KetosisNCT06097754
Intermittent Exogenous Ketosis (IEK) at High Altitude
A study testing Ketone ester in people with Ketosis and Hypoxia, run by Jozef Stefan Institute at 2 sites in 2 countries.
Trial summary
Altitude-related hypoxia decreases human functional capacity, especially during exercise. Even with prolonged acclimatization, the physiological adaptations are insufficient to preserve exercise capacity, especially at higher altitudes completely. Read more about this study
- Who is it for?
- Ages 18 to 35 yearsHealthy volunteers can take part
- What is being tested?
- Ketone ester
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 35 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 18 Sep 2023to 30 Jun 2024
- Phase
- Interventional
- 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
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Males or females between 18 and 35 years old
- Body Mass Index (BMI) between 18 and 25
- Physically fit and regularly involved in physical activity (2-5 exercise sessions of > 30min per week)
- Good health status confirmed by a medical screening
- Non smoking
Who cannot join
- Any kind of injury/pathology that is a contra-indication for hypoxic exposure and/or 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 antioxidants, from 2 weeks prior to the start of the study.
- Recent residence or training under hypoxia; more than 7 days exposure to altitude > 2000m during a period of 3 months preceding 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
Show all 10Show fewer
- Smoking
- More than 3 alcoholic beverages 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
2 sites in 2 countries.
2 sites in 2 countries
About this study
Official title: Intermittent Exogenous Ketosis (IEK): A Novel Strategy to Improve Hypoxic Tolerance and Adaptation
Altitude-related hypoxia decreases human functional capacity, especially during exercise. Even with prolonged acclimatization, the physiological adaptations are insufficient to preserve exercise capacity, especially at higher altitudes completely. Consequently, there has been an ongoing search for various interventions to mitigate the negative effects of hypoxia on human performance and functional capacity. Interestingly, early data in rodents and humans indicate that intermittent exogenous ketosis (IEK) by ketone ester intake improves hypoxic tolerance, i.e.by facilitating muscular and neuronal energy homeostasis and reducing oxidative stress. Furthermore, there is evidence to indicate that hypoxia elevates the contribution of ketone bodies to adenosine-triphosphate (ATP) generation, substituting glucose and becoming a priority fuel for the brain. Nevertheless, it is reasonable to postulate that ketone bodies might also facilitate long-term acclimation to hypoxia by upregulation of both hypoxia-inducible factor-1α and stimulation of erythropoietin production.
The present project aims to comprehensively investigate the effects of intermittent exogenous ketosis on physiological, cognitive, and functional responses to acute and sub-acute exposure to altitude/hypoxia during rest, exercise, and sleep in healthy adults. Specifically, we aim to elucidate 1) the effects of acute exogenous ketosis during submaximal and maximal intensity exercise in hypoxia, 2) the effects of exogenous ketosis on sleep architecture and quality in hypoxia, and 3) the effects of exogenous ketosis on hypoxic tolerance and sub-acute high-altitude adaptation. For this purpose, a placebo-controlled clinical trial (CT) in hypobaric hypoxia (real high altitude) corresponding to 3375 m a.s.l. (Rifugio Torino, Courmayeur, Italy) will be performed with healthy individuals to investigate both the functional effects of the tested interventions and elucidate the exact physiological, cellular, and molecular mechanisms involved in acute and chronic adaptation to hypoxia. The generated output will not only provide novel insight into the role of ketone bodies under hypoxic conditions but will also be of applied value for mountaineers and athletes competing at altitude as well as for multiple clinical diseases associated with hypoxia.
- Being tested
- Ketone ester, Placebo
- Keywords
- Acclimatization, Altitude, Cardiorespiratory, Cerebrovascular, Exercise, Ketone, Acute Mountain Sickness, Sleep, Cognitive
- Medical subject headings
- Ketosis, Hypoxia, Motor Activity, Altitude Sickness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ketone esterDietary supplement
Ketone ester: A total of 300g ketone ester supplementation will be provided in one of the 72h experimental sessions in order to establish intermittent exogenous ketosis. Sucralose (5% w/w) is added to the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate
Hypobaric hypoxia: 72 hours experimental protocol conducted at terrestrial altitude
PlaceboDietary supplement
Placebo: Water, 5% sucralose (w/w), octaacetate (1 mM)
Hypobaric hypoxia: 72 hours experimental protocol conducted at terrestrial altitude
| Study group | Role | What they receive |
|---|---|---|
| Ketone group | Experimental | Ketone esters will be provided Receives: Dietary Supplement: Ketone ester |
| Control | Placebo comparator | Ketone placebo will be provided Receives: Dietary Supplement: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cerebrovascular reactivity to carbon dioxide (CO2)
Subjects will breathe 4 min 3% CO2 and 4 min 6% CO2 separated by 4 min of breathing ambient air. The middle cerebral artery will be continuously recorded by transcranial Doppler.
Measured: On Day 1 at sea level (in normoxia). On Day 2 (36 hours after) of exposure to hypobaric hypoxia.
Cognitive function
Cognitive function will be assessed by the computerized psychometric test battery: The Psychology Experiment Building Language (PEBL). The following cognitive tests will be used: The color-stroop test (measures attention, processing speed, and inhibitory control; the time it takes to complete the task and the accuracy of the responses; the number of correct and incorrect responses), the digit-span test (measures an individual's working memory capacity and short-term memory; the score of correctly remembered digit span), the ppvt test (measures the reaction time, attention, concentration; the time to react on the visual signal) the fitts test (measures the hand-eye coordination, fine motor skills, concentration; time to position the target) and the timewall test (measures the reasoning, calculating, reaction time, strategy and problem-solving; estimate the time when a moving target will reach a location behind a wall).
Measured: On Day 1 at sea-level (in normoxia). On Day 0 and Day 2 (4 hours and 48 hours) after exposure to hypobaric hypoxia, respectively.
Acute Mountain Sickness (AMS)
Acute Mountain Sickness (AMS) will be assessed by the Lake Louise scale. The symptoms measured on the test include headache, gastrointestinal upset, fatigue/weakness, dizziness/light-headedness, and sleep disturbance. These are rated with an intensity level from 0 (the lowest) to 3 (the highest). A total score that is ≥3, including a headache, is indicative of AMS.
Measured: Every day at 9.00 p.m. (before sleep) and at 6.15 a.m. (upon waking) in normoxia and hypobaric hypoxia, respectively.
Change in lung function estimating forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1).
Lung function will be assessed by FVC and FEV1.
Measured: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Change in lung function estimating peak expiratory flow (PEF).
Lung function will be assessed by PEF.
Measured: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Change in lung function
Lung function will be assessed by the FEV1/FVC ratio.
Measured: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Heart rate response to exercise
Heart rate (HR, bpm) will be continuously monitored during different exercise bouts of a variety of intensities (moderate and heavy intensities will be used).
Measured: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Respiratory response to exercise
Oxygen consumption (VO2, L/min and mL/min/kg) will be continuously monitored during different exercise bouts of variety intensities (moderate and heavy intensities will be used).
Measured: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Changes in muscular oxygenation during exercise
Muscle oxygenation/deoxygenation will be continuously recorded during each exercise bout by Near Infra-Red Spectroscopy (NIRS) placed on the vastus lateralis. NIRS measure the quantity of oxygenated and deoxygenated haemoglobin and myoglobin (microM) in the investigated areas (vastus lateralis).
Measured: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Changes in cerebral oxygenation during exercise
Brain oxygenation/deoxygenation will be continuously recorded during each exercise bout by Near Infra-Red Spectroscopy (NIRS) placed at the frontal levels. NIRS measure the quantity of oxygenated and deoxygenated haemoglobin (microM) in the investigated areas (prefrontal cortex).
