Ketone Pharmacokinetic Study in HFrEF

Ketone Pharmacokinetic Study in Heart Failure With Reduced Ejection Fraction

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Reduced Ejection Fraction
• Intervention / Treatment: Dietary supplement: DeltaG (250 mg/kg); Dietary supplement: DeltaG (500 mg/kg)

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 250 mg/kg ketone ester; The first 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 250 mg/kg.	Dietary supplement: DeltaG (250 mg/kg); 250 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
Experimental: 500 mg/kg ketone ester; The second 5 patients within each SGLT2i stratum will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 500 mg/kg.	Dietary supplement: DeltaG (500 mg/kg); 500 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Venous pH Measured Via Peripheral Blood	The pH scale ranges from 0 to 14, with 7 being neutral. Each number on the pH scale represents a ten-fold change in the acidity or basicity of a solution.	1 hour
Glucose Level Measured Via Peripheral Blood		1 hour
Systolic Blood Pressure	Taken by blood pressure cuff on the arm	1 hour
Beta-hydroxybutyrate (BHB) Level Measured Via Peripheral Blood	BHB is a chemical that is made by the body. It provides energy when not enough carbohydrates or sugars have been eaten.	1 hour

Collaborators and Investigators

• Sponsor: Duke University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); American Heart Association
• Investigators: Principal Investigator: Senthil Selvaraj, MD, MSTR, MA, Duke University

Study record dates

Study Major Dates

• Study Start (Actual): June 2, 2023
• Primary Completion (Actual): January 11, 2024
• Study Completion (Actual): January 11, 2024

Study Registration Dates

• First Submitted: February 24, 2023
• First Submitted That Met QC Criteria: February 24, 2023
• First Posted (Actual): March 7, 2023

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: metabolites; metabolomics; ketone ester; DeltaG; ketoacidosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: Pro00111723; K23HL161348 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No