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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore how a ketone supplement affects symptoms during alcohol withdrawal compared to a placebo. Researchers seek to determine if the supplement can ease withdrawal in adults with moderate to severe alcohol use disorder. Participants will receive either the ketone supplement (known as Ketone Ester, DeltaG, or D-β-hydroxybutyric acid and R-1,3-butanediol) or a look-alike placebo drink over a 4-day treatment period. This trial may suit those who have had a heavy drinking habit for at least three years and are currently experiencing alcohol withdrawal symptoms. As a Phase 2, Phase 3 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment advancements.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that ketone supplements are usually safe for use. In one study lasting 28 days with 59 healthy adults, a specific type of ketone supplement proved safe and did not cause major side effects. Another study found that daily use of a ketone ester was safe for older adults. These findings suggest that ketone supplements generally do not cause serious issues for most people. However, individual differences exist, so consulting a healthcare provider before joining a trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for alcohol withdrawal?

Unlike the standard treatments for alcohol withdrawal, such as benzodiazepines and anticonvulsants, the ketone supplement in this study uses D-beta-hydroxybutyric acid and R-1,3 butanediol to potentially ease withdrawal symptoms. Researchers are excited about this treatment because it targets the brain's energy metabolism, offering a novel approach compared to traditional methods that focus on calming the nervous system. Additionally, the supplement is administered orally and could work more rapidly, showing effects in just a few days. This unique mechanism and potentially faster action make it a promising alternative to current options.

What evidence suggests that this treatment might be an effective treatment for alcohol withdrawal?

Studies have shown that ketone supplements can help reduce alcohol cravings, lower alcohol consumption, and ease withdrawal symptoms. In this trial, participants will receive either the ketone supplement or a placebo beverage. Research suggests these supplements provide the brain with a different energy source, which might help with withdrawal. Users of ketone supplements reported fewer cravings and drank less alcohol. This suggests that ketone supplements could effectively manage alcohol withdrawal symptoms. ^{4 5 6 7 8}

Who Is on the Research Team?

Corinde Wiers, Ph.D.

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

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

I experience intense fear in enclosed spaces.

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

Group I: Ketone Supplement Experimental Treatment 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+

Published Research Related to This Trial

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10901540/

Ketone Supplementation Dampens Subjective and ... A high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38315678/

Evidence From a Preclinical Rat Study and a Randomized ... A high-fat ketogenic diet and ketone supplements (KS) are efficacious in reducing alcohol craving, alcohol consumption, and signs of alcohol withdrawal.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06173973

Effects of Ketone Supplementation on Acute Alcohol ... Participants will be consented and randomized to receive 10 g of ketone supplement three times daily (n=30; 1,3-butanediol and D-hydroxybutyric acid from ...

4. sciencedirect.com sciencedirect.com/science/article/pii/S1279770724004160

Daily consumption of ketone ester, bis-octanoyl (R) In conclusion this pilot study demonstrated the safety and tolerability of 12-weeks of consumption of up to 25 g per day of the ketone di-ester, bis-octanoyl (R)- ...

5. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1195702/full

An open-label, acute clinical trial in adults to assess ketone ... In this study, the administration of a single serving of 10 g of (R)-1,3-butanediol resulted in a peak blood BHB level of 1.2 mmol/L at 39 min, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12329427/

Ketone Supplements and Alcohol‐Related Responses in ... Although preclinical studies have revealed that a ketogenic diet or a mix of ketone supplements reduces alcohol intake and alleviates withdrawal ...

7. withpower.com withpower.com/trial/phase-2-and-3-alcohol-drinking-9-2022-520b4

Ketone Supplement for Alcohol Consumption Effects In a 28-day study involving 59 healthy adults, the novel exogenous ketone diester bis-hexanoyl-(R)-1,3-butanediol (BH-BD) was found to be well-tolerated and ...

8. mdpi.com mdpi.com/1424-8247/18/10/1436

Divergent Hepatic Outcomes of Chronic Ketone ... This study evaluated the formulation-dependent impact of chronic ketone supplementation on liver histopathology, inflammatory signaling, and systemic biomarkers ...