Measured: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Changes in the rate of muscular oxygen consumption (mV#O2)
Muscle oxygen consumption will be assessed using a previously validated protocol. Briefly, a Near Infra-Red Spectroscopy (NIRS) optode will be placed on the vastus lateralis muscle. Before the protocol, an ischemic calibration will be performed to normalize the NIRS signals by inflating the blood pressure cuff to 250-300 mmHg for a maximum of 5 min. Resting mV#O2 will be assessed from the decrease in muscle oxygenation which accompanies the arterial occlusion.Then, each subject will perform a 3 x 6 minutes moderate-intensity exercise, 8 minutes heavy-intensity exercise and graded exercise test. To measure the recovery of oxygen consumption after exercise, subject will have a series of arterial occlusion as follows: 5 occlusions 5sec on-5sec off, 5 occlusions 5sec on-5sec off, and 5 occlusions 10 sec on-20 sec off.
Measured: Every day before each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Duration of different sleep stages
Polysomnography will be used to assess the duration of the different sleep stages.
Measured: Throughout the entire duration of the night, up to 8 hours after individual bedtime (between 10 p.m. and 6 a.m.). On Day 0 in normoxia. On Day 0 and Day 2 in hypobaric hypoxia.
Changes in oxidative stress markers in the blood
Oxidative stress markers concentration will be measured on collected venous blood sample.
Measured: Blood samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Change in salivary cortisol concentration
Cortisol concentration will be measured on collected saliva samples.
Measured: Saliva samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Change in hydration status
Urine samples will be assessed using urine specific gravity.
Measured: Urine samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Baroreflex sensitivity
At sea level: subjects will breath 6 min normal ambient air (21% O2, 0.03% CO2), 6 hypoxic normocapnic (13.8% O2, 0.03% CO2), and 6 min normoxic hypercapnic (21% O2, 3% CO2) air.
At high altitude: subjects will breath 6 min hypobaric hypoxic (21% O2, 0.03% CO2), hypobaric normoxic (32% O2, 0.03% CO2), hypobaric normoxic hypercapnic (32% O2, 3% CO2) air.
Measured: Within 24 h hours after exposure to normoxia and hypobaric hypoxia, respectively
Change in nocturnal oxygen saturation
Measured using pulse oximetry
Measured: Throughout the entire duration of the night, up to 8 hours after individual bedtime (between 10 p.m. and 6 a.m.). On Day 0 in normoxia. On Day 0 and Day 2 in hypobaric hypoxia.
Absolute amount of nocturnal urinary catecholamine excretion
Measured using ELISA of collected nocturnal urine. Subjects empty bladder before sleep and urine will be collected throughout the entire duration of the night, up to 8 hours. Up to 8 hours from 10 p.m. to 6 a.m. on Day 0 in normoxia and Day 0, Day 1 and Day 2 in hypobaric hypoxia.
Measured: From 10 p.m. to 6 a.m. on Day 0 in normoxia and Day 0, Day 1 and Day 2 in hypobaric hypoxia.
Secondary outcomes (1)
Change in cerebral blood flow in the internal carotid artery
Cerebral blood flow in the internal will be assessed every morning by doppler ultrasound.
Measured: On Day 1 at sea level (in normoxia). On Day 2 (36 hours after) of exposure to hypobaric hypoxia.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Oct 2023
- Study start18 Sep 2023
- Primary completion30 Oct 2023 (estimated)
- Study completion30 Jun 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for KetosisStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 1 group with ketone ester supplementation and 1 group with taste and viscosity matched placebo
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jozef Stefan Institute
- Sponsor type
- University, hospital or other
- Collaborators
- KU Leuven, University of Lausanne
- Responsible party
- Principal investigator, Tadej Debevec, Jozef Stefan Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06097754
- Sponsor's protocol ID
- IEK Weave
- Status last verified
- Oct 2023
- First submitted
- 13 Oct 2023
- Last updated
- 24 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tominec D, Stalmans M, Narang BJ, Millet GP, Poffe C, Debevec T. Exogenous Ketosis during Early Acclimatization at High Altitude: Ventilatory, Cardiovascular and Muscular Responses to Maximal Exercise. Med Sci Sports Exerc. 2025 Nov 1;57(11):2468-2479. doi: 10.1249/MSS.0000000000003791. Epub 2025 Jun 13.
