Ketone Supplement for Alcohol Withdrawal

(KSAW Trial)

Overseen By Timothy Pond, MPH

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Pennsylvania

Must not be taking: Benzodiazepines, Opioids

Disqualifiers: Major psychiatric disorder, Epilepsy, Diabetes, HIV, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 2

Duration: 4 days

30 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are experiencing significant withdrawal from substances like benzodiazepines or opioids, you may not be eligible to participate.

What data supports the effectiveness of the ketone supplement treatment for alcohol withdrawal?

Research shows that ketone supplements can reduce alcohol craving, consumption, and withdrawal symptoms. Studies in humans and animals found that ketone supplements lowered alcohol levels in the body and reduced the desire for alcohol, suggesting they could help manage alcohol use disorder. ^{1 2 3 4 5}

Is ketone supplementation safe for humans?

Research shows that ketone supplements, like D-β-hydroxybutyric acid and R-1,3-butanediol, have been used in studies with humans and rats to reduce alcohol withdrawal symptoms and cravings. These studies did not report any major safety concerns, suggesting that ketone supplements are generally safe for human use. ^{1 2 4 5 6}

How is the ketone supplement treatment different from other treatments for alcohol withdrawal?

The ketone supplement treatment is unique because it uses ketone bodies as an alternative energy source for the brain, which may help reduce alcohol withdrawal symptoms by compensating for the energy deficit caused by a drop in acetate levels during withdrawal. This approach is different from traditional treatments that often focus on managing symptoms with medications like benzodiazepines. ^{1 2 3 5 6}

Research Team

Corinde Wiers, Ph.D.

Principal Investigator

University of Pennsylvania

Eligibility Criteria

This trial is for adults with moderate to severe alcohol use disorder who are undergoing a 4-day alcohol withdrawal treatment. It's being conducted at the Hospital of the University of Pennsylvania, Cedar Detox Center.

Inclusion Criteria

Minimum 3-year history of heavy drinking (self-report)

Able to communicate in English and provide written informed consent

Presence of alcohol withdrawal (DSM-5)

Exclusion Criteria

Pregnant or breast-feeding

BMI greater than 35

Contraindications to MRI (e.g., metal in the body that cannot be removed)

Timeline

Screening

Participants are screened for eligibility to participate in the trial

1 day

1 visit (in-person)

Treatment

Participants receive either ketone supplement or placebo beverage for alcohol withdrawal management

4 days

Daily visits (in-person)

Follow-up

Participants undergo a magnetic resonance imaging session to assess brain metabolism

1 day

1 visit (in-person)

Treatment Details

Interventions

• Ketone Supplement

Trial Overview The study is testing if a ketone supplement can help with alcohol withdrawal symptoms compared to a placebo. Participants will also undergo an MRI session to see how their brain metabolism might be affected.

Participant Groups

Group I: Ketone Supplement Active Control 2 Interventions

Ketone supplement "D-beta-hydroxybutryric acid and R-1,3 butanediol" (Kenetik: Ketone Drink, VitaNav Inc., Washington D.C.) 12g of ketones, three times a day before meals, by mouth for 4 days plus 1 dose on day 5 for magnetic resonance imaging session visit.

Group II: Placebo Beverage Placebo Group 2 Interventions

Placebo beverage, visually matched, three times a day before meals, by mouth for 4 days plus 1 dose on day 5 for magnetic resonance imaging session visit.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

National Institute on Alcohol Abuse and Alcoholism (NIAAA)

Collaborator

Trials

865

Recruited

1,091,000+

Findings from Research

In a study with 10 healthy participants, ketone supplements (KS) significantly reduced breath alcohol concentration (BrAC) and blood alcohol levels (BAL) after alcohol consumption, indicating a potential to lessen the intoxicating effects of alcohol.

In a parallel study with rats, KS also lowered BAL more effectively than water or a sweetener, suggesting that ketones may alter both physiological and subjective responses to alcohol, making them a promising intervention for alcohol use disorder.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketone supplementation dampens subjective and objective responses to alcohol in rats and humans. Li, X., Shi, Z., Todaro, D., et al.[2023]

In a study involving 33 inpatients with alcohol use disorder, those on a ketogenic diet (KD) required fewer benzodiazepines during detoxification compared to those on a standard American diet, suggesting that KD may help reduce withdrawal severity.

The KD not only altered brain metabolism by increasing ketones and glutamate while lowering neuroinflammatory markers but also showed potential in reducing alcohol cravings and consumption, as evidenced by a rat model of alcohol dependence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents. Wiers, CE., Vendruscolo, LF., van der Veen, JW., et al.[2022]

Nutritional ketosis, achieved through a ketogenic diet or ketone ester ingestion, may help reduce withdrawal symptoms and cravings in individuals with alcohol use disorder (AUD), based on both preclinical and clinical studies.

The mechanism behind this effect involves a shift in metabolism from glucose to acetate during alcohol intoxication, and a decline in acetate levels during withdrawal, which nutritional ketosis can help counteract.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder. Mahajan, VR., Elvig, SK., Vendruscolo, LF., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Ketone supplementation dampens subjective and objective responses to alcohol in rats and humans. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Ketogenic diet reduces alcohol withdrawal symptoms in humans and alcohol intake in rodents. [2022]

3. Germany pubmed.ncbi.nlm.nih.gov

Effects of ketogenic diet and ketone monoester supplement on acute alcohol withdrawal symptoms in male mice. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Ketogenic diet reduces a neurobiological craving signature in alcohol use disorder. [2023]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Nutritional Ketosis as a Potential Treatment for Alcohol Use Disorder. [2022]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Suppression of an ethanol withdrawal syndrome in rats by butyrate, lactate and beta-hydroxybutyrate. [2019]