Effects of Ketones on Brain Energetics and Alcohol Consumption in Alcohol Use Disorder

NCT06807918 | Not Yet Recruiting Phase 2 DMC

• 2 other identifiers: 8574931R01AA031570-01A1
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind, crossover trial to evaluate the immediate effects of a nutritional ketone supplement, Kenotic compared to placebo on brain function and alcohol consumption in individuals with alcohol use disorder. Participants will complete 2 MRI scans, 2 FDG PET/CT scans, and 2 alcohol bar labs and will randomly receive Kenetik at one lab and the placebo at the next lab. During the bar labs participants will consume a dose of alcohol (based on weight), to bring their breath alcohol concentration to about 0.050%.

Conditions

Alcohol Use Disorder; Ketosis

Keywords

Alcohol Use Disorder; Ketosis; Ketone supplement; Magnetic Resonance Spectroscopy

Outcome Measures

Primary Outcomes (2)

• To examine the effects of a single dose of KS compared to placebo on brain glucose energetics

  The primary outcome measure to be analyzed is a comparison of a single dose of KS versus placebo in AUD subjects in the amount of FDG uptake (CMRg metabolic rate of glucose) (mmol/L) levels in the brain.

  90 minutes

• To examine the effects of a single dose of KS compared to placebo on brain ketone energetics

  The primary outcome measure to be analyzed is a comparison of a single dose of KS versus placebo in AUD subjects in the amount of FDG uptake BHB (beta-hydroxybutyrate) (mmol/L) levels in the brain.

  90 minutes

Secondary Outcomes (2)

• To determine the effects of KS compared to placebo on alcohol pharmacokinetics and subjective responses following an alcohol priming dose.

  3 hours

• To determine the effects of KS compared to placebo on alcohol consumption.

  2 hours

Study Arms (3)

Ketone Supplement, Kenetik

ACTIVE COMPARATOR

Kenetik: Ketone Drink supplement containing D-beta-hydroxybutyric acid and R-1,3 butanediol. D-beta-hydroxybutyric acid (C4H8O3) and 1,3 butanediol (C4H10O2). We will give 25 g of ketones 3 times. Once at an MRI visit, once at an FDG PET/CT scan visit, and once at an alcohol bar lab visit.

Other: magnetic resonance imaging scan; Other: fludeoxyglucose-18 positron emission tomography scan; Other: Alcohol bar lab

Placebo Beverage

PLACEBO COMPARATOR

Taste-matched placebo beverage is given 3 times. Once at an MRI visit, once at an FDG PET/CT scan visit, and once at an alcohol bar lab visit.

Other: magnetic resonance imaging scan; Other: fludeoxyglucose-18 positron emission tomography scan; Other: Alcohol bar lab

Alcohol beverage

EXPERIMENTAL

The alcoholic beverage will be created by using a standard dose of 0.5g/kg 0.43 g/kg for men and women respectively (50% vodka), calculated to achieve a BrAC of about 0.050%. The alcoholic beverage will be given once at bar lab 1 and again at bar lab 2.

Dietary Supplement: Kenetik; Other: Placebo beverage

Interventions

Kenetik DIETARY_SUPPLEMENT

Drink a single dose of ketone supplement 25g, three times, randomly given at 1 of 2 MRI scan visits, 1 of 2 FDG PET/CT scan visits, and 1 of 2 alcohol bar lab visits.

Also known as: D-Beta-hydroxybutyric acid and R-1,3 butanediol, Ketone supplement

Alcohol beverage

magnetic resonance imaging scan OTHER

Each subject will undergo 2 research MRI scan evaluations of the brain (up to 90 min.). The MRI is FDA-approved 7.0T Magentom Prisma scanner (Siemens Medical Solutions USA, Inc., Malvern, PA) with an approved radiofrequency head coil.

Also known as: MRI scan

Ketone Supplement, Kenetik; Placebo Beverage

fludeoxyglucose-18 positron emission tomography scan OTHER

Each subject will undergo 2 FDG PET/CT scans. FDG is a positron emitting radiopharmaceutical. In addition to the radioactive FDG tracer, a low-dose CT of the chest is typically performed with the FDG PET/CT for the purpose of anatomical registration and attenuation correction of PET images. There are no separate diagnostic CT scans performed as part of this study.

