Ketone Ester for Alcoholism

Overseen By Juliana Byanyima, BS

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: University of Pennsylvania

Must not be taking: Antidepressants, Antipsychotics, Anxiolytics, others

Disqualifiers: Pregnancy, Major psychiatric disorder, Stroke, Seizures, HIV, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

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

Compensation: Varies

Number of Visits: 5

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores how a nutritional supplement called ketone ester affects brain and heart function, as well as alcohol consumption. Researchers will use special scans (PET/CT scans) to observe changes after a single dose of ketone ester or a placebo. The trial involves two groups: one with individuals who have alcohol use disorder (AUD) and another with healthy participants. Those with AUD should have a history of heavy drinking, while healthy volunteers should drink moderately. This study could provide insights into how ketone ester might help reduce alcohol consumption. As a Phase 2 trial, this research measures how well ketone ester works in an initial, smaller group, offering participants a chance to contribute to potential advancements in treatment.

Will I have to stop taking my current medications?

The trial requires participants to refrain from using psychoactive medications or any medication that may affect study results within 24 hours of the PET/CT scan. This includes medications like narcotics, antibiotics, and anti-inflammatory drugs.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Previous studies have shown that the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is safe. This dietary supplement can quickly raise blood ketone levels. Research with 24 healthy adults found that this ketone ester was well-tolerated, with no major side effects reported. Its availability for purchase further suggests its well-established safety. Overall, evidence indicates that the ketone ester is a safe option for those considering joining this trial. ^{1 2 3 4 5}

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

Unlike the standard treatments for alcoholism, which often include medications like naltrexone or acamprosate, this investigational treatment uses a ketone ester, specifically (R)-3-hydroxybutyl (R)-3-hydroxybutyrate. Researchers are excited about this because ketone esters might offer a novel way to influence brain energy metabolism, potentially reducing cravings and withdrawal symptoms. This approach could be a game-changer, as it targets the brain's energy supply rather than just neurotransmitter systems, providing a fresh angle in the fight against alcohol dependency.

What evidence suggests that ketone ester might be an effective treatment for alcoholism?

Research has shown that a substance called ketone ester might help reduce alcohol consumption. Specifically, the type of ketone ester studied is (R)-3-hydroxybutyl (R)-3-hydroxybutyrate. In this trial, some participants will receive a single dose of ketone ester during an echocardiogram and PET FDG scanning visit. Studies suggest that ketone ester can influence brain function, potentially managing alcohol cravings or reducing drinking. Some research also indicates that ketone esters could lessen anxiety during alcohol withdrawal, which may benefit early recovery stages. Additionally, ketone ester is considered safe and has been tested as a dietary supplement. These findings suggest it might be helpful for individuals with alcohol use disorder. ^{1 2 5 6 7}

Who Is on the Research Team?

Corinde E Wiers, Ph.D.

Principal Investigator

University of Pennsylvania

Are You a Good Fit for This Trial?

This trial is for adults aged 21-65, with or without alcohol use disorder, who can commit to the study and avoid alcohol for 24 hours before sessions. Excluded are those with seizures, high BMI (>35), metal implants incompatible with MRI/PET scans, vision issues not corrected by glasses, serious medical/psychological conditions, HIV positive individuals, pregnant/breastfeeding women, and certain psychiatric diagnoses.

Inclusion Criteria

Alcohol specified as the preferred drug (self-report) (for AUD group)

Participants must agree to not consume alcohol beverages for 24 hours prior to each laboratory session

AUDIT score < 6 (for control group)

Exclusion Criteria

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) or PET scanner

Positive urine drug screen positive for any substances, other than marijuana, on study visits (may be repeated once and if the result is negative on repeat it is not exclusionary)

I've had a severe head injury with loss of consciousness, skull fracture, or bleeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2 weeks

1 visit (in-person or virtual)

MRI Scan

Participants undergo an MRI scan to assess brain anatomy and function

1 hour

1 visit (in-person)

PET/CT Scan with Ketone Ester

Participants receive a ketone ester drink and undergo a PET/CT scan to assess brain and heart function

3-4 hours

1 visit (in-person)

PET/CT Scan without Ketone Ester

Participants undergo a PET/CT scan without the ketone ester to assess baseline brain and heart function

3-4 hours

1 visit (in-person)

Follow-up

Participants are monitored for any side effects and changes in health after the study visits

1 day

1 follow-up call

What Are the Treatments Tested in This Trial?

Interventions

• FDG
• Ketone Ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate)

Trial Overview The study tests how a nutritional supplement 'ketone ester' affects brain and heart function and alcohol consumption in people with alcohol use disorder compared to healthy volunteers. It involves taking a single dose of ketone ester or placebo followed by PET/CT scans using FDG.

How Is the Trial Designed?

Group I: Echocardiogram + PET FDG scanning visit. Experimental Treatment 1 Intervention

Subjects will complete a echocardiogram + PET scanning visit. 2-Deoxy-2-\[18F\] fluoro-D-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) scan.

Group II: Ketone ester + echocardiogram + PET FDG scanning visit. Active Control 2 Interventions

Subjects will drink single dose of ketone ester 1.9 kcal/kg + echocardiogram + PET scanning visit. Dietary Supplement: Ketone Ester "(R)-3-hydroxybutyl (R)-3-hydroxybutyrate" (R)-3-hydroxybutyrate (commercially available as DeltaG, (TdeltaS, Orlando, FL). 2-Deoxy-2-\[18F\] fluoro-D-glucose (FDG) Positron Emission Tomography/Computed Tomography (PET/CT) scan.

Who Is Running the Clinical Trial?

University of Pennsylvania

Lead Sponsor

Trials

2,118

Recruited

45,270,000+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT04616781

Ketone Ester Intervention in Alcohol Use Disorder The purpose of this research is to study how a nutritional ketone ester may effect brain function and alcohol consumption in regular alcohol users.

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8670944/

Nutritional Ketosis as a Potential Treatment for Alcohol Use ... The nutritional supplement (R)-3-hydroxybutyl (R)-3-hydroxybutyrate (Ketone Ester; KE) is a safe (13, 33), effective, and commercially available method ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05015881?tab=history&a=6

Record History | ver. 6: 2024-07-29 | NCT05015881 The goal of this study is to learn more about how a nutritional supplement "ketone ester" (deltaG ®) has an effect on brain and heart function and on alcohol ...

4. trialfinder.panfoundation.org trialfinder.panfoundation.org/en-US/trial/listing/387124

Ketone Ester Intervention in Alcohol Use Disorder Primary outcome measures. Determine the effects of ketone ester "R)-3-hydroxybutyl (R)-3-hydroxybutyrate" (KE) on alcohol consumption (4 hours).

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7914216/

Effects of ketogenic diet and ketone monoester supplement on ... The regular diet with ketone monoester was sufficient to reduce handling-induced convulsions and anxiety-like behaviors in early withdrawal.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC3810007/

Kinetics, safety and tolerability of (R)-3-hydroxybutyl (R) These results suggest ingestion of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate is a safe and simple method to elevate blood ketone levels.

7. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0273230019302703

Safety and tolerability of sustained exogenous ketosis ... Here we report results for 24 healthy adults, aged 18–70 years, who drank 25 ml (26.8 g) of the ketone monoester, (R)-3-hydroxybutyl (R)-3-hydroxybutyrate, ...