Precision Microbiota Interventions for Senoreduction Trial (PreMIS)

Geroprotective Precision Medicine Strategies in PWH That Use Alcohol

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV Infections; Alcohol Drinking; Aging; Immunosenescence
• Intervention / Treatment: Dietary supplement: Limosilactobacillus reuteri; Dietary supplement: Blueberry extract

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 160
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: David A Welsh, MD; Phone Number: 5045684634 United States; Email: dwelsh@lsuhsc.edu

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • LSU Health
      • Contact: David A Welsh, MD; Phone Number: 5045684634 United States; Email: dwelsh@lsuhsc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥40 years
• People with HIV
• Recent alcohol use defined as ≥42 grams in the prior week and positive urine ethyl glucuronide (EtG)

Exclusion Criteria:

• Probiotic use in past 3 months
• Recent antibiotics or immunosuppressives
• Allergy to study products
• Pregnancy or breastfeeding
• Inability to comply

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sequence A: Probiotic then Blueberry Extract; Participants receive probiotic for 4 weeks, washout 6 weeks, then blueberry extract for 4 weeks.	Dietary supplement: Limosilactobacillus reuteri; 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.; Dietary supplement: Blueberry extract; 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.
Experimental: Sequence B: Blueberry Extract then Probiotic; Participants receive blueberry extract for 4 weeks, washout 6 weeks, then probiotic for 4 weeks.	Dietary supplement: Limosilactobacillus reuteri; 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.; Dietary supplement: Blueberry extract; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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.	Baseline and Week 4

Other Outcome Measures

Outcome Measure	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.	time 0 to 4 weeks
Microbiome and metabolite profiles	Stool microbiome (phylogenetic analysis and bacterial genes quantification) and metabolite analyses.	Baseline and Week 4

Collaborators and Investigators

• Sponsor: Louisiana State University Health Sciences Center in New Orleans
• Investigators: Principal Investigator: David A Welsh, MD, LSU Health New Orleans

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2029

Study Registration Dates

• First Submitted: February 22, 2026
• First Submitted That Met QC Criteria: March 5, 2026
• First Posted (Actual): March 10, 2026

Study Record Updates

• Last Update Posted (Actual): March 10, 2026
• Last Update Submitted That Met QC Criteria: March 5, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Microbiome; Probiotic; Immunosenescence; Alcohol use; Senescence; Crossover trial; People with HIV; Blueberry extract
• Additional Relevant MeSH Terms: Blood-Borne Infections; Urogenital Diseases; Genital Diseases; Immune System Diseases; Infections; RNA Virus Infections; Virus Diseases; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Drinking Behavior; Behavior; HIV Infections; Alcohol Drinking; blueberry extract
• Other Study ID Numbers: 8883

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data will be shared upon reasonable request following publication, subject to data use agreements.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No