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People with HIV who drink alcohol are at increased risk for accelerated aging biology, including increased immune senescence. This randomized, double-blind, crossover clinical trial evaluates two generally recognized as safe (GRAS) microbiota-targeted interventions on immune senescence biomarkers.
This is a randomized, double-blind, controlled, crossover mechanistic clinical trial in people with HIV who have recent alcohol use. Participants are randomized to receive either Limosilactobacillus reuteri probiotic or blueberry extract first for 4 weeks, followed by a 6-week washout period, then crossover to the alternate intervention for 4 weeks. Each participant receives both interventions.
Both interventions are generally recognized as safe (GRAS) dietary supplements and are not intended to diagnose, treat, cure, or prevent disease. This study is not conducted under an Investigational New Drug (IND) application and does not involve FDA-regulated investigational products.
Biospecimen collection and clinical assessments are performed at baseline and Week 4 of each intervention period. The primary analysis compares within-participant changes in immune senescence markers between interventions using a crossover design framework and accounts for period and sequence effects.
Participants will be recruited from HIV clinical care programs, affiliated clinics, and community outreach efforts in the New Orleans area.
A 6-week washout period is included to minimize potential carryover effects.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence A: Probiotic then Blueberry Extract | Experimental | Participants receive probiotic for 4 weeks, washout 6 weeks, then blueberry extract for 4 weeks. |
|
| Sequence B: Blueberry Extract then Probiotic | Experimental | Participants receive blueberry extract for 4 weeks, washout 6 weeks, then probiotic for 4 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Limosilactobacillus reuteri | Dietary Supplement | Administered as 6 capsules daily (3 twice daily) for 4 weeks. Each daily dose contains 1×10^10 CFU total in a 1:1 ratio of two strains. This is a GRAS dietary supplement and not an FDA-regulated investigational product. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in circulating senescent T cell numbers | Change in circulating CD3+CD8+CD28-CD38+ T cell count (cells/µL) during treatment period. Measured by multiparameter flow cytometry. The primary endpoint is the within-participant difference in change from baseline. | Time 0 to Week 4 of treatment period |
| Measure | Description | Time Frame |
|---|---|---|
| Change in additional senescent T cell phenotypes | Flow cytometry-defined subsets | Baseline and Week 4 |
| Change in epigenetic age estimation | Change in DNA methylation-based age estimates using epigenetic clock analyses. |
| Measure | Description | Time Frame |
|---|---|---|
| Change in additional senescent T cell phenotypes | Exploratory analyses of additional T cell phenotypes including assess additional senescence markers including lysosomal-β-galactosidase (GLB1), proinflammatory SASP (IL-1β, IL-2, IL17A, IL-18, TNFa, IFNg, HMBG1), proliferation (Ki67), CD27, CD57, and DNA damage (p-H2A.X) in T cells at multiple stages of maturation including naïve, effector, memory, and TEMRA. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| David A Welsh, MD | Contact | United States | 5045684634 | dwelsh@lsuhsc.edu |
| Name | Affiliation | Role |
|---|---|---|
| David A Welsh, MD | LSU Health New Orleans | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| LSU Health | New Orleans | Louisiana | 70112 | United States |
De-identified individual participant data will be shared upon reasonable request following publication, subject to data use agreements.
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| ID | Term |
|---|---|
| D015658 | HIV Infections |
| D000428 | Alcohol Drinking |
| ID | Term |
|---|---|
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D007239 | Infections |
| D015229 | Sexually Transmitted Diseases, Viral |
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| ID | Term |
|---|---|
| C000721609 | blueberry extract |
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Double (Participant, Investigator)
| Blueberry extract | Dietary Supplement | Administered as 6 capsules daily (3 twice daily) for 4 weeks, providing 500 mg anthocyanins per day. This is a GRAS dietary supplement and not an FDA-regulated investigational product. |
|
| Baseline and Week 4 |
| time 0 to 4 weeks |
| Microbiome and metabolite profiles | Stool microbiome (phylogenetic analysis and bacterial genes quantification) and metabolite analyses. | Baseline and Week 4 |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |
| D004327 | Drinking Behavior |
| D001519 | Behavior |