Cognitive Ability, GeneralHYPOX-AGENCT06874387
Investigating the Combined Effects of Intermittent Hypoxia and Exercise on Cognitive and Cerebral Function in Middle-Aged Adults
A study testing Hypoxia, intermittent and physical exercise in people with Cognitive Ability, General and Brain Health, run by Ayoub Boulares.
Trial summary
This study investigates whether intermittent hypoxia (IH) and physical activity (PA), either alone or in combination (simultaneously or sequentially), can improve cognitive function and brain health in middle-aged adults (50-65 years old). Read more about this study
- Who is it for?
- Ages 50 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Cognitive Ability, General, Brain Health, Cerebral Oxygenation
- What is being tested?
- Hypoxia, intermittent and physical exercise
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 176 participants
- Where
- No sites listed yet
- Study dates
- 1 Apr 2025to 30 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 50 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Adults aged 50 to 65 years (male and female)
- Montreal Cognitive Assessment (MoCA) score ≥ 24
- No participation in any structured exercise intervention in the last 6 months
- No exposure to altitudes above 1,500 m in the preceding 3 months
- No chronic kidney, cardiovascular, metabolic, neurological, or orthopedic -disease
- No history of significant respiratory conditions (e.g., asthma, exercise-induced -bronchospasm, dyspnea on exertion)
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- No current immunosuppressive treatment (e.g., corticosteroids, antidepressants)
- No history of cancer or arthritis treatments
- No recent blood donation (within the last 2 months)
- Must be covered by a Social Security system or equivalent
- Signed informed consent after receiving clear and transparent study information
- Eligibility confirmed by a medical doctor during the inclusion process
Who cannot join
- Active smoking
- Major cardiovascular complications within the last 3 months (e.g., myocardial i-infarction, unstable angina, severe arrhythmias)
- Severe hypertension (≥180 mmHg systolic or ≥110 mmHg diastolic)
- Chronic respiratory insufficiency (e.g., COPD, sleep apnea)
- Diabetes mellitus
- Need for continuous or intermittent oxygen therapy
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- Participation in another clinical study at the same time
- Use of corticosteroids or other systemic immunosuppressants
- Any condition compromising safety or study compliance, as determined by the medical team
- Pregnancy or breastfeeding
- Legal or administrative protections (e.g., individuals under guardianship, persons deprived of liberty)
- High baseline physical activity levels (PASE score >90 indicating moderate-to-intense physical activity)
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Towards a Better Understanding of the Combination of Intermittent Hypoxia and Physical Exercise: Comparison of Effects on Cognitive and Cerebral Capacities in Middle-Aged Adults
This study investigates whether intermittent hypoxia (IH) and physical activity (PA), either alone or in combination (simultaneously or sequentially), can improve cognitive function and brain health in middle-aged adults (50-65 years old). The hypothesis is that (1) each intervention alone (IHT or PA) provides cognitive benefits and (2) combining IHT with PA may yield additive or synergistic effects, particularly when administered simultaneously rather than sequentially. By comparing these distinct interventions, the study aims to determine which approach best preserves or enhances cognitive performance in middle-aged adults. Findings from this research may inform non-pharmacological strategies to promote healthy aging and reduce the risk of age-related cognitive decline.
Read the detailed description
Rapid demographic aging worldwide is driving a surge in age-related conditions, including neurodegenerative diseases and cognitive disorders. Projections estimate that the number of people living with dementia could reach 78 million by 2030 and 139 million by 2050, underscoring the urgent need for effective, non-pharmacological strategies to preserve brain health. Intermittent hypoxia (IH) and physical activity (PA) are two promising interventions that may help prevent or mitigate cognitive decline. IH-an approach involving repeated cycles of reduced oxygen (11-16% FiO₂) followed by normoxic recovery-has shown benefits across diverse health domains (cardiovascular, metabolic, respiratory, and neurological), potentially through mechanisms such as the activation of Hypoxia-Inducible Factor (HIF), enhanced vascular endothelial growth factor (VEGF) production, and anti-apoptotic pathways. PA is widely recognized for its positive impact on overall health, including cognitive function and neuroplasticity.
The primary objective of this study is to evaluate the effects of IH and PA-administered individually, sequentially, or simultaneously-on cognitive performance and brain health in adults aged 50 to 65. The study will determine whether combining these interventions produces additive or synergistic benefits beyond those observed with each intervention alone. A total of approximately 176 participants will be enrolled and randomly assigned to one of five groups: (1) PA only, (2) IH only, (3) PA + IH sequentially, (4) PA + IH simultaneously, or (5) a control group receiving "placebo" hypoxia. Each participant will complete 18 sessions over a 6-week period (3 sessions per week), with sessions conducted in a hypoxic chamber at CIC 1402 and at the exercise testing facility of the University of Poitiers.
