Ketone Pharmacokinetic Study in HFrEF

Sponsor

Duke University (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05757193

Collaborator

National Heart, Lung, and Blood Institute (NHLBI) (NIH), American Heart Association (Other)

Enrollment

Location

Arm

Anticipated Duration (Months)

1.7

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure With Reduced Ejection Fraction	Dietary Supplement: DeltaG	Phase 1

Study Design

Study Type:

Interventional

Anticipated Enrollment :

20 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Participants stratified based on use of background use of SGLT2 inhibitorsParticipants stratified based on use of background use of SGLT2 inhibitors

Masking:

None (Open Label)

Primary Purpose:

Other

Official Title:

Ketone Pharmacokinetic Study in Heart Failure With Reduced Ejection Fraction

Anticipated Study Start Date :

Mar 1, 2023

Anticipated Primary Completion Date :

Mar 1, 2024

Anticipated Study Completion Date :

Mar 1, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Ketone ester All patients will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate. This will begin at 250 mg/kg once with dose escalation to 500 mg/kg in subsequent participants if all safety endpoints are achieved among 5 consecutive participants.	Dietary Supplement: DeltaG (R)-3-hydroxybutyl (R)-3-hydroxybutyrate

Arm

Intervention/Treatment

Experimental: Ketone ester

All patients will receive ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate. This will begin at 250 mg/kg once with dose escalation to 500 mg/kg in subsequent participants if all safety endpoints are achieved among 5 consecutive participants.

Dietary Supplement: DeltaG

(R)-3-hydroxybutyl (R)-3-hydroxybutyrate

Outcome Measures

Primary Outcome Measures

Venous pH [1 hour]
Peripheral blood
Venous pH [2 hours]
Peripheral blood
Venous pH [3 hours]
Peripheral blood
Venous pH [4 hours]
Peripheral blood
Glucose [1 hour]
Peripheral blood
Glucose [2 hours]
Peripheral blood
Glucose [3 hours]
Peripheral blood
Glucose [4 hours]
Peripheral blood
Systolic blood pressure [1 hour]
Taken by blood pressure cuff on the arm
Systolic blood pressure [2 hours]
Taken by blood pressure cuff on the arm
Systolic blood pressure [3 hours]
Taken by blood pressure cuff on the arm
Systolic blood pressure [4 hours]
Taken by blood pressure cuff on the arm
Beta-hydroxybutyrate level [1 hour]
Peripheral blood
Beta-hydroxybutyrate level [2 hours]
Peripheral blood
Beta-hydroxybutyrate level [3 hours]
Peripheral blood
Beta-hydroxybutyrate level [4 hours]
Peripheral blood

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.