Effect of Nutritional Ketosis on Alcohol Metabolism (KAM)

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).

Study Overview

• Status: Recruiting
• Conditions: Alcohol Drinking; Magnetic Resonance Imaging; Ketoses, Metabolic; Ketogenic Dieting; Alcohol Intoxication
• Intervention / Treatment: Drug: Ethanol; Other: Control Diet; Dietary supplement: Ketone Supplement; Other: Ketogenic diet

Detailed 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 (Kenetik, Vitanav inc, Washington DC) 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.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 2; Phase 3

Contacts and Locations

• Study Contact: Name: Timothy S Pond, MPH; Phone Number: 215-746-1959; Email: timpond@upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania Center for Studies of Addiction
      • Sub-Investigator: Henry R. Kranzler, M.D.
      • Sub-Investigator: Kyle Kampman, M.D.
      • Contact: Timothy S. Pond, M.P.H.; Phone Number: 215-746-1959; Email: timpond@pennmedicine.upenn.edu
      • Principal Investigator: Corinde Wiers, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ketogenic diet; Eat a ketogenic diet for 3 days	Drug: Ethanol; After 3 days of diet intervention, participants will receive alcohol drinks that dose-adjusts for body weight and sex differences in pharmacokinetics and calculated to obtain a final breath alcohol concentration of 0.08%; Other Names: Alcohol
Placebo Comparator: Control Diet; Eat a control diet for 3 days	Drug: Ethanol; After 3 days of diet intervention, participants will receive alcohol drinks that dose-adjusts for body weight and sex differences in pharmacokinetics and calculated to obtain a final breath alcohol concentration of 0.08%; Other Names: Alcohol
Experimental: Ketone supplement; Eat a control diet for 3 days with a ketone supplement drink	Drug: Ethanol; After 3 days of diet intervention, participants will receive alcohol drinks that dose-adjusts for body weight and sex differences in pharmacokinetics and calculated to obtain a final breath alcohol concentration of 0.08%; Other Names: Alcohol; Other: Control Diet; Control Diet breakfast, lunch, and dinner for 3 days.; Other Names: ~ 50% kcal carbohydrates diet
Experimental: Alcohol Intervention; 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%	Other: Control Diet; Control Diet breakfast, lunch, and dinner for 3 days.; Other Names: ~ 50% kcal carbohydrates diet; Dietary supplement: Ketone Supplement; Ketone supplement 3x day with control diet for 3 days.; Other Names: D-Beta-hydroxybutyric acid and R-1,3 butanediol; Other: Ketogenic diet; Ketogenic Diet breakfast, lunch, and dinner for 3 days.; Other Names: ~5-10% kcal carbohydrates diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in breath alcohol concentration	Breath alcohol concentration measured in mg/L of air. The range is .000 to .400 g/L. Change in breath alcohol concentration, pre to post alcohol consumption after 3 day diet intervention during lab day.	3 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in motor agility tasks	Motor agility will be assessed with the grooved pegboard task, in which participants will place pegs onto a metal surface containing 25 keyhole-shaped holes that differ in orientation. Measured in seconds, range 0 to 5 minutes. Change in motor agility tasks pre to post alcohol consumption after 3 day diet intervention.	3 hours
Change in cognitive performance tasks	Cognitive performance will be measured with a cued go/no-go task, in which participants will press a computer keyboard key in response to a "go" target and suppress the action in response to a "no-go" target. Measured in % correct responses 0-100. Pre to post alcohol consumption after 3 day diet intervention.	3 hours

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Study Director: Kyle Kampman, MD, University of Pennsylvania; Principal Investigator: Corinde Wiers, Ph.D., University of Pennsylvania; Study Director: Henry Kranzler, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): January 18, 2023
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: September 20, 2023
• First Submitted That Met QC Criteria: September 29, 2023
• First Posted (Actual): October 4, 2023

Study Record Updates

• Last Update Posted (Actual): January 24, 2024
• Last Update Submitted That Met QC Criteria: January 22, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Ketone supplement
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Metabolic Diseases; Drinking Behavior; Alcohol-Related Disorders; Substance-Related Disorders; Acid-Base Imbalance; Acidosis; Alcohol Drinking; Ketosis; Alcoholic Intoxication; Physiological Effects of Drugs; Anti-Infective Agents, Local; Anti-Infective Agents; Central Nervous System Depressants; Ethanol
• Other Study ID Numbers: 853707; 24446 (Other Grant/Funding Number: UPenn ITMAT)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No