART for at least 6 months.
- CD4+ T cell count of \> 250 cells/µl, nadir CD4+ T cell count of \> 250 cells/µl
- Plasma HIV-1 RNA level consistently below the limit of detection of commercial ultrasensitive assay (usually \<20 copies/mL) for at least six months before study entry.
- For those for "AUD group" AUDIT-C =/\> 4 for men and = ≥3 for women.
- Documented BMI between 25-40
- Ability and willingness to provide informed consent
You may not qualify if:
- Receipt of a non-HIV vaccine within 30 days
- Opportunistic infection within 30 days
- Immunosuppressive medications (e.g., systemic corticosteroids, tacrolimus, sirolimus, mycophenolate, azathioprine, interferon, and cancer chemotherapy) within 90 days
- History of clinically significant medical disease that could potentially impact the integrity of intestinal barrier function or microbiota including renal (creatinine \>2 mg/dL), liver (documented cirrhosis based on histology or ALT/AST greater than 2 1/2 times normal), cardiac failure (NY classification III/IV), or uncontrolled diabetes (Hgb-A1c\>8%).
- Fiber intake \> 15 grams.
- Chronic HBV and un-treated HCV (documentation of cure can be enrolled)
- Herbal/botanical supplements with potential microbiome or anti-inflammatory effects (e.g., inulin/chicory fiber, berberine, high-dose polyphenols). Participants will be eligible to participant if they discontinue use for at least 2 weeks before enrollment.
- Regular use of medications that affect intestinal permeability including NSAIDs (daily more than three days a week during the prior two weeks). Type and frequency and duration of NSAID (those taking less than 3 /per week) should be recorded. If participants need to take antibiotics or NSAIDS during the study, duration, name, and dosage will be recorded but they will not be excluded.
- Antibiotics (during or prior) four weeks to enrollment. Type and duration of antibiotic treatment within 90 days should be recorded.
- Current use of a restrictive or specialty diet like vegan, vegetarian, gluten-free, Paleo, or any specific carbohydrate diet because these diets can impact the microbiota community.
- Use of herbal, botanical, or nutraceutical supplements with potential effects on the gut microbiome or systemic inflammation. This includes:
- prebiotic fibers such as inulin, chicory root, fructooligosaccharides (FOS), or galactooligosaccharides (GOS) botanical or herbal compounds with microbiome-modulating or anti-inflammatory properties, such as berberine, curcumin, resveratrol, or high-dose polyphenol Probiotics or synbiotics Digestive enzymes or other nutraceuticals reported to alter gut microbial composition.
- Potential participants may enroll if they discontinue use for at least 2 weeks before enrollment. Type, dosage, frequency, route of administration (for example oral), and date last taken will be documented at time of enrollment verify that a sufficient washout period has occurred before enrollment.
- Have undergone bowel preparation or colonic (e.g., for a colonoscopy or similar procedure) for example, within 4 weeks prior to enrollment.
- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease). Celiac disease. GI cancers
- +3 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Ali Keshavarzian
Chicago, Illinois, 60612, United States
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- NONE
- Masking Details
- Participants and study investigators will be blinded to treatment allocation. Prebiotic and placebo sachet powder will be identical in appearance, packaging, and labeling.
- Purpose
- BASIC SCIENCE
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Professor, Director of Center for Integrated Microbiome and Chronobiology Research
Study Record Dates
First Submitted
November 14, 2023
First Posted
November 18, 2023
Study Start
March 5, 2024
Primary Completion (Estimated)
August 31, 2028
Study Completion (Estimated)
August 31, 2029
Last Updated
June 4, 2026
Record last verified: 2026-06