Trial Outcomes & Findings for Acute Effects of Exogenous Ketone Ester Administration in Heart Failure (NCT NCT04633460)
NCT ID: NCT04633460
Last Updated: 2024-11-27
Results Overview
Peak VO2
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
26 participants
Primary outcome timeframe
Assessed 60 minutes after the intervention.
Results posted on
2024-11-27
Participant Flow
Out of 26 consented participants, 5 screen failed and 1 participant withdrew, leading to 20 randomized participants.
Participant milestones
| Measure |
Ketone Ester First, Then Placebo
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis.
10 individuals were randomized to acute dosing of KE first. Then, after approximately 7 day washout, these 10 individuals received acute dosing of placebo.
|
Placebo First, Then Ketone Ester
KE-free solution first, then KE after 7 day washout
placebo drink: KE free placebo drink
10 individuals were randomized to acute dosing of placebo first. Then, after approximately 7 day washout, these 10 individuals received acute dosing of KE.
|
|---|---|---|
|
First Intervention
STARTED
|
10
|
10
|
|
First Intervention
COMPLETED
|
10
|
10
|
|
First Intervention
NOT COMPLETED
|
0
|
0
|
|
Washout
STARTED
|
10
|
10
|
|
Washout
COMPLETED
|
10
|
10
|
|
Washout
NOT COMPLETED
|
0
|
0
|
|
Second Intervention
STARTED
|
10
|
10
|
|
Second Intervention
COMPLETED
|
10
|
10
|
|
Second Intervention
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Acute Effects of Exogenous Ketone Ester Administration in Heart Failure
Baseline characteristics by cohort
| Measure |
Randomized First to Ketone Ester
n=10 Participants
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis.
10 individuals were randomized to ketone ester first, and 10 individuals were randomized to placebo first.
|
Randomized First to Placebo
n=10 Participants
KE-free solution
placebo drink: KE free placebo drink.
10 individuals were randomized to ketone ester first, and 10 individuals were randomized to placebo first.
|
Total
n=20 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
71 years
STANDARD_DEVIATION 7 • n=99 Participants
|
71 years
STANDARD_DEVIATION 10 • n=107 Participants
|
71 years
STANDARD_DEVIATION 8 • n=206 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
4 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
8 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
7 Participants
n=99 Participants
|
6 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Assessed 60 minutes after the intervention.Population: All 20 participants contributed to the data. 10 participants started first in the ketone ester group and then crossed over to placebo, while 10 participants started first in the placebo arm and crossed over the ketone ester.
Peak VO2
Outcome measures
| Measure |
Ketone Ester
n=20 Participants
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=20 Participants
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
Maximal Exercise Capacity (Peak VO2) Assessed by Cardiopulmonary Exercise Testing
|
1.0 L/min
Standard Deviation 0.3
|
1.0 L/min
Standard Deviation 0.3
|
PRIMARY outcome
Timeframe: Assessed 30 minutes after the intervention.Population: All 20 participants contributed to the data. 10 participants started first in the ketone ester group and then crossed over to placebo, while 10 participants started first in the placebo arm and crossed over the ketone ester.
Exercise time at 75% of peak workload
Outcome measures
| Measure |
Ketone Ester
n=20 Participants
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=20 Participants
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
Submaximal Exercise Capacity (Exercise Time at 75% of Peak Workload) Assessed by Cardiopulmonary Exercise Testing.
|
9.7 minutes
Standard Deviation 7.3
|
8.7 minutes
Standard Deviation 4.3
|
SECONDARY outcome
Timeframe: Assessed 60 minutes after the intervention.Population: All participants with available data (13 in ketone ester group and 14 in the placebo group) shown here.
Percent change in systemic vascular resistance with exercise
Outcome measures
| Measure |
Ketone Ester
n=13 Participants
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=14 Participants
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
Percent Change in Systemic Vascular Resistance With Exercise
|
-21.5 Percent change from rest to peak exercis
Standard Deviation 14.7
|
-34.2 Percent change from rest to peak exercis
Standard Deviation 11.5
|
SECONDARY outcome
Timeframe: Assessed 60 minutes after the intervention.Population: All 20 participants contributed to the data. 10 participants started first in the ketone ester group and then crossed over to placebo, while 10 participants started first in the placebo arm and crossed over the ketone ester.
Outcome measures
| Measure |
Ketone Ester
n=20 Participants
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=20 Participants
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
Substrate Utilization (Reflected by the Respiratory Exchange Ratio) Assessed by Cardiopulmonary Exercise Testing.
|
1.09 Ratio
Standard Deviation 0.13
|
1.14 Ratio
Standard Deviation 0.14
|
SECONDARY outcome
Timeframe: Assessed 60 minutes after the intervention.Population: All 20 participants contributed to the data. 10 participants started first in the ketone ester group and then crossed over to placebo, while 10 participants started first in the placebo arm and crossed over the ketone ester.
Outcome measures
| Measure |
Ketone Ester
n=20 Participants
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=20 Participants
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
VO2 Efficiency (Total Work Performed Over Oxygen Consumed) During Submaximal Cardiopulmonary Exercise Testing.
|
6.0 kJ/L O2
Standard Deviation 2.6
|
6.1 kJ/L O2
Standard Deviation 2.9
|
SECONDARY outcome
Timeframe: Assessed throughout the study visit date after the intervention is given (until leaving the research study center that day).Population: All 20 participants contributed to the data. 10 participants started first in the ketone ester group and then crossed over to placebo, while 10 participants started first in the placebo arm and crossed over the ketone ester.
Outcome measures
| Measure |
Ketone Ester
n=20 Participants
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=20 Participants
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
Presence of Exercise-induced Arrhythmias (Significant Atrial or Ventricular Arrhythmias)
|
0 Participants
|
0 Participants
|
Adverse Events
Ketone Ester
Serious events: 1 serious events
Other events: 7 other events
Deaths: 0 deaths
Placebo
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Ketone Ester
n=20 participants at risk
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=20 participants at risk
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Laryngeal inflammation
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
Other adverse events
| Measure |
Ketone Ester
n=20 participants at risk
(R)-3-hydroxybutyl (R)-3-hydroxybutyrate, a ketone ester
Ketone ester: A nutraceutical ketone ester (KE), (R)-3-hydroxybutyl (R)-3-hydroxybutyrate which provides systemic ketosis
|
Placebo
n=20 participants at risk
KE-free solution
placebo drink: KE free placebo drink
|
|---|---|---|
|
Nervous system disorders
Dizziness
|
15.0%
3/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Gastrointestinal disorders
Reflux
|
10.0%
2/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Respiratory, thoracic and mediastinal disorders
Upper respiratory tract infection
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Musculoskeletal and connective tissue disorders
Knee pain
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Nervous system disorders
Headache
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Musculoskeletal and connective tissue disorders
Muscle cramp
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
General disorders
Fatigue
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Blood and lymphatic system disorders
Hematoma
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Cardiac disorders
Hypotension
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Reproductive system and breast disorders
Breast pain
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Cardiac disorders
Heart racing
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Blood and lymphatic system disorders
Pain with blood draw
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
|
Gastrointestinal disorders
Diarrhea
|
0.00%
0/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
5.0%
1/20 • Adverse events were collected the day of the study visit (the day of the first intervention visit, "Day 1", and the day of the second intervention visit, approximately "Day 8").
|
Additional Information
Payman Zamani
Hospital of the University of Pennsylvania
Phone: (215) 662-4000
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place