MASLD - Metabolic Dysfunction-Associated Steatotic Liver DiseasePhase 2JVNCT07097506
Effect of Ketone Esters on Liver Fat Content and Metabolic Function
A Phase 2 study testing bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester) in people with MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease and Obesity, run by Washington University School of Medicine at 1 site in United States.
Trial summary
The goal of this clinical trial is to determine whether ingestion of a ketone ester drink helps improve liver health and blood glucose control. Ketones are a type of energy source made by the body during times of weight loss, low carbohydrate intake and starvation. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, Obesity, Overweight (BMI > 25)
- What is being tested?
- bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited States
- Study dates
- 26 Sep 2025to 31 Dec 2027
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Age: ≥18 and ≤40 years;
- BMI 25.0 - 49.9 kg/m2;
- Intrahepatic triglyceride content >5% assessed by using magnetic resonance imaging-proton density fat fraction (MRI-PDFF).
Who cannot join
- HbA1C ≥6.5%;
- taking dietary supplements or medications known to affect our study outcomes including corticosteroids and other drugs associated with steatosis (metformin use will be allowable if participants have taken a stable dose for at least 3 months without any gastrointestinal-related symptoms);
- active eating disorder, any anaphylactic food allergy and/or consuming a very-low-carbohydrate (<50 g/day) diet;
- Fibroscan controlled attenuation parameter (CAP) score <240 dB/m assessed within last 2 months before entering the study;
- recent (<2 months) history of moderate-severe nausea, vomiting, diarrhea, or other significant gastrointestinal symptoms;
- consume tobacco products, excessive alcohol (females: >14 drinks/week; males: >21 drinks/week), or illegal drugs determined by medical history;
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- evidence of significant active organ system dysfunction, liver disease other than MASLD (e.g., Wilson disease, viral hepatitis, inborn errors of metabolism, or alpha-1 antitrypsin deficiency) or cirrhosis as a results of any condition or disease;
- have had bariatric surgery or plan to have endoscopic or bariatric surgery therapy for obesity;
- have undergone organ transplantation;
- have HIV and any other type of congenital or acquired lipodystrophy;
- unwilling or unable to provide informed consent;
- major psychiatric illness;
- metal implants that are not MRI-compatible;
- pregnancy, as determined by a urine HCG screening test assessed performed at all screening, baseline testing, and follow-up visits. In addition, male and female participants of reproductive and childbearing age who wish to enroll will be required to agree to use contraception throughout the study period, and for 30 days after the last dose of C8 ketone di-ester;
- female participants who are currently lactating;
- Structured exercise: ≥75 min/wk of vigorous exercise (e.g., jogging, activity that causes heavy breathing and sweating) or ≥200 min/wk of low intensity physical activity (e.g., brisk walking);
- Unstable weight (>3% change during the last 2 months before entering the study);
- Anemia (hemoglobin <10.5 g/dL in females and <11.0 g/dL in males);
- Unable or unwilling to follow the study protocol or who, for any reason, is considered an inappropriate candidate for the study by the research team.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Washington University School of Medicine
St Louis, Missouri, 63110
Nikki Plassmeyer, RDN, LD, 314-362-0590, nikkip@wustl.edu
Central contact information, 314-273-1879, nutritionresearch@wustl.edu
About this study
Official title: Effect of Ketone Esters on Liver Fat and Metabolic Function in Adolescents and Young Adults With Overweight/Obesity and MASLD
The goal of this clinical trial is to determine whether ingestion of a ketone ester drink helps improve liver health and blood glucose control. Ketones are a type of energy source made by the body during times of weight loss, low carbohydrate intake and starvation.
People enrolled in this study will be randomly assigned (by chance, like the flip of a coin) to one of two groups:
Group 1: Ketone ester drink consumed daily for 6 weeks. Group 2: Placebo drink consumed daily for 6 weeks.