PubMed 40523225
Study at a glance
From the registry record, last updated by the sponsor on 24 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intermittent Exogenous Ketosis (IEK): A Novel Strategy to Improve Hypoxic Tolerance and Adaptation
- ClinicalTrials.gov ID
- NCT06097754
- Acronym / sponsor ID
- IEK Weave
- Keywords
- Acclimatization, Altitude, Cardiorespiratory, Cerebrovascular, Exercise, Ketone, Acute Mountain Sickness, Sleep
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Jozef Stefan InstituteUniversity, hospital or other
- Collaborators
- KU Leuven, University of Lausanne
- Study start
- 18 Sep 2023 (actual)
- Primary completion
- 30 Oct 2023 (estimated)
- Study completion
- 30 Jun 2024 (estimated)
- First posted
- 24 Oct 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.
Altitude-related hypoxia decreases human functional capacity, especially during exercise. Even with prolonged acclimatization, the physiological adaptations are insufficient to preserve exercise capacity, especially at higher altitudes completely. Consequently, there has been an ongoing search for various interventions to mitigate the negative effects of hypoxia on human performance and functional capacity. Interestingly, early data in rodents and humans indicate that intermittent exogenous ketosis (IEK) by ketone ester intake improves hypoxic tolerance, i.e.by facilitating muscular and neuronal energy homeostasis and reducing oxidative stress. Furthermore, there is evidence to indicate that hypoxia elevates the contribution of ketone bodies to adenosine-triphosphate (ATP) generation, substituting glucose and becoming a priority fuel for the brain. Nevertheless, it is reasonable to postulate that ketone bodies might also facilitate long-term acclimation to hypoxia by upregulation of both hypoxia-inducible factor-1α and stimulation of erythropoietin production.
The present project aims to comprehensively investigate the effects of intermittent exogenous ketosis on physiological, cognitive, and functional responses to acute and sub-acute exposure to altitude/hypoxia during rest, exercise, and sleep in healthy adults. Specifically, we aim to elucidate 1) the effects of acute exogenous ketosis during submaximal and maximal intensity exercise in hypoxia, 2) the effects of exogenous ketosis on sleep architecture and quality in hypoxia, and 3) the effects of exogenous ketosis on hypoxic tolerance and sub-acute high-altitude adaptation. For this purpose, a placebo-controlled clinical trial (CT) in hypobaric hypoxia (real high altitude) corresponding to 3375 m a.s.l. (Rifugio Torino, Courmayeur, Italy) will be performed with healthy individuals to investigate both the functional effects of the tested interventions and elucidate the exact physiological, cellular, and molecular mechanisms involved in acute and chronic adaptation to hypoxia. The generated output will not only provide novel insight into the role of ketone bodies under hypoxic conditions but will also be of applied value for mountaineers and athletes competing at altitude as well as for multiple clinical diseases associated with hypoxia.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- 1 group with ketone ester supplementation and 1 group with taste and viscosity matched placebo
| Arm | Type | Receives |
|---|---|---|
| Ketone group | Experimental | Dietary Supplement: Ketone esterKetone esters will be provided |
| Control | Placebo comparator | Dietary Supplement: PlaceboKetone placebo will be provided |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Males or females between 18 and 35 years old
- Body Mass Index (BMI) between 18 and 25
- Physically fit and regularly involved in physical activity (2-5 exercise sessions of > 30min per week)
- Good health status confirmed by a medical screening
- Non smoking
Key exclusion criteria (10 listed)
- Any kind of injury/pathology that is a contra-indication for hypoxic exposure and/or 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 antioxidants, from 2 weeks prior to the start of the study.
- Recent residence or training under hypoxia; more than 7 days exposure to altitude > 2000m during a period of 3 months preceding the study.
- Night-shifts or travel across time zones in the month preceding 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 |
|---|---|---|
| Ketone esterKetone ester: A total of 300g ketone ester supplementation will be provided in one of the 72h experimental sessions in order to establish intermittent exogenous ketosis. Sucralose (5% w/w) is added to the ketone ester (R)-3-hydroxybutyl (R)-3-hydroxybutyrate Hypobaric hypoxia: 72 hours experimental protocol conducted at terrestrial altitude | Dietary supplement | Ketone group |
| PlaceboPlacebo: Water, 5% sucralose (w/w), octaacetate (1 mM) Hypobaric hypoxia: 72 hours experimental protocol conducted at terrestrial altitude | Dietary supplement | Control |
Primary outcome
Cerebrovascular reactivity to carbon dioxide (CO2)
Time frame: On Day 1 at sea level (in normoxia). On Day 2 (36 hours after) of exposure to hypobaric hypoxia.