Also known as: FDG PET/CT scan

Ketone Supplement, Kenetik; Placebo Beverage

Alcohol bar lab OTHER

Each subject will undergo 2 alcohol bar labs. Subjects will drink about 2 ½ standard alcohol beverages, based on their weight to reach a breath alcohol level of 0.050%.

Also known as: Alcoholic beverages

Ketone Supplement, Kenetik; Placebo Beverage

Placebo beverage OTHER

Drink a single dose of placebo beverage, that will look and taste the same as the ketone supplement. Subjects will recieve the beverage three times, randomly given at 1 of 2 MRI scan visits, 1 of 2 FDG PET/CT scan visits, and 1 of 2 alcohol bar lab visits, opisite of the Kenetik beverage.

Alcohol beverage

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21-65 years old
• Able to provide written informed consent
• Meets current DSM-5 criteria for mild to moderate (established using MINI)
• Average weekly alcohol consumption of at least 15 standard drinks over the past month before consent (self-report)
• Not seeking treatment for AUD (self-report)

You may not qualify if:

• Unwilling or unable to refrain from use of alcohol, within 24 hours of Alcohol Bar Lab, MRI and PET procedures (self-report, breathalyzer).
• Use of psychoactive medications or medications that may affect study results (self-report, medical history).
• Current DSM-5 diagnosis of a major psychiatric disorder (other than alcohol, Marijuana, and nicotine use disorders) that required hospitalization or daily medication in the past year.
• Current significant alcohol withdrawal symptoms in the past 12 months that required medical treatment (self-report, medical history).
• A current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation that could interfere with study participation or make it hazardous for the subject to do so (e.g., bleeding disorder, pancreatitis, epilepsy, liver disease, kidney disease, or diabetes as determined by history and clinical exam); ALAT or ASAT concentration greater than 3 times the upper limit of normal (ULN), or bilirubin above the ULN. (Note-abnormal laboratory tests during screening may be repeated once).
• Current, major gastrointestinal (GI) diseases, such as: GERD, Crohn's disease, Irritable bowel syndrome, Ulcerative colitis, Celiac disease Diverticulitis, or other clinically significant physical disease that may interfere with the intake of the Ketone Supplement based on medical history, and evaluation of the Study Physician.
• Clinically significant laboratory findings that could affect brain function (e.g., HIV+).
• Head trauma with loss of consciousness for more than 30 minutes (self-report, medical history).
• Pregnant or breast-feeding
• Weight greater than 250lbs (Need to cap amount of alcohol give based on weight to individuals).
• BMI greater than 35.
• Self-reported claustrophobia.
• Contraindications to MRI (e.g., metal in the body that cannot be removed and is not MRI compatible).

Sponsors & Collaborators

• University of Pennsylvania: lead
• National Institute on Alcohol Abuse and Alcoholism (NIAAA): collaborator

Study Sites (1)

Center for Studies of Addiction

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Alcoholism; Ketosis

Interventions

Magnetic Resonance Spectroscopy; Ethanol; Alcoholic Beverages

Condition Hierarchy (Ancestors)

Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Acidosis; Acid-Base Imbalance; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Spectrum Analysis; Chemistry Techniques, Analytical; Investigative Techniques; Alcohols; Organic Chemicals; Beverages; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages

Study Officials

• Corinde Wiers, Ph.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy Pond, MPH

CONTACT

215-746-1959; timpond@Pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The participant, investigator, and study staff assessing participant outcomes will all be blinded to the study intervention during the study. The placebo beverage will look and taste like Kenetik. The bottle labeling on the Kenetik and Placebo will look the same. A designated unblinded staff member will be assigned to manage the IP ordering, storage, accountability, and participant randomizations.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: There are 6 study visits in this study, 2 MRI visits, 2 FDG PET/CT scan visits, and 2 alcohol bar lab visits. Participants will randomly receive the Kenetik or placebo beverage at the first MRI visit, FDG PET/CT visit, and alcohol bar lab visit, and then the other intervention at the other visit.

Study Record Dates

• First Submitted: January 27, 2025
• First Posted: February 4, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2029
• Study Completion (Estimated): December 1, 2030
• Last Updated: May 6, 2026

Record last verified: 2026-05

Locations

US (1)