The Path Study: Cognitive and Inflammation Targeted Gut-brain Interventions in Alcohol; Probiotics, Alcohol, Transcutaneous Vagus Nerve Stimulation, and HIV Study

Study Overview
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Brief Summary
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This project uses a hybrid trial design to evaluate two biomedical interventions targeting the gut-brain axis. One intervention is portable Transcutaneous Vagus Nerve Stimulator, tVNS, that is hypothesized to stimulate the autonomic nervous system, resulting in decreased inflammation and improved cognition. The second intervention is a probiotic supplement intended to replace gut bacteria that are associated with dysbiosis in persons with HIV and alcohol consumption.

Official Title
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Cognitive and Inflammation Targeted Gut-brain Interventions in Alcohol; Probiotics, Alcohol, Transcutaneous Vagus Nerve Stimulation, and HIV Study

Conditions
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Cognition, Gut Microbiome

Intervention / Treatment
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* Dietary Supplement: Probiotic Supplement
* Device: Transcutaneous Vagal Nerve Stimulation (tVNS)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 35-70 years English or Spanish speaking Alcohol users Cognitive impairment Current CD4>350 Exclusion Criteria: Diagnosed major psychiatric illness Consumption of over 300 drinks in the past 30 days Recent opioid use Lifetime history of medically-assisted alcohol detoxification Inpatient or intensive treatment for addictive behaviors in the past 12 months MRI contraindications Current antibiotic treatment Current probiotic use Physical impairment precluding motor response or lying still.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Factorial Assignment
Interventional Model Description: This is a 2 x 2 factorial, longitudinal design (tVNS/Sham, Probiotic/Placebo) across three time points (baseline; 30days and 90days).
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dietary Supplement (e.g., vitamins, minerals)<br>Visbiome probiotic supplement | Dietary Supplement: Probiotic Supplement<br>* Participants will take a probiotic supplement or placebo for 90 days.<br>|
| Active Comparator: Device (including sham)<br>Transcutaneous Vagal Nerve Stimulation (tVNS) | Device: Transcutaneous Vagal Nerve Stimulation (tVNS)<br>* Participants will use a non-invasive stimulator 1 hour daily for 30 days. This stimulator is placed around the ear similar to headphones and produces a very mile electric current. This wellness device is safe to use and painless. Some describe the sensation to be a slight tingle up to a small itch.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Improved cognition from day 1 to day 90 | Various indices of cognition will be measured using standard neuropsychological tests and neuroimaging at multiple time points and examined for change within subjects. | Baseline up to 90 days | 
| Reduction of dysbiosis from day 1 to day 90 | The gut microbiome will be analyzed through stool samples to measure for changes in biodiversity including an increase in beneficial bacteria. | Baseline up to 90 days |