Ketone Pharmacokinetic Study in HFrEF

Duke University

Status and phase: Completed; Phase 1

Conditions: Heart Failure With Reduced Ejection Fraction

Treatments: Dietary Supplement: DeltaG (250 mg/kg); Dietary Supplement: DeltaG (500 mg/kg)

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05757193

K23HL161348 (U.S. NIH Grant/Contract)

Pro00111723

Details and patient eligibility

About

The purpose of this study is to test whether an over-the-counter ketone ester drink is well tolerated in people with heart failure on, and not on, a heart failure medication class called SGLT2 inhibitors. The research team is trying to determine the safest dose of Delta G. The study has a single visit. Participants will be served a light breakfast with the study drink, a physical exam will be conducted, and the study team will obtain information about demographics and medical history. The study team will draw blood intravenously up to eight times over the course of the half-day visit.

Enrollment: 20 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Diagnosis of HFrEF (ejection fraction<=45%)
• Systolic blood pressure greater >=90 mmHg

Exclusion criteria

• Intentional ketogenic (high fat, low carbohydrate) diet (must be off ketogenic diet for >7 days prior to visit)
• Significant liver disease (cirrhosis) or alcohol abuse disorder (>14 drinks/week).
• Unique cardiomyopathies: infiltrative/hypertrophic cardiomyopathy, pericardial disease, or other cardiomyopathies that in the investigator's opinion have unique treatment options that would be less likely to be affected by ketone therapy.
• Estimated glomerular filtration rate<25 mL/min/1.73 m2 as the most recent value in the last year.
• Type 1 diabetes mellitus
• Use of ventricular assist device, history of heart transplant, or use of continuous inotropes
• Pregnant women. Due to unknown affects of nutritional ketosis in pregnant women, pregnancy will be an exclusion. Accordingly, women of childbearing age with a menstrual cycle within the past year will be asked to submit a urine specimen for pregnancy testing.

Trial design

Primary purpose: Other

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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20 participants in 2 patient groups

250 mg/kg ketone ester

Experimental group

Description:

The first 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 250 mg/kg.

Treatment:

Dietary Supplement: DeltaG (250 mg/kg)

500 mg/kg ketone ester

Experimental group

Description:

The second 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 500 mg/kg.

Treatment:

Dietary Supplement: DeltaG (500 mg/kg)