Using a ketone ester to reduce alcohol consumption in people with alcohol use disorder

Effects of Ketone Ester on Brain Function and Alcohol Consumption in Alcohol Use Disorder

This study is testing if a special drink made from ketones can help people with alcohol use disorder drink less by changing how their brains react to alcohol.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 21 Years to 65 Years
• Sex: All
• Sponsor: University of Pennsylvania (Academic / other)
• Locations: 1 site (Philadelphia, Pennsylvania)
• Trial ID: NCT04616781 on ClinicalTrials.gov

What this trial studies

This research investigates the effects of a nutritional ketone ester on brain function and alcohol consumption in individuals with alcohol use disorder (AUD). Participants will consume either the ketone ester or a placebo on separate testing days, followed by brain imaging and assessments of alcohol craving and consumption. The study aims to determine if the ketone ester can reduce brain reactivity to alcohol cues and cravings while elevating ketone bodies in the bloodstream. A total of 20 non-treatment seeking participants will undergo this double-blind, randomized, crossover design over a month.

Who should consider this trial

Good fit: Ideal candidates are adults aged 21 to 65 who meet the DSM-5 criteria for alcohol use disorder and consume at least 15 standard drinks per week.

Not a fit: Patients actively seeking treatment for their alcohol use disorder may not benefit from this study.

Why it matters

Potential benefit: If successful, this intervention could provide a novel approach to reducing alcohol cravings and consumption in individuals with alcohol use disorder.

How similar studies have performed: While previous studies have shown the potential of metabolic ketosis in reducing alcohol consumption in animal models, this specific approach in humans is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

1. Age 21 years to 65 years old.
2. Willingness to provide signed, informed consent and commit to completing the procedures in the study
3. Meets DSM-5 criteria for AUD
4. Average weekly ethanol consumption of at least 15 standard drinks over the past month prior to consent (self-report)
5. Participants not seeking treatment for their AUD (self-report)
6. Alcohol specified as the preferred drug (self-report).
7. 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.

Exclusion Criteria:

1. 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).
2. 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).
3. Urine drug screen positive for recent use of opioids, cocaine, or amphetamines on study visits (may be repeated once and if the result is negative on repeat it is not exclusionary).
4. 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).
5. Currently suffering from or with a history of stroke and/or stroke related spasticity.
6. History of seizures.
7. HIV positive, as the human immunodeficiency virus affects the brain.
8. 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).
9. 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).
10. 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).
11. 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).
12. Vision problems that cannot be corrected with glasses.
13. Judged by the principal investigator or his designee to be an unsuitable candidate for study participation.

Where this trial is running

Philadelphia, Pennsylvania

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

Study contacts

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

Conditions Alcohol Drinking; Alcohol Use Disorder; Ester Keytone; MRI