Outcome measures include comprehensive cognitive testing (global cognition, reaction time, executive function, and divided attention), assessments of autonomy (e.g., activities of daily living), and physiological parameters (e.g., SpO₂, cerebral oxygenation, heart rate, and blood pressure). Biomarker analysis will include brain-derived neurotrophic factor (BDNF), VEGF, irisin, and markers of HIF activation to elucidate the mechanisms underlying any observed improvements. Vascular function will be assessed using Doppler ultrasound and near-infrared spectroscopy (NIRS), and daily activity levels will be monitored with accelerometers.
Inclusion criteria require participants to be 50-65 years old, with a Montreal Cognitive Assessment (MoCA) score ≥24, no participation in other exercise interventions in the past 6 months, and no altitude exposure above 1,500 m in the preceding 3 months. Additional eligibility requirements include the absence of chronic kidney, cardiovascular, metabolic, neurological, or orthopedic disease, as well as no significant respiratory history. Exclusion criteria include active smoking, major cardiovascular complications within the last 3 months, severe hypertension, chronic respiratory insufficiency, diabetes, or any other condition that could compromise safety or study compliance. A qualified medical doctor will confirm eligibility during the inclusion process.
By evaluating different delivery methods of IH and PA, this research aims to identify the most effective, non-pharmacological approach to preserving-or potentially enhancing-cognitive function in middle-aged adults. Findings may contribute to targeted preventive strategies and novel therapeutic interventions, addressing the growing public health burden of age-related cognitive decline.
- Being tested
- Hypoxia, intermittent, physical exercise, Sham (No Treatment) hypoxia
- Keywords
- intermittent Hypoxia Training, Hypoxic Conditioning, Physical Activity, Exercise Intervention, Cognitive Function, Brain Health, Non-Pharmacological Interventions, Middle-Aged Adults, Healthy Aging, Cognitive Decline Prevention, Neuroplasticity
- Medical subject headings
- Motor Activity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypoxia, intermittentOther
Also called hypoxic expousre
Moderate-Intensity Aerobic Exercise (~60-70% of maximum heart rate) and Intermittent Hypoxia (maintained between 80-90% during hypoxic phases)
physical exerciseOther
Moderate-Intensity Aerobic Exercise (~60-70% of maximum heart rate)
Sham (No Treatment) hypoxiaOther
Exposure to normoxic air (FiO₂ ~20.9%) instead of actual hypoxia.
| Study group | Role | What they receive |
|---|---|---|
| Intermittent Hypoxia Only | Experimental | Participants in this arm will undergo a protocol of repeated cycles of hypoxia and normoxia. Each session will consist of alternating 5-minute hypoxic exposures with 5-minute normoxic intervals, for a total of approximately 30 minutes per session. Sessions will be held three times per week for six weeks (18 total sessions), and will be conducted at rest inside a hypoxic chamber under clinical supervision. Receives: Other: Hypoxia, intermittent |
| Physical exercise only | Experimental | Participants allocated to this arm will engage in a moderate-intensity aerobic exercise program (~60-70% of age-predicted maximum heart rate and based on a standardized scale of perceived exertion) three times per week for six weeks (total of 18 sessions). Each session will last approximately 30 minutes and may involve activities such as treadmill walking, cycling, or other forms of continuous aerobic exercise. The exercise intensity is monitored (e.g., via heart rate or perceived exertion) to ensure a moderate level of effort that is both safe and beneficial for overall cardiovascular and cognitive health. Receives: Other: physical exercise |
| Sequential Combination of Intermittent Hypoxia (IH) and Physical Activity (PA) | Experimental | Participants in this arm will undergo both Intermittent Hypoxia Training (IH) and Physical Activity (PA) within the same session, but in a sequential manner. The order of interventions (IH first or PA first) will be randomized to account for potential order effects. Each session consists of 30 minutes of IHT (5-minute hypoxia cycles, followed by 5-minute normoxic intervals, with SpO₂ maintained between 80% and 90%) and 30 minutes of moderate-intensity aerobic exercise (e.g., treadmill walking, cycling). Sessions will be held three times per week for six weeks (18 total sessions) and will be conducted under clinical supervision in a controlled environment. Receives: Other: Hypoxia, intermittent; Other: physical exercise |
| Simultaneous Combination of Intermittent Hypoxia (IH) and Physical Activity (PA) | Experimental | Participants in this arm will undergo Intermittent Hypoxia (IH) and Physical Activity (PA) simultaneously within the same session. During each session, participants will engage in moderate-intensity aerobic exercise (e.g., treadmill walking or cycling) while being exposed to IH. The total session duration will be 30 minutes, consisting of repeated cycles of 5 minutes of hypoxia followed by 5 minutes of normoxia, with SpO₂ maintained between 80% and 90% during hypoxic intervals. Sessions will be conducted three times per week for six weeks (18 total sessions) under clinical supervision in a controlled environment. Receives: Other: Hypoxia, intermittent; Other: physical exercise |
| Sham (Placebo) Intermittent Hypoxia | Placebo comparator | Participants in this arm will undergo a sham (placebo) version of Intermittent Hypoxia (IH), where they will be exposed to normoxic air (FiO₂ ~20.9%) instead of actual hypoxia. The session structure will mimic the IH protocol, alternating between 5-minute "hypoxia" periods and 5-minute normoxia periods for a total of 30 minutes per session, but without a real reduction in oxygen levels. Sessions will be held three times per week for six weeks (18 total sessions) and will be conducted at rest inside a hypoxic chamber under clinical supervision. Receives: Other: Sham (No Treatment) hypoxia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cognitive Function: Montreal Cognitive Assessment (MoCA)
1-Montreal Cognitive Assessment (MoCA)
- Score Range: 0 to 30
- Interpretation: Higher scores indicate better cognitive function.
Measured: Baseline (Week 0),Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cerebral Oxygenation - Tissue Saturation Index (TSI)
- Method: Near-Infrared Spectroscopy (NIRS)
- Measure: Tissue Saturation Index (TSI), expressed as a percentage (%)
- Interpretation: Higher TSI values indicate better cerebral oxygenation, reflecting efficient oxygen delivery and utilization in brain tissue.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Biomarker Analysis- Brain-Derived Neurotrophic Factor (BDNF) Levels
- Method: Enzyme-Linked Immunosorbent Assay (ELISA)
- Unit of Measure: pg/mL
- Interpretation: Higher BDNF levels indicate greater neuroplasticity, neuronal survival, and cognitive function support.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cerebral blood flow
Method: Transcranial Doppler (TCD) Measures: Mean, systolic, and diastolic blood flow velocities in cerebral arteries.
Interpretation: Higher flow velocities indicate increased cerebral perfusion, while reduced velocities may reflect impaired blood flow regulation or vascular resistance.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cognitive Function: Stroop Test
The Stroop Test is a widely used cognitive assessment tool designed to measure executive function, specifically selective attention, cognitive flexibility, and inhibitory control. It evaluates the ability to suppress automatic responses and manage conflicting information.
-Score Range: Reaction Time (measured in milliseconds, ms): Represents the time taken to respond in each condition.
Accuracy Percentage (%): Indicates the proportion of correct responses relative to total trials.
-Interpretation: Lower reaction times indicate faster cognitive processing and improved efficiency in managing conflicting information.
Higher accuracy percentages reflect better cognitive control, attentional capacity, and inhibitory function.
Performance in the incongruent condition is of particular interest, as it requires greater cognitive effort and executive control.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cognitive Function: N-Back
The N-Back Test is a cognitive task designed to assess working memory, attention, and cognitive flexibility. It requires participants to continuously monitor a sequence of stimuli (e.g., letters, numbers, or shapes) and determine whether the current stimulus matches one presented N steps earlier in the sequence. The task increases in difficulty as N increases, demanding greater mental effort to update and maintain information in working memory.
-Score Range: Accuracy Percentage (%): Proportion of correct responses over total trials. Reaction Time (ms): Time taken to respond to correct matches.
-Interpretation: Higher accuracy reflects better working memory capacity and attentional control.
Faster reaction times indicate efficient cognitive processing. Performance decline in higher N levels suggests increased cognitive load and reduced working memory capacity.
Deficits in accuracy or reaction time may indicate difficulties in executive function and attentional flexibility.
Measured: Baseline (Week 0),Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cognitive Function:Operation Span Test Task
The Operation Span (O-Span) Test is a cognitive task designed to assess working memory capacity and attentional control. It requires participants to simultaneously process and store information, challenging their ability to maintain and manipulate information while handling a secondary task.
The test includes:
Two training trials for familiarization. Six experimental trials, with letter sequences ranging from four to six letters.
-Score Range: Absolute Span Score: 0 to 12 (number of correctly recalled letter sequences).
Interpretation:
Higher scores indicate greater working memory capacity and better attentional control.
Lower scores may suggest difficulties in managing cognitive load and maintaining task-relevant information under distraction.
Performance reflects the ability to simultaneously process and store information, which is critical for complex cognitive tasks such as reasoning, problem-solving, and multitasking.
Measured: Baseline (Week 0),Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cognitive Function: The Trail Making Test
The Trail Making Test (TMT) is a widely used neuropsychological assessment designed to evaluate processing speed, cognitive flexibility, attention, and executive functioning.
It consists of two parts:
- TMT-A: Measures visual scanning, processing speed, and motor function. Participants connect numbers in ascending order (e.g., 1 → 2 → 3) as quickly as possible.
- TMT-B: Assesses cognitive flexibility and task-switching ability. Participants alternate between numbers and letters in sequential order (e.g., 1 → A → 2 → B → 3 → C).
- Score Range:
Outcome Measure: Time (in seconds) taken to complete each part. Higher scores (longer times) indicate slower processing speed and reduced cognitive flexibility.
-Interpretation: Lower scores (faster completion time) indicate better processing speed, visual attention, and cognitive flexibility.
Higher scores (longer completion time) may reflect impairments in executive function, attention, or visuomotor speed.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cerebral Oxygenation - Oxyhemoglobin (O₂Hb)
- Method: Near-Infrared Spectroscopy (NIRS)
- Measure: Oxyhemoglobin (O₂Hb), expressed in micromolar concentration (µM)
- Interpretation: Higher O₂Hb levels indicate greater oxygen availability and delivery to brain tissues.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cerebral Oxygenation - Deoxyhemoglobin (HHb)
- Method: Near-Infrared Spectroscopy (NIRS)
- Measure: Deoxyhemoglobin (HHb), expressed in micromolar concentration (µM)
- Interpretation: Elevated HHb levels may suggest reduced oxygen extraction or utilization, potentially indicating impaired cerebral oxygenation.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Cerebral Oxygenation - Total Hemoglobin (tHb)
- Method: Near-Infrared Spectroscopy (NIRS)
- Measure: Total Hemoglobin (tHb), expressed in micromolar concentration (µM)
- Interpretation: Higher tHb values reflect greater blood volume in cerebral tissue, which may indicate increased cerebral perfusion.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Biomarker Analysis-Vascular Endothelial Growth Factor (VEGF) Levels
- Method: Enzyme-Linked Immunosorbent Assay (ELISA)
- Unit of Measure: pg/mL
- Interpretation: Increased VEGF levels suggest enhanced angiogenesis, vascular function, and cerebral blood flow.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Biomarker Analysis -Irisin Levels
- Method: Enzyme-Linked Immunosorbent Assay (ELISA)
- Unit of Measure: ng/mL
- Interpretation: Higher irisin levels indicate improved metabolic regulation, muscle-derived neuroprotection, and brain function.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Biomarker Analysis-Hypoxia-Inducible Factor-1 Alpha (HIF-1α) Pathway Activation
- Method: Quantitative Polymerase Chain Reaction (qPCR) / Western Blot
- Unit of Measure: Relative expression level (fold change compared to baseline)
- Interpretation: Increased HIF-1α activation suggests enhanced cellular adaptation to hypoxia, improved metabolic regulation, and potential neuroprotection.
Measured: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Secondary outcomes (1)
Autonomy and Daily Functioning (Activities of Daily Living Scale)
- Full Name: Activities of Daily Living (ADL) Scale
- Description: This scale assesses an individual's ability to perform essential daily activities independently. It evaluates functions such as dressing, bathing, eating, mobility, toileting, and grooming.
- Score Range: 0 to 6
- Interpretation: A higher score indicates greater independence, while a lower score reflects higher dependency in daily functioning.
Measured: Baseline, and post-intervention (week 6, session 18)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2025
- Study start1 Apr 2025 (estimated)
- Primary completion30 Sep 2026 (estimated)
- Study completion30 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cognitive Ability, GeneralStudies 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
- This is a randomized, parallel-group trial
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 176 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ayoub Boulares
- Sponsor type
- University, hospital or other
- Collaborators
- University of Poitiers, Laboratory MOVE, Faculty of Sport Sciences, University of Poitiers, France
- Responsible party
- Sponsor-investigator, Ayoub Boulares, University of Poitiers
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06874387
- Sponsor's protocol ID
- HYPOX-AGE-2024-A00894-43
- Acronym
- HYPOX-AGE
- Status last verified
- Mar 2025
- First submitted
- 25 Feb 2025
- Last updated
- 13 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Schega L, Peter B, Brigadski T, Lessmann V, Isermann B, Hamacher D, Torpel A. Effect of intermittent normobaric hypoxia on aerobic capacity and cognitive function in older people. J Sci Med Sport. 2016 Nov;19(11):941-945. doi: 10.1016/j.jsams.2016.02.012. Epub 2016 Apr 26.
PubMed 27134133Boulares A, Pichon A, Faucher C, Bragazzi NL, Dupuy O. Effects of Intermittent Hypoxia Protocols on Cognitive Performance and Brain Health in Older Adults Across Cognitive States: A Systematic Literature Review. J Alzheimers Dis. 2024;101(1):13-30. doi: 10.3233/JAD-240711.
PubMed 39093075Schega L, Peter B, Torpel A, Mutschler H, Isermann B, Hamacher D. Effects of intermittent hypoxia on cognitive performance and quality of life in elderly adults: a pilot study. Gerontology. 2013;59(4):316-23. doi: 10.1159/000350927. Epub 2013 May 3.
PubMed 23652274
Study at a glance
From the registry record, last updated by the sponsor on 13 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Towards a Better Understanding of the Combination of Intermittent Hypoxia and Physical Exercise: Comparison of Effects on Cognitive and Cerebral Capacities in Middle-Aged Adults
- ClinicalTrials.gov ID
- NCT06874387
- Acronym / sponsor ID
- HYPOX-AGE / HYPOX-AGE-2024-A00894-43
- Keywords
- intermittent Hypoxia Training, Hypoxic Conditioning, Physical Activity, Exercise Intervention, Cognitive Function, Brain Health, Non-Pharmacological Interventions, Middle-Aged Adults
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 176 participants (estimated)
- Lead sponsor
- Ayoub BoularesUniversity, hospital or other
- Collaborators
- University of Poitiers, Laboratory MOVE, Faculty of Sport Sciences, University of Poitiers, France
- Study start
- 1 Apr 2025 (estimated)
- Primary completion
- 30 Sep 2026 (estimated)
- Study completion
- 30 Dec 2026 (estimated)
- First posted
- 13 Mar 2025 (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.
This study investigates whether intermittent hypoxia (IH) and physical activity (PA), either alone or in combination (simultaneously or sequentially), can improve cognitive function and brain health in middle-aged adults (50-65 years old). The hypothesis is that (1) each intervention alone (IHT or PA) provides cognitive benefits and (2) combining IHT with PA may yield additive or synergistic effects, particularly when administered simultaneously rather than sequentially. By comparing these distinct interventions, the study aims to determine which approach best preserves or enhances cognitive performance in middle-aged adults. Findings from this research may inform non-pharmacological strategies to promote healthy aging and reduce the risk of age-related cognitive decline.
Detailed description
Rapid demographic aging worldwide is driving a surge in age-related conditions, including neurodegenerative diseases and cognitive disorders. Projections estimate that the number of people living with dementia could reach 78 million by 2030 and 139 million by 2050, underscoring the urgent need for effective, non-pharmacological strategies to preserve brain health. Intermittent hypoxia (IH) and physical activity (PA) are two promising interventions that may help prevent or mitigate cognitive decline. IH-an approach involving repeated cycles of reduced oxygen (11-16% FiO₂) followed by normoxic recovery-has shown benefits across diverse health domains (cardiovascular, metabolic, respiratory, and neurological), potentially through mechanisms such as the activation of Hypoxia-Inducible Factor (HIF), enhanced vascular endothelial growth factor (VEGF) production, and anti-apoptotic pathways. PA is widely recognized for its positive impact on overall health, including cognitive function and neuroplasticity.
The primary objective of this study is to evaluate the effects of IH and PA-administered individually, sequentially, or simultaneously-on cognitive performance and brain health in adults aged 50 to 65. The study will determine whether combining these interventions produces additive or synergistic benefits beyond those observed with each intervention alone. A total of approximately 176 participants will be enrolled and randomly assigned to one of five groups: (1) PA only, (2) IH only, (3) PA + IH sequentially, (4) PA + IH simultaneously, or (5) a control group receiving "placebo" hypoxia. Each participant will complete 18 sessions over a 6-week period (3 sessions per week), with sessions conducted in a hypoxic chamber at CIC 1402 and at the exercise testing facility of the University of Poitiers.
Outcome measures include comprehensive cognitive testing (global cognition, reaction time, executive function, and divided attention), assessments of autonomy (e.g., activities of daily living), and physiological parameters (e.g., SpO₂, cerebral oxygenation, heart rate, and blood pressure). Biomarker analysis will include brain-derived neurotrophic factor (BDNF), VEGF, irisin, and markers of HIF activation to elucidate the mechanisms underlying any observed improvements. Vascular function will be assessed using Doppler ultrasound and near-infrared spectroscopy (NIRS), and daily activity levels will be monitored with accelerometers.
Inclusion criteria require participants to be 50-65 years old, with a Montreal Cognitive Assessment (MoCA) score ≥24, no participation in other exercise interventions in the past 6 months, and no altitude exposure above 1,500 m in the preceding 3 months. Additional eligibility requirements include the absence of chronic kidney, cardiovascular, metabolic, neurological, or orthopedic disease, as well as no significant respiratory history. Exclusion criteria include active smoking, major cardiovascular complications within the last 3 months, severe hypertension, chronic respiratory insufficiency, diabetes, or any other condition that could compromise safety or study compliance. A qualified medical doctor will confirm eligibility during the inclusion process.
By evaluating different delivery methods of IH and PA, this research aims to identify the most effective, non-pharmacological approach to preserving-or potentially enhancing-cognitive function in middle-aged adults. Findings may contribute to targeted preventive strategies and novel therapeutic interventions, addressing the growing public health burden of age-related cognitive decline.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 5
- Model description
- This is a randomized, parallel-group trial
| Arm | Type | Receives |
|---|---|---|
| Intermittent Hypoxia Only | Experimental | Other: Hypoxia, intermittentParticipants in this arm will undergo a protocol of repeated cycles of hypoxia and normoxia. Each session will consist of alternating 5-minute hypoxic exposures with 5-minute normoxic intervals, for a total of approximately 30 minutes per session. Sessions will be held three times per week for six weeks (18 total sessions), and will be conducted at rest inside a hypoxic chamber under clinical supervision. |
| Physical exercise only | Experimental | Other: physical exerciseParticipants allocated to this arm will engage in a moderate-intensity aerobic exercise program (~60-70% of age-predicted maximum heart rate and based on a standardized scale of perceived exertion) three times per week for six weeks (total of 18 sessions). Each session will last approximately 30 minutes and may involve activities such as treadmill walking, cycling, or other forms of continuous aerobic exercise. The exercise intensity is monitored (e.g., via heart rate or perceived exertion) to ensure a moderate level of effort that is both safe and beneficial for overall cardiovascular and cognitive health. |
| Sequential Combination of Intermittent Hypoxia (IH) and Physical Activity (PA) | Experimental | Other: Hypoxia, intermittent, Other: physical exerciseParticipants in this arm will undergo both Intermittent Hypoxia Training (IH) and Physical Activity (PA) within the same session, but in a sequential manner. The order of interventions (IH first or PA first) will be randomized to account for potential order effects. Each session consists of 30 minutes of IHT (5-minute hypoxia cycles, followed by 5-minute normoxic intervals, with SpO₂ maintained between 80% and 90%) and 30 minutes of moderate-intensity aerobic exercise (e.g., treadmill walking, cycling). Sessions will be held three times per week for six weeks (18 total sessions) and will be conducted under clinical supervision in a controlled environment. |
| Simultaneous Combination of Intermittent Hypoxia (IH) and Physical Activity (PA) | Experimental | Other: Hypoxia, intermittent, Other: physical exerciseParticipants in this arm will undergo Intermittent Hypoxia (IH) and Physical Activity (PA) simultaneously within the same session. During each session, participants will engage in moderate-intensity aerobic exercise (e.g., treadmill walking or cycling) while being exposed to IH. The total session duration will be 30 minutes, consisting of repeated cycles of 5 minutes of hypoxia followed by 5 minutes of normoxia, with SpO₂ maintained between 80% and 90% during hypoxic intervals. Sessions will be conducted three times per week for six weeks (18 total sessions) under clinical supervision in a controlled environment. |
| Sham (Placebo) Intermittent Hypoxia | Placebo comparator | Other: Sham (No Treatment) hypoxiaParticipants in this arm will undergo a sham (placebo) version of Intermittent Hypoxia (IH), where they will be exposed to normoxic air (FiO₂ ~20.9%) instead of actual hypoxia. The session structure will mimic the IH protocol, alternating between 5-minute "hypoxia" periods and 5-minute normoxia periods for a total of 30 minutes per session, but without a real reduction in oxygen levels. Sessions will be held three times per week for six weeks (18 total sessions) and will be conducted at rest inside a hypoxic chamber under clinical supervision. |
Who may qualify
- Ages
- 50 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
Key exclusion criteria (12 listed)
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 |
|---|---|---|
| Hypoxia, intermittentAlso: hypoxic expousreModerate-Intensity Aerobic Exercise (~60-70% of maximum heart rate) and Intermittent Hypoxia (maintained between 80-90% during hypoxic phases) | Other | Intermittent Hypoxia Only, Sequential Combination of Intermittent Hypoxia (IH) and Physical Activity (PA), Simultaneous Combination of Intermittent Hypoxia (IH) and Physical Activity (PA) |
| physical exerciseModerate-Intensity Aerobic Exercise (~60-70% of maximum heart rate) | Other | Physical exercise only, Sequential Combination of Intermittent Hypoxia (IH) and Physical Activity (PA), Simultaneous Combination of Intermittent Hypoxia (IH) and Physical Activity (PA) |
| Sham (No Treatment) hypoxiaExposure to normoxic air (FiO₂ ~20.9%) instead of actual hypoxia. | Other | Sham (Placebo) Intermittent Hypoxia |
Primary outcome
Cognitive Function: Montreal Cognitive Assessment (MoCA)
Time frame: Baseline (Week 0),Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
1-Montreal Cognitive Assessment (MoCA) * Score Range: 0 to 30 * Interpretation: Higher scores indicate better cognitive function.
