Ketone Esters for Fatty Liver Disease

(JV Trial)

Overseen By Nikki Plassmeyer, RDN, LD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 2

Sponsor: Washington University School of Medicine

Must not be taking: Corticosteroids, others

Disqualifiers: Diabetes, Eating disorders, Liver disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 6 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if a daily ketone ester drink can improve liver health and blood sugar control in individuals with fatty liver disease. Participants will be randomly assigned to consume either the ketone ester (bis-octanoyl (R)-1,3-butanediol, also known as C8 ketone di-ester) or a placebo for six weeks. The trial seeks individuals with a BMI over 30 who have been diagnosed with fatty liver disease and do not have other complicating conditions. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Do I have to stop taking my current medications for the trial?

You may need to stop taking certain medications that affect the study outcomes, like corticosteroids, but you can continue taking metformin if you've been on a stable dose for at least 3 months without any stomach issues. The trial protocol doesn't specify other medications, so it's best to discuss your current medications with the study team.

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

Research has shown that daily consumption of a C8 ketone di-ester, a type of ketone drink, is generally safe and well-tolerated by healthy older adults. In one study, participants who consumed this ketone drink reported no serious side effects, suggesting its safety for use. However, individual responses can vary, so monitoring for any negative effects during the trial is important. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for fatty liver disease?

Unlike the standard treatments for fatty liver disease, which often involve lifestyle changes and medications like vitamin E or pioglitazone, the C8 ketone di-ester offers a novel approach. This treatment is unique because it introduces a new active ingredient, bis-octanoyl (R)-1,3-butanediol, which is a ketone ester. Ketone esters can provide an alternative energy source for the liver, potentially reducing liver fat more effectively. Researchers are excited because this treatment targets the condition in a totally different way, offering hope for quicker and possibly more profound improvements.

What evidence suggests that this treatment might be an effective treatment for fatty liver disease?

Research has shown that ketone esters, such as bis-octanoyl (R)-1,3-butanediol, might help reduce liver fat and improve liver health. The liver naturally produces ketones when the body burns fat, especially during fasting or low-carb diets. One study found that this ketone ester raised ketone levels in the body, potentially decreasing liver fat. Another study discovered that ketone esters could improve nonalcoholic fatty liver disease by reducing liver fat and enhancing liver function. In this trial, participants will receive either the C8 ketone di-ester or a placebo to evaluate its potential benefits in treating fatty liver disease. ^{1 2 4 6 7}

Who Is on the Research Team?

Samuel Klein, MD

Principal Investigator

Washington University School of Medicine

Are You a Good Fit for This Trial?

This trial is for individuals with fatty liver disease, a history of stroke, or obesity. Participants will be randomly assigned to consume either a ketone ester drink or a placebo daily for 6 weeks.

Inclusion Criteria

I am between 18 and 22 years old.

Intrahepatic triglyceride content >5% assessed by using magnetic resonance imaging-proton density fat fraction (MRI-PDFF)

BMI: 30.0 - 44.9 kg/m2

Exclusion Criteria

Unable or unwilling to follow study protocol or considered inappropriate candidate by research team

Fibroscan controlled attenuation parameter (CAP) score <240 dB/m assessed within last 2 months before study entry

Unwilling or unable to provide informed consent

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomly assigned to consume either a ketone ester drink or a placebo drink daily for 6 weeks

6 weeks

Visits at the start and end of treatment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester)

Trial Overview The study aims to see if drinking bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester) can improve liver health and blood glucose control compared to a placebo in people with certain metabolic conditions.

How Is the Trial Designed?

Group I: C8 ketone di-ester Experimental Treatment 1 Intervention

25 g C8 ketone di-ester per day for approximately 6-weeks

Group II: Placebo Placebo Group 1 Intervention

25 g Placebo per day for approximately 6-weeks

Who Is Running the Clinical Trial?

Washington University School of Medicine

Lead Sponsor

Trials

2,027

Recruited

2,353,000+

Children's Discovery Institute

Collaborator

Trials

6

Recruited

540+

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT07097506

Effect of Ketone Esters on Liver Fat Content and Metabolic ... Ketones are produced by the liver from fatty acid metabolism; increased ketone production is observed during fasting or very-low carbohydrate (ketogenic) ...

2. trialx.com trialx.com/clinical-trials/listings/310491/effect-of-ketone-esters-on-liver-fat-content-and-metabolic-function/

Effect of Ketone Esters on Liver Fat Content and Metabolic ... Ketones are produced by the liver from fatty acid metabolism; increased ketone production is observed during fasting or very-low carbohydrate (ketogenic) diet ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11065008/

1,3-butanediol, and its acute effect on ß-hydroxybutyrate ... Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel fatty-acid ketone ester that robustly stimulates hepatic ketone production, independently of dietary ...

4. frontiersin.org frontiersin.org/journals/physiology/articles/10.3389/fphys.2023.1165224/full

Dietary ketone ester attenuates the accretion of adiposity ... ... hepatic steatosis and hepatic mitochondrial metabolism in nonalcoholic fatty liver disease. ... outcomes of NAFLD and markers of fibrosis in high-fat diet ...

5. withpower.com withpower.com/trial/phase-2-masld---metabolic-dysfunction-associated-steatotic-liver-disease-8-2025-411fa

Ketone Esters for Fatty Liver Disease (JV Trial) ... bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester) will have tolerable side effects & efficacy for patients with Obesity, Fatty Liver Disease and Obesity. See

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11695072/

Daily consumption of ketone ester, bis-octanoyl (R) Daily consumption of ketone ester, bis-octanoyl (R)-1,3-butanediol, is safe and tolerable in healthy older adults in a randomized, parallel arm, double-blind, ...

7. medrxiv.org medrxiv.org/content/10.1101/2024.04.16.24305925v1

1,3-butanediol, and its acute effect on ß-hydroxybutyrate ... Bis-octanoyl (R)-1,3-butanediol (BO-BD) is a novel ketone ester (KE) ingredient which increases blood beta-hydroxybutyrate (BHB) concentrations ...