[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"trial:NCT06139224":3,"trial-entities:NCT06139224":115,"trial-summary:NCT06139224":120},{"id":4,"nct_id":4,"org_study_id":5,"brief_title":6,"official_title":7,"overall_status":8,"completion_date":9,"status_verified_date":10,"last_update_date":11,"start_date":12,"sponsor_name":13,"lead_sponsor_class":14,"has_dmc":15,"brief_summary":16,"detailed_description":15,"conditions":17,"keywords":20,"study_type":21,"primary_purpose":22,"phases":23,"enrollment_info":25,"interventions":28,"primary_outcomes":40,"secondary_outcomes":45,"sex":52,"minimum_age":53,"maximum_age":54,"healthy_volunteers":55,"eligibility_criteria":56,"std_ages":84,"locations":87,"central_contacts":103,"overall_officials":112,"references":113,"see_also_links":114},"NCT06139224","22112903","Gut Microbiota-Mediated Inflammatory Interactions Between AUD and HIV Infection","Gut Microbiota-Mediated Inflammatory Interactions Between Alcohol Use Disorders and HIV Infection","RECRUITING","2029-08-31","2026-06","2026-06-04","2024-03-05","Rush University Medical Center","OTHER",null,"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\u002Fwithout 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.\n\n40 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\u002Fmetabolome. and HIV reservois.",[18,19],"Alcohol Use Disorder","Human Immunodeficiency Virus",[],"INTERVENTIONAL","BASIC_SCIENCE",[24],"NA",{"count":26,"type":27},40,"ESTIMATED",[29,36],{"type":30,"name":31,"description":32,"armGroupLabels":33},"DIETARY_SUPPLEMENT","4 week prebiotic consumption","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.",[34,35],"HIV-infected ART-suppressed individuals with AUD","HIV-infected ART-suppressed individuals with no AUD",{"type":14,"name":37,"description":38,"armGroupLabels":39},"4 week placebo consumption","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.",[34,35],[41],{"measure":42,"description":43,"timeFrame":44},"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",[46,49],{"measure":47,"description":48,"timeFrame":44},"Change in stool and intestinal microbiota composition after prebiotic and placebo consumption","A combination of 16S rRNA gene amplicon sequencing and shotgun metagenome sequencing will be used to characterize microbial community structure in intestinal biopsies and stool.",{"measure":50,"description":51,"timeFrame":44},"Change in plasma and stool SCFA level before and after prebiotic treatment","Mass spectrometry and NMR","ALL","45 Years","75 Years",true,{"inclusion":57,"exclusion":67,"raw_text":83},[58,59,60,61,62,63,64,65,66],"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\u002Fµl, nadir CD4+ T cell count of \\> 250 cells\u002Fµl","Plasma HIV-1 RNA level consistently below the limit of detection of commercial ultrasensitive assay (usually \\\u003C20 copies\u002FmL) for at least six months before study entry.","For those for \"AUD group\" AUDIT-C =\u002F\\> 4 for men and = ≥3 for women.","Documented BMI between 25-40","Ability and willingness to provide informed consent",[68,69,70,71,72,73,74,75,76,77,78,79,80,81,82],"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\u002FdL), liver (documented cirrhosis based on histology or ALT\u002FAST greater than 2 1\u002F2 times normal), cardiac failure (NY classification III\u002FIV), or uncontrolled diabetes (Hgb-A1c\\>8%).","Fiber intake \\> 15 grams.","Chronic HBV and un-treated HCV (documentation of cure can be enrolled)","Herbal\u002Fbotanical supplements with potential microbiome or anti-inflammatory effects (e.g., inulin\u002Fchicory 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 \u002Fper 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:","Have undergone bowel preparation or colonic (e.g., for a colonoscopy or similar procedure) for example, within 4 weeks prior to enrollment.","Gastrointestinal surgeries\u002Fresection (cholecystectomy is accepted but should be recorded)","Currently taking or planning to start a GLP-1 receptor agonist or dual GLP-1\u002FGIP receptor agonist for weight loss or weight management. This includes medications such as semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), exenatide (Byetta, Bydureon), lixisenatide (Adlyxin), and tirzepatide (Mounjaro, Zepbound). Participants who previously used these medications may be eligible if they discontinued use at least 4 weeks prior to enrollment. For eligible individuals, the medication name, dosage, frequency, route of administration (for example injection or oral), and date of last dose will be documented at enrollment. The study team will document the last dose to verify that a sufficient wash out period has occurred before enrollment and to account for any possible microbiome differences.","Use of PPI is accepted but type, dose and duration should be recorded.","Inclusion Criteria:\n\n* Age 21 to 75 years men and women\n* Infection with HIV-1, as documented by a licensed ELISA and confirmed by a Western blot or HIV-1 RNA\n* On ART for at least 12 months. No history of zidovudine (AZT) or stavudine (D4T) use.\n* No change in ART for at least 6 months.\n* CD4+ T cell count of \\> 250 cells\u002Fµl, nadir CD4+ T cell count of \\> 250 cells\u002Fµl\n* Plasma HIV-1 RNA level consistently below the limit of detection of commercial ultrasensitive assay (usually \\\u003C20 copies\u002FmL) for at least six months before study entry.\n* For those for \"AUD group\" AUDIT-C =\u002F\\> 4 for men and = ≥3 for women.