Metabolism in the Human Brain Following Consumption of a Keto-ester in Alcohol Use Disorder (AUD) With Proton Magnetic Resonance Spectroscopic Imaging (MRSI)

The objective of this study is to determine whether BHB levels in the brain will be positively associated with alcohol consumption, due to hypothesized enhancement of BHB transport into the brain.

Study Overview

• Status: Completed
• Conditions: Alcohol Use Disorder; BHB Transport
• Intervention / Treatment: Other: Keto-ester followed by Magnetic Resonance Spectroscopic Imaging (MRSI) scans

Detailed Description

The primary objective of this study is to determine whether BHB levels in the brain will be positively associated with alcohol consumption, due to hypothesized enhancement of BHB transport into the brain. Furthermore, BHB levels in identified brain regions will be compared against measures of craving.

The secondary objective of this study is to investigate if GABA levels will be elevated in key brain regions relative to the baseline scan in AC subjects due to preferential BHB metabolism. The goal is to acquire preliminary data to apply for an R01 or equivalent grant submission to pursue this metabolic therapy in greater detail using the state-of-the-art MRSI platform at Yale University to study alcohol use disorders.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • New Haven, Connecticut, United States, 06519
      • The Anlyan Center (TAC)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• For AUD patients: individuals assessed to be with mild to - medium severity according to the DSM-5 criteria.
• For non-dependent heavy at-risk drinkers: must be Individuals who consume more than 14 drinks per week for men or more than 8 drinks per week for women, for at least the last 2 months.
• For healthy controls: must be light drinkers not dependent on alcohol, who consume fewer than 2 drinks per week for at least the last 6 months.
• English speaking
• Can read and understand a study the consent form

Exclusion Criteria:

• Non-English speaking
• Unable to read and understand the consent form
• History of alcohol withdrawal in the last 12 months. This will reduce chances of a volunteer having withdrawal symptoms in the middle of the experiment.
• Participants with a history of psychiatric conditions (that include PTSD, schizophrenia, and bipolar disorders), or a history of neurological conditions
• Women who test positive on a pregnancy test collected on either the screening visit or day of the study.
• Healthy subjects identified with substance use with the exception of tobacco and alcohol will be excluded.
• AC subjects identified with substance use, with the exception of tobacco, alcohol, and mild cannabis use disorder (based on the DSM-5 criteria during the medical history) in the last 6 months, will be excluded.
• Persons unable to refrain from alcohol use for 48 hours and undergo a 10-hour fast prior to the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Alcohol consumer (AC) participants; Adult volunteers who are alcohol consumers drawn from both an outpatient population and recruited heavy drinkers from the community.	Other: Keto-ester followed by Magnetic Resonance Spectroscopic Imaging (MRSI) scans; Following baseline scans, the participant will orally consume the keto-ester, for subsequent scans which will include repeated BHB MRSI acquisitions to dynamically measure BHB labeling in the brain, followed by a final GABA MRSI acquisition.
Other: Healthy participants; Healthy adult volunteers who are not dependent on alcohol.	Other: Keto-ester followed by Magnetic Resonance Spectroscopic Imaging (MRSI) scans; Following baseline scans, the participant will orally consume the keto-ester, for subsequent scans which will include repeated BHB MRSI acquisitions to dynamically measure BHB labeling in the brain, followed by a final GABA MRSI acquisition.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in BHB levels in the brain	β-hydroxybutyrate blood levels in the brain will be assessed via MRSI.	Approximately 90 minutes after Baseline Assessment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in GABA levels in the brain	GABA levels will be assessed in the brain via MRSI to determine if they are elevated in key brain regions relative to the baseline scan.	Approximately 90 minutes after Baseline Assessment

Collaborators and Investigators

• Sponsor: Yale University
• Investigators: Principal Investigator: Chathura Kumaragamage, PhD, Bioimaging SciencesMagnetic Resonance SpectroscopyRadiology & Biomedical Imaging

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Actual): May 15, 2024
• Study Completion (Actual): May 15, 2024

Study Registration Dates

• First Submitted: June 30, 2023
• First Submitted That Met QC Criteria: June 30, 2023
• First Posted (Actual): July 10, 2023

Study Record Updates

• Last Update Posted (Estimated): December 11, 2024
• Last Update Submitted That Met QC Criteria: December 10, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: AUD; BHB
• Additional Relevant MeSH Terms: Mental Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Drinking Behavior; Alcohol-Related Disorders; Alcoholism; Alcohol Drinking
• Other Study ID Numbers: 2000035050; 000 (Other Identifier: YCTG)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified data from this study be submitted to the NIMH data archive (NDA) at the NIH.
• IPD Sharing Time Frame: Following study completion and final funder reporting obligations.

Drug and device information, study documents

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