Effects of Ketone Supplementation on Alcohol Withdrawal and Brain Metabolism in Alcohol Use Disorder

NCT ID: NCT06559995

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 30 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-08-01
• Study Completion Date: 2027-12-31

Brief Summary

The goal of this clinical trial is to learn the effects of ketone supplement compared to placebo on alcohol withdrawal symptoms during a 4 day alcohol withdrawal management treatment in adults with moderate to severe alcohol use disorder at the Hospital of the University of Pennsylvania, Cedar Detox Center.

Detailed Description

This is a 4-day randomized double-blinded intervention study of 30 treatment seeking adults with alcohol use disorder, who are receiving alcohol detoxification treatment at the Hospital of the University of Pennsylvania, Cedar Detox Center. Within 24 hours of admission to the inpatient unit, participants will be consented and randomized to receive 3x daily of 12g of KS (n=15; 1,3-butanediol and D-hydroxybutyric acid from Kenetik, VitaNav Inc., Washington D.C.) for 4 days or placebo beverage (n=15). Benzodiazepines and other "comfort" medications will be administered daily following the HUP Cedar withdrawal management protocol, with benzodiazepines administered based on withdrawal symptoms, monitored with the revised Clinical Institute Withdrawal Assessment for Alcohol. The revised Clinical Institute Withdrawal Assessment for Alcohol is given three or more times a day clinically to determine patient withdrawal levels and adjust medication dosages. Total daily maximum revised Clinical Institute Withdrawal Assessment for Alcohol scores, benzodiazepine dosage, and other "comfort" medications will be analyzed with a repeated measures design, with a binary factor for intervention, factor of time, and intervention by time interaction. Daily mood questions and alcohol craving questions will assess differences between treatment groups. After 4 days of study intervention, all participants will undergo an approximately 1.5-hr. magnetic resonance imaging session.

Conditions

Alcohol Use Disorder; Alcohol Withdrawal; Ketosis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: TRIPLE

Study Groups

Ketone Supplement

Ketone supplement "D-beta-hydroxybutryric acid and R-1,3 butanediol" (Kenetik: Ketone Drink, VitaNav Inc., Washington D.C.) 12g of ketones, three times a day before meals, by mouth for 4 days plus 1 dose on day 5 for magnetic resonance imaging session visit.

Group Type: EXPERIMENTAL

ketone supplement "D-beta-hydroxybutryric acid and R-1,3 butanediol" 12g of ketones,

Intervention Type: DIETARY_SUPPLEMENT

ketone supplement

magnetic resonance imaging session

Intervention Type: DIAGNOSTIC_TEST

1.5 hour magnetic resonance imaging session

Placebo Beverage

Placebo beverage, visually matched, three times a day before meals, by mouth for 4 days plus 1 dose on day 5 for magnetic resonance imaging session visit.

Group Type: PLACEBO_COMPARATOR

magnetic resonance imaging session

Intervention Type: DIAGNOSTIC_TEST

1.5 hour magnetic resonance imaging session

Placebo beverage

Intervention Type: DIETARY_SUPPLEMENT

Placebo beverage, visually matched, three times a day before meals, by mouth for 4 days plus 1 dose on day 5 for magnetic resonance imaging session visit.

Interventions

ketone supplement "D-beta-hydroxybutryric acid and R-1,3 butanediol" 12g of ketones,

ketone supplement

Intervention Type: DIETARY_SUPPLEMENT

magnetic resonance imaging session

1.5 hour magnetic resonance imaging session

Intervention Type: DIAGNOSTIC_TEST

Placebo beverage

Placebo beverage, visually matched, three times a day before meals, by mouth for 4 days plus 1 dose on day 5 for magnetic resonance imaging session visit.

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

Kenetik: Ketone Drink, VitaNav Inc., Washington D.C.; MRI; Placebo

Eligibility Criteria

Inclusion Criteria

1. Able to communicate English and provide written informed consent

2. Meets current DSM-5 criteria for moderate or severe AUD and seeking treatment for AUD

3. Minimum 3-year history of heavy drinking (self-report).

4. Presence of alcohol withdrawal (DSM-5)

Exclusion Criteria

1. Current DSM-5 diagnosis of a major psychiatric disorder (other than alcohol and nicotine use disorders) that would interfere with study procedures.

2. Major medical problems that could impact brain function or the use of a Ketone supplement (e.g., epilepsy or diabetes) as determined by history and physical exam.

3. Clinically significant laboratory findings that could affect brain function (e.g., HIV+)

4. Head trauma with loss of consciousness for more than 30 minutes,

5. Pregnant or breast-feeding

6. BMI greater than 35

7. Self-reported claustrophobia

8. Contraindications to MRI (e.g., metal in the body that cannot be removed).

9. Current, gastrointestinal (GI), liver 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.

10. Current significant withdrawal from other substances, including benzodiazepines, opioids that require medication management for withdrawal and may interfere with study results/withdrawal management plan.

11. Judged by the principal investigator, Study Physician, or their designee to be an unsuitable candidate for the study.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

NIH

Sponsor Role: collaborator

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Corinde Wiers, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

Center for Studies of Addiction

Philadelphia, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Timothy Pond, MPH

Role: CONTACT

timpond@pennmedicine.upenn.edu

215-746-1959

Facility Contacts

Timothy Pond, MPH

Role: primary

timpond@pennmedicine.upenn.edu

215-746-1959

Other Identifiers

5R21AA031337

Identifier Type: NIH

Identifier Source: secondary_id

View Link

856689

Identifier Type: -

Identifier Source: org_study_id