Clinical trial NCT06559995: Effects of Ketone Supplementation on Alcohol Withdrawal and Brain Metabolism in Alcohol Use Disorder
Official title: Effects of Ketone Supplementation on Alcohol Withdrawal and Brain Metabolism in Alcohol Use Disorder
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Alcohol Use Disorder
Alcohol Withdrawal
Ketosis
Keywords: Alcohol Use Disorder
Alcohol Withdrawal
ketosis
Ketone Supplement
Lead sponsor: University of Pennsylvania
Sponsor class: OTHER
Collaborators: name: National Institute on Alcohol Abuse and Alcoholism (NIAAA)
First posted: 2024-08-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled, parallel-groups design clinical trial
Primary purpose: BASIC_SCIENCE

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.

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.

Primary outcomes:
measure: Group changes in the total milligrams of benzodiazepines given to subjects during alcohol withdrawal management after receiving either ketone supplement or placebo beverage after 4 days of study intervention.
timeFrame: 4 days
Secondary outcomes:
measure: To measure the group differences of BHB levels in millimoles, in subjects receiving ketone supplement, Kenetik three times daily, versus a placebo beverage after 4 days of study intervention.
timeFrame: 4 days
measure: To measure the group differences of Gamma-Aminobutyric Acid levels in millimoles in subjects receiving a ketone supplement, Kenetik three times daily, versus a placebo beverage after 4 days of study intervention.
timeFrame: 4 days
Other outcomes:
Locations:
city: Philadelphia
country: United States
facility: Center for Studies of Addiction
state: Pennsylvania
Study officials:
affiliation: University of Pennsylvania
name: Corinde Wiers, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: