Exercise AdaptationsPhase 2NCT05932420
Role of Intermittent Exogenous Ketosis in the Physiological and Muscular Adaptive Response to Endurance Training
A Phase 2 study testing Ketone ester in people with Exercise Adaptations, run by KU Leuven at 1 site in Belgium.
Trial summary
In a recent study (Poffé et al., 2019), we demonstrated that increasing the concentration of ketone bodies in the blood through the ingestion of a ketone ester (KE) post-exercise and just before sleeping time during a 3-week overtraining period resulted in suppression of the physiological symptoms of overtraining. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Exercise Adaptations
- What is being tested?
- Ketone ester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteBelgium
- Study dates
- 1 Oct 2022to 31 Dec 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Physically fit and regularly involved in physical activity (2-5 exercise sessions of > 30min per week)
- Good health status confirmed by a medical screening
- VO2max higher than 50 ml.min-1.kg-1
- Body Mass Index (BMI) between 18 and 25
- Normal sleep pattern as assessed by the Pittsburgh Sleep Quality Index (PSQI, appendix 2)
Who cannot join
- Any kind of injury/pathology that is a contra-indication to perform high-intensity exercise
- Intake of any medication or nutritional supplement that is known to affect exercise performance or sleep
- Intake of analgesics, anti-inflammatory agents, or supplementary anti-oxidants, from 2 weeks prior to the start of the study.
- Night-shifts or travel across time zones in the month preceding the study
- Blood donation within 3 months prior to the start of the study
- Smoking
Show all 9Show fewer
- More than 3 alcoholic beverages per day or more than one glass if wine per day
- Involvement in elite athletic training at a semi-professional or professional level
- Any other argument to believe that the subject is unlikely to successfully complete the full study protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Role of Intermittent Exogenous Ketosis in the Physiological and Muscular Adaptive Response to Endurance Training. A Study in Young, Male Volunteers.
In a recent study (Poffé et al., 2019), we demonstrated that increasing the concentration of ketone bodies in the blood through the ingestion of a ketone ester (KE) post-exercise and just before sleeping time during a 3-week overtraining period resulted in suppression of the physiological symptoms of overtraining. Consistent KE intake improved endurance performance, positively affected the autonomic regulation of the heart, suppressed the increase of nocturnal sympathetic activity, and increased spontaneous energy intake. In addition, KE intake had a positive effect on muscular adaptive response, as evidenced by the significantly increased muscular angiogenesis. Therefore, in this study, we aim to investigate whether the oral administration of ketones after exercise and just before bedtime also has a positive effect on the adaptive response during a well-dosed endurance training program. Since suppression of nocturnal sympathetic activity can positively influence sleep quality, we will also study the effect of KE and the training period on sleep quality.
To investigate this, we will use a randomized, placebo-controlled parallel research design. Well-trained male cyclists will participate in a fully controlled intervention period of 8 weeks. During the intervention period, participants will follow a supervised cycling training program (5-7 training sessions per week) with a gradual buildup aimed at improving endurance capacity.
Throughout the intervention period, participants will ingest 25g ketone ester or a corresponding placebo after each training session and 30 minutes before bedtime. Endurance performance will be evaluated before the start of the training period (pretest), after week 3 (midtest), after week 7 (posttest) of the training period, and at the end of the training intervention (posttest+taper). Additionally, blood samples will be taken at the pre-test and post-test to analyze markers of hormonal status and inflammation. Muscle biopsies will be taken from the vastus lateralis muscle of the right leg at pretest and posttest to analyze cross-sectional area, muscle fiber typing, angiogenesis, protein synthesis and degradation, mitochondrial function, and energy substrate concentrations. One month after the intervention period, an additional biopsy will be taken to study changes in gene expression (epigenetic modifications). Sleep will be evaluated via polysomnography (PSG) at the pretest, midtest and posttest. Finally, before and after the training period, resting and exercise echocardiography will be taken to investigate investigate structural and morphological changes of the heart.
- Conditions
- Exercise Adaptations
- Being tested
- Placebo, Ketone ester
- Keywords
- ketone bodies, Exercise adaptations, Sleep
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDietary supplement
16.4g pure medium triglyceride oil mixed with 1 mM of bitter sucrose octaacetate. A dose of 25g of the placebo drink is provided immediately after each training session and 30 minutes before sleeptime throughout the training period.
