Ketone Ester Intervention in Alcohol Use Disorder

NCT04616781 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 8442354R00AA026892-02
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this research is to study how a nutritional ketone ester may effect brain function and alcohol consumption in regular alcohol users. The study will see how the brain responds, once after drinking the ketone ester and once after drinking a "placebo", which will look and taste the same as the ketone ester drink. Metabolic ketosis induced by a ketogenic diet has been previously shown to elevate brain ketone bodies and reduce alcohol withdrawal symptoms in humans with AUD, and reduce alcohol consumption in alcohol-dependent rats. The study investigates whether metabolic ketosis induced by a one-dose nutritional ketone ester (KE) reduces brain reactivity to alcohol cues (fMRI), alcohol craving and alcohol consumption in humans with AUD, and if KE elevates ketone bodies using proton spectroscopy. This study uses a double blind, random ordered, 2-way crossover design in n=20 non-treatment seeking AUD who come in on two separate testing days: on one testing day the participants consume KE ((R)-3-hydroxybutyl (R)-3-hydroxybutyrate), and on another testing day a drink with isocaloric dextrose (DEXT), after which participants are scanned for 1H-MRS and fMRI and complete an alcohol consumption paradigm each day after scanning.

Conditions

Alcohol Drinking; Alcohol Use Disorder

Keywords

Ester Keytone; MRI

Outcome Measures

Primary Outcomes (3)

• Determine the effects of ketone ester "R)-3-hydroxybutyl (R)-3-hydroxybutyrate" (KE) on alcohol consumption

  Compare the number of alcoholic drinks consumed in a "bar lab" paradigm after KE versus the Placebo drink

  4 hours

• Determine the effect of KE on alcohol craving

  Compare the response to alcohol craving questionnaires after KE versus the Placebo drink

  4 hours

• Determine the effect of KE on brain reactivity to alcohol cues

  Compare Brain reactivity to alcohol cues as measured with functional MRI after KE versus the Placebo drink

  2 hours

Secondary Outcomes (2)

• Determine whether KE elevates brain ketone bodies using magnetic resonance spectroscopy

  2 hours

• Determine whether ghrelin levels in blood covary with alcohol craving and consumption

  4 hours

Study Arms (2)

Ketone ester with alcohol consumption

ACTIVE COMPARATOR

Drink a single dose of ketone ester 1.9 kcal/kg, complete 1 hour MRI scan, drink an alcohol priming dose to produce a 0.03 g/dl breath alcohol concentration (BrAC) followed by a choice paradigm in which subjects receive 2 trays of 4 min-drinks each beverages Each min-drink would achieve 0.015 g/ld BrAC over a 1 hour period to achieve a max 0.1 g/dl BrAC.

Dietary Supplement: Ketone Ester "(R)-3-hydroxybutyl (R)-3-hydroxybutyrate"; Other: Alcohol drinks

Isocaloric dextrose placebo drink with alcohol consumption

PLACEBO COMPARATOR

Drink a single dose of Isocaloric dextrose placebo drink, complete 1 hour MRI scan, drink an alcohol priming dose to produce a 0.03 g/dl breath alcohol concentration (BrAC) followed by a choice paradigm in which subjects receive 2 trays of 4 min-drinks each beverages Each min-drink would achieve 0.015 g/ld BrAC over a 1 hour period to achieve a max 0.1 g/dl BrAC.

Drug: Isocaloric dextrose placebo; Other: Alcohol drinks

Interventions

Ketone Ester "(R)-3-hydroxybutyl (R)-3-hydroxybutyrate" DIETARY_SUPPLEMENT

nutritional ketone ester

Also known as: Delta G

Ketone ester with alcohol consumption

Isocaloric dextrose placebo DRUG

Drink indistinguishable from ketone ester

Isocaloric dextrose placebo drink with alcohol consumption

Alcohol drinks OTHER

drink an alcohol priming dose to produce a 0.03 g/dl breath alcohol concentration (BrAC) followed by a choice paradigm in which subjects receive 2 trays of 4 min-drinks each beverages Each min-drink would achieve 0.015 g/ld BrAC over a 1 hour period to achieve a max 0.1 g/dl BrAC.

