Effect of Nutritional Ketosis on Alcohol Metabolism (KAM)

University of Pennsylvania

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Ketoses, Metabolic; Alcohol Intoxication; Ketogenic Dieting; Alcohol Drinking; Magnetic Resonance Imaging

Treatments: Drug: Ethanol; Dietary Supplement: Ketone Supplement; Other: Control Diet; Other: Ketogenic diet

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT06065657

R21AA031088-01A1 (U.S. NIH Grant/Contract)

853707

24446 (Other Grant/Funding Number)

Details and patient eligibility

About

The research study is being conducted in health controls to better understand the effects of ketosis on brain functioning after 3 different, randomly assigned, 3-day dietary interventions and the acute effects of alcohol after consuming about 4-5 alcohol beverages. The labs visits will use magnetic resonance imaging (MRI) scans to study the brain, measuring levels of nicotinamide adenine dinucleotide (NAD), lactate, neurotransmitters glutamate, and Gamma-aminobutyric acid (GABA).

Full description

The research study is being conducted to better understand the effects of ketosis on brain functioning and the acute effects of alcohol. Healthy participants will undergo three randomly assigned dietary interventions, each lasting three days, followed by a study lab visit day on day 4. The three interventions are: (1) Eat a ketogenic diet for 3 days, (2) eat a control diet for 3 days with a ketone supplement drink, and (3) eat a control diet for 3 days. The dietary interventions will be spaced 1 week apart. The ketone supplement drink "bis-octanoyl (R)-1,3-butanediol" (Kenetik: Ketone Drink, VitaNav Inc., Washington D.C.) 12.5g of ketones, TID PO (by mouth).) is a dietary supplement that has been extensively studied in humans and is designated by the FDA as Generally Recognized as Safe (GRAS). Its use in this study is experimental. On the day of the 3 labs visits days, magnetic resonance imaging (MRI) will be used to study the brain. Specifically, levels of nicotinamide adenine dinucleotide (NAD) (a coenzyme that is important for energy metabolism), lactate (a metabolite produced during energy metabolism), and neurotransmitters glutamate and GABA. Following the scans, participants will be provided a dose of alcohol that will elevate participants breath alcohol levels to approximately 0.08% to measure the acute effects of alcohol.

Enrollment: 20 estimated patients

Sex: All

Ages: 21 to 50 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

1. Willingness to provide signed, informed consent and commit to completing study procedures.
2. Reported on at least one day in the month prior to consent of consuming 2 or more standard alcohol drinks on a single day.

Exclusion criteria

1. Unwilling or unable to refrain from use, within 24 hours of the alcohol lab procedures, psychoactive medications or medication that may affect study results.
2. Current Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) diagnosis of any major psychiatric disorder (other than nicotine use disorders, or marijuana use disorders) as identified by clinical examination or structured interview that could interfere with study participation or make it hazardous for the subject.
3. Currently taking medication(s) that could interfere with study participation or make it hazardous for the subject to participate. (e.g. anticholinergics; antipsychotics; lithium; psychotropic drugs not otherwise specified)
4. Positive urine drug screen, positive for all substances but marijuana at screening or study visits (may be repeated once and if the result is negative on repeat, it is not exclusionary).
5. A current, clinically significant physical disease or abnormality on the basis of medical history, or routine laboratory evaluation that can impact brain function, the use of a ketone supplement, administration of ketogenic diet, or the use of alcohol (e.g., epilepsy, diabetes, irritable bowel syndrome, Crohn's disease, liver disease, kidney disease, kidney stones, chronic metabolic acidosis or a cardiomyopathy as determined by history and clinical exam).
6. Currently suffering from or has a history of stroke and/or stroke related spasticity.
7. Head trauma with loss of consciousness for more than 30 minutes or associated with skull fracture, inter-cranial bleeding or abnormal MRI (self-report, medical history).
8. Weight greater than 225lbs (Need to cap amount of alcohol given based on weight to individuals).
9. Females who are pregnant or breast-feeding
10. Contraindication to MRI, including presence of ferromagnetic objects, claustrophobia or fear of enclosed, medical conditions that prevent subjects from lying comfortably flat on his/ her back for up to 2 hrs.

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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20 participants in 4 patient groups, including a placebo group

Ketogenic diet

Experimental group

Description:

Eat a ketogenic diet for 3 days

Treatment:

Drug: Ethanol

Control Diet

Placebo Comparator group

Description:

Eat a control diet for 3 days

Treatment:

Drug: Ethanol

Ketone supplement

Experimental group

Description:

Eat a control diet for 3 days with a ketone supplement drink

Treatment:

Other: Control Diet

Drug: Ethanol

Alcohol Intervention

Experimental group

Description:

Alcohol lab, participants will receive ethanol drinks that are dose-adjusted for body weight and sex differences in pharmacokinetics and calculated to obtain a final breath alcohol concentration of 0.08%

Treatment:

Other: Ketogenic diet

Other: Control Diet

Dietary Supplement: Ketone Supplement