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Effects of a Single Oral Dose of KETone Ester ON Exercise Performance in Patients With Chronic Heart Failure (KETONE-HF)

Primary Purpose

Heart Failure With Reduced Ejection Fraction, Heart Failure

Status
Recruiting
Phase
Not Applicable
Locations
Netherlands
Study Type
Interventional
Intervention
Ketone ester drink (DeltaG®, 500 mg/kg body weight)
Taste-matched, isovolumic placebo drink
Sponsored by
University Medical Center Groningen
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With Reduced Ejection Fraction focused on measuring Heart Failure, Ketone Body, HFrEF, Skeletal Muscle Metabolism, Mitochondrial Ketone Oxidation, 31P MRS, Pi/Pcr

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Chronic Heart Failure NYHA II - III
  • LVEF ≤40%
  • Stable for the last 1 month prior to the study

Exclusion Criteria:

  • Age <18 years;
  • Unable or unwilling to undergo exercise MRI (physical disabilities, claustrophobia);
  • Unable to complete the exercise protocol during the screening visit according to the professional opinion of the investigators;
  • Comorbidities which can influence study results such as muscular dystrophies, peripheral artery disease, diabetes mellitus, severe anaemia (defined as Hb ≤6 mmol/L);
  • Pregnant/trying to get pregnant/breastfeeding during the period from the first exercise test until 4 weeks after the last exercise test);
  • Absolute contra-indications to undergo MRI according to the current UMCG protocols and guidelines (e.g. non-conditional medical device, recent device implantation, incompatible ferromagnetic objects in the body).
  • BMI < 16 kg/m2; BMI > 35 kg/m2
  • Unable to understand study procedures;
  • Unable or unwilling to provide informed consent.

Sites / Locations

  • University Medical Center GroningenRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Ketone - Placebo treatment

Placebo - Ketone treatment

Arm Description

Patients will first receive a supplemental drink containing a ketone ester before performing the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time after receiving the placebo treatment.

Patients will first receive a placebodrink before performing the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time after receiving the supplemental drink containing a ketone ester.

Outcomes

Primary Outcome Measures

Phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations from baseline to maximum exercise
Rate and magnitude of change in PCr and Pi concentrations from baseline to maximum exercise.

Secondary Outcome Measures

Rate and magnitude of change in PCr and Pi concentrations during recovery
Rate and magnitude of change in PCr and Pi concentrations during recovery of change in PCr and Pi is expressed as change in Pi/PCr (ΔPi/PCr)
Intramuscular pH
Rates and magnitude of change in intramuscular pH during exercise and recovery
Maximal exercise performance
Maximal exercise performance
Change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise
Change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise

Full Information

First Posted
March 4, 2022
Last Updated
March 7, 2023
Sponsor
University Medical Center Groningen
Collaborators
Netherlands Heart Foundation
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1. Study Identification

Unique Protocol Identification Number
NCT05348460
Brief Title
Effects of a Single Oral Dose of KETone Ester ON Exercise Performance in Patients With Chronic Heart Failure
Acronym
KETONE-HF
Official Title
Effects of a Single Oral Dose of KETone Ester ON Exercise Performance in Patients With Chronic Heart Failure
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Recruiting
Study Start Date
February 15, 2022 (Actual)
Primary Completion Date
June 1, 2023 (Anticipated)
Study Completion Date
June 1, 2023 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University Medical Center Groningen
Collaborators
Netherlands Heart Foundation

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
In a randomized, double-blind, placebo-controlled cross-over design, subjects will either receive a supplemental drink containing a commercially available ketone ester (DeltaG®, 500 mg/kg body weight), or a taste matched, isovolumic placebodrink and will then perform the 31phosphorus Magnetic Resonance Spectroscopy (31P MRS) exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.
Detailed Description
The goal of this study is to investigate if oral ketone supplementation stimulates mitochondrial ATP production and improves exercise performance in patients with chronic HF. In a randomized, double-blind, placebo-controlled cross-over design, subjects will either receive a supplemental drink containing a commercially available ketone ester (DeltaG®, 500 mg/kg body weight), or a taste matched, isovolumic placebodrink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment. Endpoints include rate and magnitude of change in phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations from baseline to maximum exercise, rate and magnitude of change in PCr and Pi concentrations during recovery, rates and magnitude of change in intramuscular pH during exercise and recovery, maximal exercise performance and change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With Reduced Ejection Fraction, Heart Failure
Keywords
Heart Failure, Ketone Body, HFrEF, Skeletal Muscle Metabolism, Mitochondrial Ketone Oxidation, 31P MRS, Pi/Pcr