Read the detailed description
Metabolic dysfunction-associated steatotic liver disease (MASLD) is a common complication of obesity and is associated with multiorgan insulin resistance, dyslipidemia (high plasma triglyceride and low HDL cholesterol concentrations), and an increased risk of diabetes and coronary heart disease. The prevalence of MASLD continues to rise dramatically in children and adolescents, with approximately 13 to 19% of adolescents and young adults in the United States estimated to have hepatic steatosis (elevated amount of fat in the liver), the hallmark feature of MASLD. Evidence is emerging that increasing blood ketone concentrations can markedly improve hepatic steatosis, insulin sensitivity, and blood glucose in rodent models of obesity.
Ketones are produced by the liver from fatty acid metabolism; increased ketone production is observed during fasting or very-low carbohydrate (ketogenic) diet consumption when plasma nonesterified fatty acid concentrations are high and glucose concentrations are low. Circulating ketone concentrations can also be increased by exogenous ketone administration. Ketogenic diets ameliorate hepatic steatosis in adults with MASLD. Whether exogenous ketone administration affects hepatic steatosis in adolescents and young adults with MASLD is not known. However, several studies have found exogenous ketone administration improves blood glucose control in people, suggesting that exogenous ketones could also reduce intrahepatic triglyceride (IHTG) content.
The therapeutic use of ketone drinks has been limited by poor palatability and the high sodium content of ketone salts. To overcome these limitations, ketone esters have recently been developed, including bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester), which is hydrolyzed in the intestine to generate the ketone precursors octanoic acid and (R)-1,3-butanediol, which are then converted to beta-hydroxybutyrate by the liver. These ketone precursors are palatable, do not contain sodium, and have been shown to increase plasma ketone concentrations. The purpose of the present study is to conduct a randomized double blind, placebo-controlled 6-week trial to assess the effect of C8 ketone di-ester supplementation (25 g/day) on IHTG content and blood glucose control (insulin sensitivity, beta-cell function, glucose tolerance) in 40 adolescents and young adults with overweigh/obesity and MASLD.
- Conditions
- MASLD - Metabolic Dysfunction-Associated Steatotic Liver Disease, Obesity, Overweight (BMI > 25)
- Being tested
- bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester), Placebo
- Medical subject headings
- Obesity, Overweight
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester)Drug
Also called Qitone
25 g C8 ketone di-ester taken daily for approximately 6-weeks
PlaceboOther
25 g Placebo taken daily for approximately 6-weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | 25 g Placebo per day for approximately 6-weeks Receives: Other: Placebo |
| C8 ketone di-ester | Experimental | 25 g C8 ketone di-ester per day for approximately 6-weeks Receives: Drug: bis-octanoyl (R)-1,3-butanediol (C8 ketone di-ester) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Intrahepatic triglyceride content
Intrahepatic triglyceride content will be assessed by magnetic resonance imagining (MRI)
Measured: Before and at the end of treatment at 6-weeks
Change in insulin sensitivity
Whole-body insulin sensitivity will be assessed by using the hyperinsulinemic-euglycemic clamp procedure
Measured: Before and at the end of treatment at 6-weeks
Secondary outcomes (2)
Change in β-cell function
β-cell function will be assessed from a modified oral glucose tolerance test
Measured: Before and at the end of treatment at 6-weeks
Change in glycemic control
Glycemic control will be assessed by using an oral glucose tolerance test
Measured: Before and at the end of treatment at 6-weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jul 2025
- Study start26 Sep 2025
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MASLD - Metabolic Dysfunction-Associated Steatotic Liver DiseaseStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blind, randomized, placebo controlled study design
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Discovery Institute
- Responsible party
- Sponsor
- Investigators
- Samuel Klein, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07097506
- Sponsor's protocol ID
- 202503064
- Acronym
- JV
- Status last verified
- Jul 2026
- First submitted
- 24 Jul 2025
- Last updated
- 15 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No