Isocaloric dextrose placebo drink with alcohol consumption; Ketone ester with alcohol consumption

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 21 years to 65 years old.
• Willingness to provide signed, informed consent and commit to completing the procedures in the study
• Meets DSM-5 criteria for AUD
• Average weekly ethanol consumption of at least 15 standard drinks over the past month prior to consent (self-report)
• Participants not seeking treatment for their AUD (self-report)
• Alcohol specified as the preferred drug (self-report).
• Women of child-bearing potential (i.e., who have not had a hysterectomy, bilateral oophorectomy, tubal ligation or is less than two years postmenopausal): must be non-lactating and practicing a reliable method of birth control, and have a negative urine pregnancy test prior to the initiation of the study and MRI procedures. Examples of medically acceptable methods for this protocol include: the birth control pill, intrauterine device (no copper IUD), injection of Depo-Provera, Norplant, contraceptive patch, contraceptive ring, double-barrier methods (such as condoms and diaphragm/spermicide), male partner sterilization, abstinence (and agreement to continue abstinence or to use an acceptable method of contraception, as listed above, should sexual activity commence), and tubal ligation.

You may not qualify if:

• Unwilling or unable to refrain from use, within 24 hours of MRI procedures, psychoactive medications or medication that may affect study results (e.g., analgesics containing narcotics, antibiotics, anti-inflammatory drugs).
• Current DSM-5 diagnosis of a major psychiatric disorder (other than alcohol and nicotine use disorders, or substance use disorders that are mild/moderate) that required hospitalization, or that required daily medications for over 4 weeks in the past year (i.e., antidepressants; anticholinergics; antipsychotics; anxiolytics; lithium; psychotropic drugs not otherwise specified (nos) including herbal products (no drugs with psychomotor effects or with anxiolytics, stimulant, antipsychotic, or sedative properties); sedatives/hypnotics).
• A current, clinically significant physical disease or abnormality on the basis of medical history, physical examination, or routine laboratory evaluation that can impact brain function, the use of a ketone ester or the use of alcohol (e.g., epilepsy, diabetes, liver disease, kidney disease, kidney stones, chronic metabolic acidosis or a cardiomyopathy as determined by history and clinical exam).
• Currently suffering from or with a history of stroke and/or stroke related spasticity.
• History of seizures.
• HIV positive, as the human immunodeficiency virus affects the brain.
• Head trauma with loss of consciousness for more than 30 minutes or associated with skull fracture or inter-cranial bleeding or abnormal MRI. (self-report, medical history).
• Presence of ferromagnetic objects in the body that are contraindicated for MRI of the head, fear of enclosed spaces, or other standard contraindication to MRI (self-report checklist).
• Claustrophobia or other medical condition preventing subject from lying comfortably flat on his/her back for up to 2 hours in the MRI scanner (self-report).
• BMI \> 35, body girth greater than 52 inches and a head girth greater than 25 inches (imaging data acquisition is impaired with high-weight individuals).
• Vision problems that cannot be corrected with glasses.
• Judged by the principal investigator or his designee to be an unsuitable candidate for study participation.

Sponsors & Collaborators

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

Study Sites (1)

University of Pennsylvania Center for Studies of Addiction

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

MeSH Terms

Conditions

Alcohol Drinking; Alcoholism

Interventions

Ethanol

Condition Hierarchy (Ancestors)

Drinking Behavior; Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Alcohols; Organic Chemicals

Study Officials

• Corinde E Wiers, Ph.D.

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Timothy S Pond, MPH

CONTACT

2152517736; timpond@pennmedicine.upenn.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Double blind
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: The study is a randomized, 2-way placebo-controlled crossover trial in 20 non-treatment seeking individuals with AUD.

Study Record Dates

• First Submitted: October 21, 2020
• First Posted: November 5, 2020
• Study Start: April 5, 2021
• Primary Completion (Estimated): December 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 9, 2026

Record last verified: 2026-02

Locations

US (1)