\n* Documented BMI between 25-40\n* Ability and willingness to provide informed consent\n\nExclusion criteria:\n\n* Receipt of a non-HIV vaccine within 30 days\n* Opportunistic infection within 30 days\n* Immunosuppressive medications (e.g., systemic corticosteroids, tacrolimus, sirolimus, mycophenolate, azathioprine, interferon, and cancer chemotherapy) within 90 days\n* History of clinically significant medical disease that could potentially impact the integrity of intestinal barrier function or microbiota including renal (creatinine \\>2 mg\u002FdL), liver (documented cirrhosis based on histology or ALT\u002FAST greater than 2 1\u002F2 times normal), cardiac failure (NY classification III\u002FIV), or uncontrolled diabetes (Hgb-A1c\\>8%).\n* Fiber intake \\> 15 grams.\n* Chronic HBV and un-treated HCV (documentation of cure can be enrolled)\n* Herbal\u002Fbotanical supplements with potential microbiome or anti-inflammatory effects (e.g., inulin\u002Fchicory fiber, berberine, high-dose polyphenols). Participants will be eligible to participant if they discontinue use for at least 2 weeks before enrollment.\n* 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 \u002Fper 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.\n* Antibiotics (during or prior) four weeks to enrollment. Type and duration of antibiotic treatment within 90 days should be recorded.\n* 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.\n* Use of herbal, botanical, or nutraceutical supplements with potential effects on the gut microbiome or systemic inflammation. This includes:\n\nprebiotic 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.\n\nPotential 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.\n\n-Have undergone bowel preparation or colonic (e.g., for a colonoscopy or similar procedure) for example, within 4 weeks prior to enrollment.\n\nInflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease). Celiac disease. GI cancers\n\n* Gastrointestinal surgeries\u002Fresection (cholecystectomy is accepted but should be recorded)\n* Currently taking or planning to start a GLP-1 receptor agonist or dual GLP-1\u002FGIP receptor agonist for weight loss or weight management. This includes medications such as semaglutide (Ozempic, Wegovy, Rybelsus), liraglutide (Victoza, Saxenda), dulaglutide (Trulicity), exenatide (Byetta, Bydureon), lixisenatide (Adlyxin), and tirzepatide (Mounjaro, Zepbound). Participants who previously used these medications may be eligible if they discontinued use at least 4 weeks prior to enrollment. For eligible individuals, the medication name, dosage, frequency, route of administration (for example injection or oral), and date of last dose will be documented at enrollment. The study team will document the last dose to verify that a sufficient wash out period has occurred before enrollment and to account for any possible microbiome differences.\n* Use of PPI is accepted but type, dose and duration should be recorded.",[85,86],"ADULT","OLDER_ADULT",[88],{"facility":89,"status":8,"city":90,"state":91,"zip":92,"country":93,"contacts":94,"geoPoint":100},"Ali Keshavarzian","Chicago","Illinois","60612","United States",[95],{"name":96,"role":97,"phone":98,"email":99},"Ali Keshavarzian, M.D.","CONTACT","312-563-4175","ali_keshavarzian@rush.edu",{"lat":101,"lon":102},41.85003,-87.65005,[104,108],{"name":105,"role":97,"phone":106,"email":107},"Michelle Villanueva, M.S.","312-942-8927","Michelle_Villanueva@rush.edu",{"name":109,"role":97,"phone":110,"email":111},"Lena DiBenedetto, B.S","312-942-9203","lena_dibenedetto@rush.edu",[],[],[],{"nct_id":4,"conditions":116,"biomarkers":119},[117,118],"Alcohol use disorder","HIV Infection",[],{"nct_id":4,"found":55,"summary":121,"prompt_version":131},{"design":122,"status":123,"heading":124,"summary":125,"follow_up":126,"word_count":127,"commitments":128,"compensation":129,"drugs_mentioned":130},"This is an interventional study with 40 planned participants. It uses a crossover design where participants will be randomly assigned to take either a prebiotic or a placebo first, then switch to the other, and both you and the research team will not know which you are taking (blinded).","completed","Gut Microbiota and Inflammation in HIV and Alcohol Use Disorder","This study is looking at how the gut (digestive system) and its bacteria (microbiota) are affected by both Alcohol Use Disorder (AUD) and HIV infection, and how this might lead to inflammation. Researchers believe that the combination of AUD and HIV can worsen inflammation by affecting the gut lining. You might be able to join if you are 21-75 years old, have HIV-1 and have been on stable antiretroviral therapy (ART) for at least 6 months. Participants will take either a prebiotic or a placebo (an inactive substance like maltodextrin) for 4 weeks, then switch to the other for another 4 weeks. The main goal is to see how these interventions affect your intestinal permeability (how easily substances pass through your gut lining) after 8 weeks. The study is currently recruiting 40 participants.","Your intestinal permeability will be measured at 8 weeks, after you have completed both the prebiotic and placebo consumption periods.",133,"You would consume either a prebiotic or a placebo daily for 4 weeks, then switch to the other for another 4 weeks. A sugar test for intestinal permeability will be conducted at 8 weeks.","Not stated in the trial record.",[],"v2"]