Acute Neural and Immune Effects of Alcohol in People Living With HIV Infection

This study will examine whether moderate alcohol use in the context of HIV infection exacerbates inflammatory signaling in the immune system and brain. The study will recruit healthy individuals and people living with HIV infection who are otherwise in good health to participate. Participants will complete an experimental protocol that involves controlled alcohol administration and magnetic resonance imaging (MRI). Primary outcomes are plasma biomarkers of inflammation and MRI markers correlated with neuroinflammation. Results will advance understanding of the effects of alcohol use in people living with HIV infection.

Study Overview

• Status: Recruiting
• Conditions: Alcohol Drinking; HIV-1-infection
• Intervention / Treatment: Other: Alcohol, ethyl, moderate dose; Other: Placebo

Detailed Description

A sample of 56 participants, to include equal numbers of PLWH and uninfected controls, will be recruited to complete the experimental protocol. Participants will be randomized to one of the two beverage conditions (0.60 g/kg alcohol beverage, 0.00 g/kg placebo beverage). Blood samples will be collected at baseline (prior to beverage administration) and for three hours afterward. Cognitive performance and subjective intoxication will be assessed using standardized measures. MRI scans will be collected 4-5 hours after beverage consumption to capture neurobiological outcomes on the descending limb of blood alcohol.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Research Assistant; Phone Number: 4018636679; Email: idresearch@lifespan.org
• Study Contact Backup: Name: Principal Investigator; Phone Number: 401-863-3491

Study Locations

• United States
  • Rhode Island
    • Providence, Rhode Island, United States, 02912
      • Recruiting
      • Brown University and The Miriam Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 21 to 60 years of age
• able to speak and read English at least at 8th grade level
• alcohol use as defined by study protocol
• body mass index of 18.5-30 kg/m2
• Lab tests obtained in past year showing no evidence of acute/chronic Hepatitis B or C infection
• HIV-1 serostatus confirmed by standard clinical testing
• HIV-specific criteria for antiretroviral medication use and lab parameters
• Able to consume soy and nuts safely

Exclusion Criteria:

• heavy drinking as defined by study protocol
• treatment for alcohol/drug use, with exception of smoking cessation
• use of specific medications in the past month
• daily use of specific over-the-counter drugs
• disorder of the lower GI tract
• positive urine drug test or screening for drug use disorder
• current major psychiatric disorder
• history of significant problems from blood draw
• safety contraindication for MRI
• head trauma with loss of consciousness > 10 min
• inability to abstain from nicotine during study session
• inability to abstain from cannabis before and during study session
• pregnant, breastfeeding, or not using effective birth control
• any other clinical condition or therapy that, in the physician's opinion, would make the individual unsuitable for study or unable to comply with dosing requirement

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Alcohol, ethyl, moderate dose; 0.6 gram ethyl alcohol per kilogram of body weight	Other: Alcohol, ethyl, moderate dose; Moderate oral dose of ethyl alcohol
PLACEBO_COMPARATOR: Placebo; 0 gram ethyl alcohol per kilogram of body weight	Other: Placebo; Placebo beverage

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Plasma biomarker of microbial translocation	Lipopolysaccharide (LPS), measured in pg/ml	0-3 hours
Plasma biomarkers of immune activation	LPS binding protein (LBP), soluble cluster of differentiation 14 (sCD14), soluble cluster of differentiation 163 (sCD163), measured in ng/ml	0-3 hours
Cerebral metabolites	Magnetic resonance spectroscopy will be used quantify cerebral metabolites in brain regions of interest. Primary metabolites of interest include the summed peak of glutamate and glutamine; glutathione; and choline.	5 hours
White matter diffusivity	Diffusion-weighted MRI will be used to quantify diffusivity metrics in brain white matter. Primary outcomes are fractional anisotropy (measured on a scale of 0-1, where 1 reflects total anisotropy), axial diffusivity (parallel to the primary axis), radial diffusivity (perpendicular to the primary axis).	5 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Subjective intoxication	Visual Analog Scale, where a higher rating indicates greater subjective feelings of alcohol intoxication	0-5 hours
Cognitive functioning	Repeatable Battery for Assessment of Neuropsychological Status standardized scores	0-2 hours

Collaborators and Investigators

• Sponsor: Brown University
• Collaborators: The Miriam Hospital; National Institute of General Medical Sciences (NIGMS)

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 19, 2021
• Primary Completion (ANTICIPATED): October 31, 2022
• Study Completion (ANTICIPATED): October 31, 2022

Study Registration Dates

• First Submitted: July 9, 2019
• First Submitted That Met QC Criteria: August 7, 2019
• First Posted (ACTUAL): August 8, 2019

Study Record Updates

• Last Update Posted (ACTUAL): September 1, 2021
• Last Update Submitted That Met QC Criteria: August 31, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: alcohol; inflammation; brain; HIV infection
• Additional Relevant MeSH Terms: Pathologic Processes; Drinking Behavior; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; Alcohol Drinking; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: 1904002429; P20GM130414 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Data generated by this study will be made available to outside investigators in accordance with NIH guidance and policies on data sharing. Data will be available in summary form and as raw individual-level data for analysis.
• IPD Sharing Time Frame: Individual-level data will be available after papers are accepted for publication.
• IPD Sharing Access Criteria: Institutions and individuals wishing to access data must contact the Principal Investigator (Peter Monti, PhD). Persons requesting data must do so in writing, identifying the affiliation and how the data will be used. Co-authorship is not required as a condition for receiving data. Users will agree that the recipient must not transfer the data to other users and that the data are only to be used for research purposes. Requestors will be required to sign a data and biospecimen sharing agreement with further stipulations for data use and security.
• IPD Sharing Supporting Information Type: ICF

Drug and device information, study documents

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