Ketone supplement to reduce alcohol withdrawal symptoms and change brain metabolism

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

This will test whether a 4-day oral ketone supplement can reduce alcohol withdrawal symptoms and alter brain metabolism in adults with moderate to severe alcohol use disorder during inpatient detox.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 30 (estimated)
• Ages: 18 Years to 65 Years
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT06559995 on ClinicalTrials.gov

What this trial studies

This is a randomized, double-blind, placebo-controlled 4-day intervention enrolling 30 adults admitted for alcohol detoxification at the Hospital of the University of Pennsylvania Cedar Detox Center. Participants are randomized within 24 hours of admission to receive either 12 g ketone supplement three times daily (n=15) or a placebo beverage (n=15) while receiving standard benzodiazepine and comfort medication management guided by CIWA scores. Daily outcomes include CIWA scores, benzodiazepine dosing, mood and craving measures, analyzed with repeated measures to compare treatment groups over time. After the 4-day intervention all participants complete an approximately 1.5-hour magnetic resonance imaging session to examine effects on brain metabolism.

Who should consider this trial

Good fit: Adults who speak English, meet DSM-5 criteria for moderate or severe alcohol use disorder, have a minimum three-year history of heavy drinking, and are admitted for inpatient alcohol withdrawal management are ideal candidates.

Not a fit: People with major psychiatric disorders (other than alcohol or nicotine use disorder), epilepsy, diabetes, significant medical or laboratory abnormalities (e.g., HIV+), pregnancy or breastfeeding, BMI >35, claustrophobia, MRI contraindications, or active serious GI/liver disease would be excluded and may not benefit from this intervention.

Why it matters

Potential benefit: If successful, the ketone supplement could lessen withdrawal severity, reduce benzodiazepine requirements, and demonstrate beneficial changes in brain metabolism during early detoxification.

How similar studies have performed: Using ketone supplements specifically for alcohol withdrawal is relatively novel, though prior research has shown ketone-based therapies can alter brain metabolism and provide symptom benefits in other neurological conditions.

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.

Where this trial is running

Philadelphia, Pennsylvania

• Center for Studies of Addiction — Philadelphia, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Corinde Wiers, Ph.D. — University of Pennsylvania
• Study coordinator: Timothy Pond, MPH

Conditions Alcohol Use Disorder; Alcohol Withdrawal; Ketosis; ketosis; Ketone Supplement