Cerebral Oxygenation - Tissue Saturation Index (TSI)
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Near-Infrared Spectroscopy (NIRS) * Measure: Tissue Saturation Index (TSI), expressed as a percentage (%) * Interpretation: Higher TSI values indicate better cerebral oxygenation, reflecting efficient oxygen delivery and utilization in brain tissue.
Biomarker Analysis- Brain-Derived Neurotrophic Factor (BDNF) Levels
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Enzyme-Linked Immunosorbent Assay (ELISA) * Unit of Measure: pg/mL * Interpretation: Higher BDNF levels indicate greater neuroplasticity, neuronal survival, and cognitive function support.
Cerebral blood flow
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
Method: Transcranial Doppler (TCD) Measures: Mean, systolic, and diastolic blood flow velocities in cerebral arteries. Interpretation: Higher flow velocities indicate increased cerebral perfusion, while reduced velocities may reflect impaired blood flow regulation or vascular resistance.
Cognitive Function: Stroop Test
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
The Stroop Test is a widely used cognitive assessment tool designed to measure executive function, specifically selective attention, cognitive flexibility, and inhibitory control. It evaluates the ability to suppress automatic responses and manage conflicting information. -Score Range: Reaction Time (measured in milliseconds, ms): Represents the time taken to respond in each condition. Accuracy Percentage (%): Indicates the proportion of correct responses relative to total trials. -Interpretation: Lower reaction times indicate faster cognitive processing and improved efficiency in managing conflicting information. Higher accuracy percentages reflect better cognitive control, attentional capacity, and inhibitory function. Performance in the incongruent condition is of particular interest, as it requires greater cognitive effort and executive control.
Cognitive Function: N-Back
Time frame: Baseline (Week 0),Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
The N-Back Test is a cognitive task designed to assess working memory, attention, and cognitive flexibility. It requires participants to continuously monitor a sequence of stimuli (e.g., letters, numbers, or shapes) and determine whether the current stimulus matches one presented N steps earlier in the sequence. The task increases in difficulty as N increases, demanding greater mental effort to update and maintain information in working memory. -Score Range: Accuracy Percentage (%): Proportion of correct responses over total trials. Reaction Time (ms): Time taken to respond to correct matches. -Interpretation: Higher accuracy reflects better working memory capacity and attentional control. Faster reaction times indicate efficient cognitive processing. Performance decline in higher N levels suggests increased cognitive load and reduced working memory capacity. Deficits in accuracy or reaction time may indicate difficulties in executive function and attentional flexibility.
Cognitive Function:Operation Span Test Task
Time frame: Baseline (Week 0),Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
The Operation Span (O-Span) Test is a cognitive task designed to assess working memory capacity and attentional control. It requires participants to simultaneously process and store information, challenging their ability to maintain and manipulate information while handling a secondary task. The test includes: Two training trials for familiarization. Six experimental trials, with letter sequences ranging from four to six letters. -Score Range: Absolute Span Score: 0 to 12 (number of correctly recalled letter sequences). Interpretation: Higher scores indicate greater working memory capacity and better attentional control. Lower scores may suggest difficulties in managing cognitive load and maintaining task-relevant information under distraction. Performance reflects the ability to simultaneously process and store information, which is critical for complex cognitive tasks such as reasoning, problem-solving, and multitasking.
