Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
DeltaG, ketone ester, metabolites, metabolomics, ketoacidosis
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.
Interventions
DIETARY_SUPPLEMENTDeltaG (250 mg/kg)
250 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
DIETARY_SUPPLEMENTDeltaG (500 mg/kg)
500 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
American Heart Association
Duke University
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
NONE
Intervention model description
Participants stratified based on use of background use of SGLT2 inhibitors
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Venous pH Measured Via Peripheral Blood | 1 hour | 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. |
| Glucose Level Measured Via Peripheral Blood | 1 hour | — |
| Systolic Blood Pressure | 1 hour | Taken by blood pressure cuff on the arm |
| Beta-hydroxybutyrate (BHB) Level Measured Via Peripheral Blood | 1 hour | BHB is a chemical that is made by the body. It provides energy when not enough carbohydrates or sugars have been eaten. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited within the Duke University Health System.
Participants by arm
| Arm | Count |
|---|---|
| 250 mg/kg Ketone Ester Participants received ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 250 mg/kg.
DeltaG (250 mg/kg): 250 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate | 10 |
| 500 mg/kg Ketone Ester Participants received ketone ester as (R)-3-hydroxybutyl (R)-3-hydroxybutyrate at 500 mg/kg.
DeltaG (500 mg/kg): 500 mg/kg of (R)-3-hydroxybutyl (R)-3-hydroxybutyrate | 10 |
| Total | 20 |
Baseline characteristics
| Characteristic | 500 mg/kg Ketone Ester | Total | 250 mg/kg Ketone Ester |
|---|---|---|---|
| Age, Continuous | 65.0 years STANDARD_DEVIATION 9 | 64.4 years STANDARD_DEVIATION 8.8 | 63.8 years STANDARD_DEVIATION 9.1 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 1 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 19 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 4 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 14 Participants | 6 Participants |
| Region of Enrollment United States | 10 Participants | 20 Participants | 10 Participants |
| Sex: Female, Male Female | 6 Participants | 9 Participants | 3 Participants |
| Sex: Female, Male Male | 4 Participants | 11 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 10 | 0 / 10 |
| other Total, other adverse events | 1 / 10 | 1 / 10 |
| serious Total, serious adverse events | 0 / 10 | 0 / 10 |
Outcome results
Primary
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.
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 250 mg/kg Ketone Ester | Beta-hydroxybutyrate (BHB) Level Measured Via Peripheral Blood | 1.88 millimolar | Standard Deviation 0.3 |
| 500 mg/kg Ketone Ester | Beta-hydroxybutyrate (BHB) Level Measured Via Peripheral Blood | 2.78 millimolar | Standard Deviation 0.54 |
Primary
Glucose Level Measured Via Peripheral Blood
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 250 mg/kg Ketone Ester | Glucose Level Measured Via Peripheral Blood | 136 mg/dL | Standard Deviation 70 |
| 500 mg/kg Ketone Ester | Glucose Level Measured Via Peripheral Blood | 101 mg/dL | Standard Deviation 45 |
Primary
Systolic Blood Pressure
Taken by blood pressure cuff on the arm
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 250 mg/kg Ketone Ester | Systolic Blood Pressure | 108 mmHg | Standard Deviation 12 |
| 500 mg/kg Ketone Ester | Systolic Blood Pressure | 110 mmHg | Standard Deviation 15 |
Primary
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.
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| 250 mg/kg Ketone Ester | Venous pH Measured Via Peripheral Blood | 7.30 unitless | Standard Deviation 0.04 |
| 500 mg/kg Ketone Ester | Venous pH Measured Via Peripheral Blood | 7.28 unitless | Standard Deviation 0.04 |