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Model Description
Randomized, double-blind, placebo-controlled cross-over design
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Double-blind masking
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Ketone - Placebo treatment
Arm Type
Other
Arm Description
Patients will first receive a supplemental drink containing a ketone ester before performing the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time after receiving the placebo treatment.
Arm Title
Placebo - Ketone treatment
Arm Type
Other
Arm Description
Patients will first receive a placebodrink before performing the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time after receiving the supplemental drink containing a ketone ester.
Intervention Type
Dietary Supplement
Intervention Name(s)
Ketone ester drink (DeltaG®, 500 mg/kg body weight)
Intervention Description
In a double blind fashion, subjects will receive a ketone ester drink ór a taste-matched, isovolumic placebo drink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.
Intervention Type
Dietary Supplement
Intervention Name(s)
Taste-matched, isovolumic placebo drink
Intervention Description
In a double blind fashion, subjects will receive a ketone ester drink ór a taste-matched, isovolumic placebo drink and will then perform the 31P MRS exercise protocol. After 1-2 weeks, subjects will cross-over and repeat the 31P MRS exercise protocol, this time receiving the other treatment.
Primary Outcome Measure Information:
Title
Phosphocreatine (PCr) and inorganic phosphate (Pi) concentrations from baseline to maximum exercise
Description
Rate and magnitude of change in PCr and Pi concentrations from baseline to maximum exercise.
Time Frame
During study-visit
Secondary Outcome Measure Information:
Title
Rate and magnitude of change in PCr and Pi concentrations during recovery
Description
Rate and magnitude of change in PCr and Pi concentrations during recovery of change in PCr and Pi is expressed as change in Pi/PCr (ΔPi/PCr)
Time Frame
During study visit
Title
Intramuscular pH
Description
Rates and magnitude of change in intramuscular pH during exercise and recovery
Time Frame
During study visit
Title
Maximal exercise performance
Description
Maximal exercise performance
Time Frame
During study visit
Title
Change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise
Description
Change in concentrations of beta-hydroxybutyrate and other metabolites before consumption of the supplemental drink, after consumption of the supplemental drink and after exercise
Time Frame
During study visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Chronic Heart Failure NYHA II - III LVEF ≤40% Stable for the last 1 month prior to the study Exclusion Criteria: Age <18 years; Unable or unwilling to undergo exercise MRI (physical disabilities, claustrophobia); Unable to complete the exercise protocol during the screening visit according to the professional opinion of the investigators; Comorbidities which can influence study results such as muscular dystrophies, peripheral artery disease, diabetes mellitus, severe anaemia (defined as Hb ≤6 mmol/L); Pregnant/trying to get pregnant/breastfeeding during the period from the first exercise test until 4 weeks after the last exercise test); Absolute contra-indications to undergo MRI according to the current UMCG protocols and guidelines (e.g. non-conditional medical device, recent device implantation, incompatible ferromagnetic objects in the body). BMI < 16 kg/m2; BMI > 35 kg/m2 Unable to understand study procedures; Unable or unwilling to provide informed consent.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Suzanne Voorrips, MD
Phone
0031503614023
Email
s.n.voorrips@umcg.nl
First Name & Middle Initial & Last Name or Official Title & Degree
Daan Westenbrink, MD PhD
Phone
0031503614023
Email
b.d.westenbrink@umcg.nl
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Daan Westenbrink, MD PhD
Organizational Affiliation
Unversity Medical Center Groningen
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Medical Center Groningen
City
Groningen
ZIP/Postal Code
9713GZ
Country
Netherlands
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Suzanne Voorrips, MD
Phone
0031503614023
Email
s.n.voorrips@umcg.nl
First Name & Middle Initial & Last Name & Degree
Daan Westenbrink, MD PhD
Phone
0031503614023
Email
b.d.westenbrink@umcg.nl

12. IPD Sharing Statement

Learn more about this trial

Effects of a Single Oral Dose of KETone Ester ON Exercise Performance in Patients With Chronic Heart Failure

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