Ketone esterDietary supplement
A dose of 25g of ketone ester after each training session and 30 minutes before sleeptime throughout the training period.
| Study group | Role | What they receive |
|---|---|---|
| Control group | Placebo comparator | Placebo is provided Receives: Dietary Supplement: Placebo |
| Experimental groep | Experimental | Ketone ester is provided Receives: Dietary Supplement: Ketone ester |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in mean power output during a 30min cycling time trial
Change in mean power output during a self-paced 30 min cycling time trial on a cyling ergometer
Measured: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention) - Posttest+taper (after week 8 of the training intervention)
Change in capillarization of the musculus vastus lateralis
Change in capillarization (CFPE-index) of the musculus vastus lateralis
Measured: Pretest (before the start of the training intervention) - Posttest (after week 7 of the training intervention)
Change in sleep efficiency
Change in sleep efficiency measured by polysomnography
Measured: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in REM sleep
Change in REM sleep measured by polysomnography
Measured: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Secondary outcomes (4)
Change in the nocturnal urinary excretion of dopamine
Change in the nocturnal urinary excretion of dopamine
Measured: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in the nocturnal urinary excretion of noradrenaline
Change in the nocturnal urinary excretion of noradrenaline
Measured: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in the nocturnal urinary excretion of adrenaline
Change in the nocturnal urinary excretion of adrenaline
Measured: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in maximal oxygen uptake
Change in maximal oxygen uptake measured during a maximal incremental exercise test on a cycling ergometer
Measured: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2023
- Study start1 Oct 2022
- Primary completion1 May 2023
- Study completion31 Dec 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Exercise AdaptationsStudies of the same condition, open and under way.
- More trials run by KU LeuvenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- KU Leuven
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ruben Robberechts, KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05932420
- Sponsor's protocol ID
- S66150
- Status last verified
- Jun 2023
- First submitted
- 27 Jun 2023
- Last updated
- 6 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Poffe C, Ramaekers M, Van Thienen R, Hespel P. Ketone ester supplementation blunts overreaching symptoms during endurance training overload. J Physiol. 2019 Jun;597(12):3009-3027. doi: 10.1113/JP277831. Epub 2019 May 22.
PubMed 31039280Robberechts R, Albouy G, Hespel P, Poffe C. Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep after Strenuous Exercise. Med Sci Sports Exerc. 2023 Nov 1;55(11):2064-2074. doi: 10.1249/MSS.0000000000003231. Epub 2023 Jun 1.
PubMed 37259248
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Role of Intermittent Exogenous Ketosis in the Physiological and Muscular Adaptive Response to Endurance Training. A Study in Young, Male Volunteers.
- ClinicalTrials.gov ID
- NCT05932420
- Acronym / sponsor ID
- S66150
- Conditions
- Exercise Adaptations
- Keywords
- ketone bodies, Exercise adaptations, Sleep
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (actual)
- Lead sponsor
- KU LeuvenUniversity, hospital or other
- Study start
- 1 Oct 2022 (actual)
- Primary completion
- 1 May 2023 (actual)
- Study completion
- 31 Dec 2023 (estimated)
- First posted
- 6 Jul 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In a recent study (Poffé et al., 2019), we demonstrated that increasing the concentration of ketone bodies in the blood through the ingestion of a ketone ester (KE) post-exercise and just before sleeping time during a 3-week overtraining period resulted in suppression of the physiological symptoms of overtraining. Consistent KE intake improved endurance performance, positively affected the autonomic regulation of the heart, suppressed the increase of nocturnal sympathetic activity, and increased spontaneous energy intake. In addition, KE intake had a positive effect on muscular adaptive response, as evidenced by the significantly increased muscular angiogenesis. Therefore, in this study, we aim to investigate whether the oral administration of ketones after exercise and just before bedtime also has a positive effect on the adaptive response during a well-dosed endurance training program. Since suppression of nocturnal sympathetic activity can positively influence sleep quality, we will also study the effect of KE and the training period on sleep quality.
To investigate this, we will use a randomized, placebo-controlled parallel research design. Well-trained male cyclists will participate in a fully controlled intervention period of 8 weeks. During the intervention period, participants will follow a supervised cycling training program (5-7 training sessions per week) with a gradual buildup aimed at improving endurance capacity.