Cognitive Function: The Trail Making Test
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
The Trail Making Test (TMT) is a widely used neuropsychological assessment designed to evaluate processing speed, cognitive flexibility, attention, and executive functioning. It consists of two parts: * TMT-A: Measures visual scanning, processing speed, and motor function. Participants connect numbers in ascending order (e.g., 1 → 2 → 3) as quickly as possible. * TMT-B: Assesses cognitive flexibility and task-switching ability. Participants alternate between numbers and letters in sequential order (e.g., 1 → A → 2 → B → 3 → C). * Score Range: Outcome Measure: Time (in seconds) taken to complete each part. Higher scores (longer times) indicate slower processing speed and reduced cognitive flexibility. -Interpretation: Lower scores (faster completion time) indicate better processing speed, visual attention, and cognitive flexibility. Higher scores (longer completion time) may reflect impairments in executive function, attention, or visuomotor speed.
Cerebral Oxygenation - Oxyhemoglobin (O₂Hb)
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Near-Infrared Spectroscopy (NIRS) * Measure: Oxyhemoglobin (O₂Hb), expressed in micromolar concentration (µM) * Interpretation: Higher O₂Hb levels indicate greater oxygen availability and delivery to brain tissues.
Cerebral Oxygenation - Deoxyhemoglobin (HHb)
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Near-Infrared Spectroscopy (NIRS) * Measure: Deoxyhemoglobin (HHb), expressed in micromolar concentration (µM) * Interpretation: Elevated HHb levels may suggest reduced oxygen extraction or utilization, potentially indicating impaired cerebral oxygenation.
Cerebral Oxygenation - Total Hemoglobin (tHb)
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Near-Infrared Spectroscopy (NIRS) * Measure: Total Hemoglobin (tHb), expressed in micromolar concentration (µM) * Interpretation: Higher tHb values reflect greater blood volume in cerebral tissue, which may indicate increased cerebral perfusion.
Biomarker Analysis-Vascular Endothelial Growth Factor (VEGF) Levels
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Enzyme-Linked Immunosorbent Assay (ELISA) * Unit of Measure: pg/mL * Interpretation: Increased VEGF levels suggest enhanced angiogenesis, vascular function, and cerebral blood flow.
Biomarker Analysis -Irisin Levels
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Enzyme-Linked Immunosorbent Assay (ELISA) * Unit of Measure: ng/mL * Interpretation: Higher irisin levels indicate improved metabolic regulation, muscle-derived neuroprotection, and brain function.
Biomarker Analysis-Hypoxia-Inducible Factor-1 Alpha (HIF-1α) Pathway Activation
Time frame: Baseline (Week 0), Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)
* Method: Quantitative Polymerase Chain Reaction (qPCR) / Western Blot * Unit of Measure: Relative expression level (fold change compared to baseline) * Interpretation: Increased HIF-1α activation suggests enhanced cellular adaptation to hypoxia, improved metabolic regulation, and potential neuroprotection.
1 secondary outcome
Autonomy and Daily Functioning (Activities of Daily Living Scale)
Time frame: Baseline, and post-intervention (week 6, session 18)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Mar 2025.
- Results publication: PubMed 27134133Schega L, Peter B, Brigadski T, Lessmann V, Isermann B, Hamacher D, Torpel A. Effect of intermittent normobaric hypoxia on aerobic capacity and cognitive function in older people. J Sci Med Sport. 2016 Nov;19(11):941-945. doi: 10.1016/j.jsams.2016.02.012. Epub 2016 Apr 26.
- Results publication: PubMed 39093075Boulares A, Pichon A, Faucher C, Bragazzi NL, Dupuy O. Effects of Intermittent Hypoxia Protocols on Cognitive Performance and Brain Health in Older Adults Across Cognitive States: A Systematic Literature Review. J Alzheimers Dis. 2024;101(1):13-30. doi: 10.3233/JAD-240711.
- Results publication: PubMed 23652274Schega L, Peter B, Torpel A, Mutschler H, Isermann B, Hamacher D. Effects of intermittent hypoxia on cognitive performance and quality of life in elderly adults: a pilot study. Gerontology. 2013;59(4):316-23. doi: 10.1159/000350927. Epub 2013 May 3.
- 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.
Questions about this trial
What is this clinical trial studying?
A study testing Hypoxia, intermittent and physical exercise in people with Cognitive Ability, General and Brain Health, run by Ayoub Boulares.
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 12 inclusion and 12 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: opening soon, as of the sponsor's last update on 13 Mar 2025. Status can change between updates, so confirm with the study contact before making plans.
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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Aurélien PICHIN, Professor (+33 6 82 95 19 70, aurelien.pichon@univ-poitiers.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cognitive Function: Montreal Cognitive Assessment (MoCA) (time frame: Baseline (Week 0),Week 1 (after 3 sessions), Week 6 (post-intervention, after session 18)). The study lists 14 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 NCT06874387, which also lists 3 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 13 Mar 2025.