Subjects will breathe 4 min 3% CO2 and 4 min 6% CO2 separated by 4 min of breathing ambient air. The middle cerebral artery will be continuously recorded by transcranial Doppler.
Cognitive function
Time frame: On Day 1 at sea-level (in normoxia). On Day 0 and Day 2 (4 hours and 48 hours) after exposure to hypobaric hypoxia, respectively.
Cognitive function will be assessed by the computerized psychometric test battery: The Psychology Experiment Building Language (PEBL). The following cognitive tests will be used: The color-stroop test (measures attention, processing speed, and inhibitory control; the time it takes to complete the task and the accuracy of the responses; the number of correct and incorrect responses), the digit-span test (measures an individual's working memory capacity and short-term memory; the score of correctly remembered digit span), the ppvt test (measures the reaction time, attention, concentration; the time to react on the visual signal) the fitts test (measures the hand-eye coordination, fine motor skills, concentration; time to position the target) and the timewall test (measures the reasoning, calculating, reaction time, strategy and problem-solving; estimate the time when a moving target will reach a location behind a wall).
Acute Mountain Sickness (AMS)
Time frame: Every day at 9.00 p.m. (before sleep) and at 6.15 a.m. (upon waking) in normoxia and hypobaric hypoxia, respectively.
Acute Mountain Sickness (AMS) will be assessed by the Lake Louise scale. The symptoms measured on the test include headache, gastrointestinal upset, fatigue/weakness, dizziness/light-headedness, and sleep disturbance. These are rated with an intensity level from 0 (the lowest) to 3 (the highest). A total score that is ≥3, including a headache, is indicative of AMS.
Change in lung function estimating forced vital capacity (FVC) and forced expiratory volume in 1st second (FEV1).
Time frame: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Lung function will be assessed by FVC and FEV1.
Change in lung function estimating peak expiratory flow (PEF).
Time frame: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Lung function will be assessed by PEF.
Change in lung function
Time frame: On Day 1 at sea level and on Day 3 of exposure to hypobaric hypoxia.
Lung function will be assessed by the FEV1/FVC ratio.
Heart rate response to exercise
Time frame: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Heart rate (HR, bpm) will be continuously monitored during different exercise bouts of a variety of intensities (moderate and heavy intensities will be used).
Respiratory response to exercise
Time frame: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Oxygen consumption (VO2, L/min and mL/min/kg) will be continuously monitored during different exercise bouts of variety intensities (moderate and heavy intensities will be used).
Changes in muscular oxygenation during exercise
Time frame: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Muscle oxygenation/deoxygenation will be continuously recorded during each exercise bout by Near Infra-Red Spectroscopy (NIRS) placed on the vastus lateralis. NIRS measure the quantity of oxygenated and deoxygenated haemoglobin and myoglobin (microM) in the investigated areas (vastus lateralis).
Changes in cerebral oxygenation during exercise
Time frame: Every day during each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Brain oxygenation/deoxygenation will be continuously recorded during each exercise bout by Near Infra-Red Spectroscopy (NIRS) placed at the frontal levels. NIRS measure the quantity of oxygenated and deoxygenated haemoglobin (microM) in the investigated areas (prefrontal cortex).
Changes in the rate of muscular oxygen consumption (mV#O2)
Time frame: Every day before each 20-90 min long exercise bout performed between 9 a.m. and 6 p.m.. On Day 0 and Day 1 in normoxia. On Day 0, Day 1, Day 2, and Day 3 in hypobaric hypoxia.