Throughout the intervention period, participants will ingest 25g ketone ester or a corresponding placebo after each training session and 30 minutes before bedtime. Endurance performance will be evaluated before the start of the training period (pretest), after week 3 (midtest), after week 7 (posttest) of the training period, and at the end of the training intervention (posttest+taper). Additionally, blood samples will be taken at the pre-test and post-test to analyze markers of hormonal status and inflammation. Muscle biopsies will be taken from the vastus lateralis muscle of the right leg at pretest and posttest to analyze cross-sectional area, muscle fiber typing, angiogenesis, protein synthesis and degradation, mitochondrial function, and energy substrate concentrations. One month after the intervention period, an additional biopsy will be taken to study changes in gene expression (epigenetic modifications). Sleep will be evaluated via polysomnography (PSG) at the pretest, midtest and posttest. Finally, before and after the training period, resting and exercise echocardiography will be taken to investigate investigate structural and morphological changes of the heart.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control group | Placebo comparator | Dietary Supplement: PlaceboPlacebo is provided |
| Experimental groep | Experimental | Dietary Supplement: Ketone esterKetone ester is provided |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Physically fit and regularly involved in physical activity (2-5 exercise sessions of > 30min per week)
- Good health status confirmed by a medical screening
- VO2max higher than 50 ml.min-1.kg-1
- Body Mass Index (BMI) between 18 and 25
- Normal sleep pattern as assessed by the Pittsburgh Sleep Quality Index (PSQI, appendix 2)
Key exclusion criteria (9 listed)
- Any kind of injury/pathology that is a contra-indication to perform high-intensity exercise
- Intake of any medication or nutritional supplement that is known to affect exercise performance or sleep
- Intake of analgesics, anti-inflammatory agents, or supplementary anti-oxidants, from 2 weeks prior to the start of the study.
- Night-shifts or travel across time zones in the month preceding the study
- Blood donation within 3 months prior to the start of the study
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Placebo16.4g pure medium triglyceride oil mixed with 1 mM of bitter sucrose octaacetate. A dose of 25g of the placebo drink is provided immediately after each training session and 30 minutes before sleeptime throughout the training period. | Dietary supplement | Control group |
| Ketone esterA dose of 25g of ketone ester after each training session and 30 minutes before sleeptime throughout the training period. | Dietary supplement | Experimental groep |
Primary outcome
Change in mean power output during a 30min cycling time trial
Time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention) - Posttest+taper (after week 8 of the training intervention)
Change in mean power output during a self-paced 30 min cycling time trial on a cyling ergometer
Change in capillarization of the musculus vastus lateralis
Time frame: Pretest (before the start of the training intervention) - Posttest (after week 7 of the training intervention)
Change in capillarization (CFPE-index) of the musculus vastus lateralis
Change in sleep efficiency
Time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in sleep efficiency measured by polysomnography
Change in REM sleep
Time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in REM sleep measured by polysomnography
4 secondary outcomes
Change in the nocturnal urinary excretion of dopamine
Time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in the nocturnal urinary excretion of noradrenaline
Time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in the nocturnal urinary excretion of adrenaline
Time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Change in maximal oxygen uptake
Time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2023.
- Background: PubMed 31039280Poffe C, Ramaekers M, Van Thienen R, Hespel P. Ketone ester supplementation blunts overreaching symptoms during endurance training overload. J Physiol. 2019 Jun;597(12):3009-3027. doi: 10.1113/JP277831. Epub 2019 May 22.
- Background: PubMed 37259248Robberechts R, Albouy G, Hespel P, Poffe C. Exogenous Ketosis Improves Sleep Efficiency and Counteracts the Decline in REM Sleep after Strenuous Exercise. Med Sci Sports Exerc. 2023 Nov 1;55(11):2064-2074. doi: 10.1249/MSS.0000000000003231. Epub 2023 Jun 1.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ketone ester in people with Exercise Adaptations, run by KU Leuven at 1 site in Belgium.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 6 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in mean power output during a 30min cycling time trial (time frame: Pretest (before the start of the training intervention) - Midtest (after week 3 of the training intervention) - Posttest (after week 7 of the training intervention) - Posttest+taper (after week 8 of the training intervention)). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05932420, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jul 2023.