Muscle oxygen consumption will be assessed using a previously validated protocol. Briefly, a Near Infra-Red Spectroscopy (NIRS) optode will be placed on the vastus lateralis muscle. Before the protocol, an ischemic calibration will be performed to normalize the NIRS signals by inflating the blood pressure cuff to 250-300 mmHg for a maximum of 5 min. Resting mV#O2 will be assessed from the decrease in muscle oxygenation which accompanies the arterial occlusion.Then, each subject will perform a 3 x 6 minutes moderate-intensity exercise, 8 minutes heavy-intensity exercise and graded exercise test. To measure the recovery of oxygen consumption after exercise, subject will have a series of arterial occlusion as follows: 5 occlusions 5sec on-5sec off, 5 occlusions 5sec on-5sec off, and 5 occlusions 10 sec on-20 sec off.
Duration of different sleep stages
Time frame: Throughout the entire duration of the night, up to 8 hours after individual bedtime (between 10 p.m. and 6 a.m.). On Day 0 in normoxia. On Day 0 and Day 2 in hypobaric hypoxia.
Polysomnography will be used to assess the duration of the different sleep stages.
Changes in oxidative stress markers in the blood
Time frame: Blood samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Oxidative stress markers concentration will be measured on collected venous blood sample.
Change in salivary cortisol concentration
Time frame: Saliva samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Cortisol concentration will be measured on collected saliva samples.
Change in hydration status
Time frame: Urine samples will be collected on Day 1 in normoxia and Day 1, Day 2 and Day 3 in hypobaric hypoxia at 6 a.m. (upon waking).
Urine samples will be assessed using urine specific gravity.
Baroreflex sensitivity
Time frame: Within 24 h hours after exposure to normoxia and hypobaric hypoxia, respectively
At sea level: subjects will breath 6 min normal ambient air (21% O2, 0.03% CO2), 6 hypoxic normocapnic (13.8% O2, 0.03% CO2), and 6 min normoxic hypercapnic (21% O2, 3% CO2) air. At high altitude: subjects will breath 6 min hypobaric hypoxic (21% O2, 0.03% CO2), hypobaric normoxic (32% O2, 0.03% CO2), hypobaric normoxic hypercapnic (32% O2, 3% CO2) air.
Change in nocturnal oxygen saturation
Time frame: Throughout the entire duration of the night, up to 8 hours after individual bedtime (between 10 p.m. and 6 a.m.). On Day 0 in normoxia. On Day 0 and Day 2 in hypobaric hypoxia.
Measured using pulse oximetry
Absolute amount of nocturnal urinary catecholamine excretion
Time frame: From 10 p.m. to 6 a.m. on Day 0 in normoxia and Day 0, Day 1 and Day 2 in hypobaric hypoxia.
Measured using ELISA of collected nocturnal urine. Subjects empty bladder before sleep and urine will be collected throughout the entire duration of the night, up to 8 hours. Up to 8 hours from 10 p.m. to 6 a.m. on Day 0 in normoxia and Day 0, Day 1 and Day 2 in hypobaric hypoxia.
1 secondary outcome
Change in cerebral blood flow in the internal carotid artery
Time frame: On Day 1 at sea level (in normoxia). On Day 2 (36 hours after) of exposure to hypobaric hypoxia.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Oct 2023.
- Derived from this study: PubMed 40523225Tominec D, Stalmans M, Narang BJ, Millet GP, Poffe C, Debevec T. Exogenous Ketosis during Early Acclimatization at High Altitude: Ventilatory, Cardiovascular and Muscular Responses to Maximal Exercise. Med Sci Sports Exerc. 2025 Nov 1;57(11):2468-2479. doi: 10.1249/MSS.0000000000003791. Epub 2025 Jun 13.
- Individual participant dataSharing planned: No
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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.
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketone ester in people with Ketosis and Hypoxia, run by Jozef Stefan Institute at 2 sites in 2 countries.
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 10 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 24 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Belgium, Slovenia. 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.
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?
Cerebrovascular reactivity to carbon dioxide (CO2) (time frame: On Day 1 at sea level (in normoxia). On Day 2 (36 hours after) of exposure to hypobaric hypoxia.). The study lists 18 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 NCT06097754, which also lists 1 linked publication.
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 24 Oct 2023.