Stroke, IschemicPhase 1/2PLASTIHCNCT05210088
PLAsticity, Security and Tolerance to Intermittent Hypoxic Conditioning Following Stroke
A Phase 1/2 study testing Hypoxia, intermittent and Normoxia in people with Stroke, Ischemic and Stroke Sequelae, run by University Hospital, Grenoble at 1 site in France.
Trial summary
By inducing endogenous neuroprotection, hypoxic post-conditioning following stroke may represent a harmless and efficient non-pharmacological innovative neuro-therapeutic modality aiming at inducing neuroplasticity and brain repair, as supported by many preclinical studies. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Stroke, Ischemic, Stroke Sequelae
- What is being tested?
- Hypoxia, intermittent and Normoxia
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 0 participants
- Where
- 1 siteFrance
- Study dates
- 1 Jan 2024to 1 Jan 2024
- Phase
- Phase 1/2
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients with minor cerebral infarction with NIHSS < or equal to 5 will be included in the protocol;
- Cerebral infarction occurring one month (±1 week) before the planned start of hypoxic exposure;
- Age ≥18 years;
- A first, unilateral, ischemic, supra-tentorial hemispheric stroke, confirmed by magnetic resonance imaging;
- Modified Rankin Scale score between 1 and 3, defining mild to moderate residual functional disability.
- A person affiliated with the social security system or benefits from such a system;
- A person who has given written informed consent.
Who cannot join
- Patients who are minors or over 85 years of age, pregnant or breastfeeding women, or women of childbearing potential in the absence of highly effective contraception;
- Stroke of the brainstem or cerebellum ;
- Severe aphasia, limiting the ability to understand the protocol;
- History of central or peripheral neurological pathology;
- Modified Rankin Scale score >0 before stroke;
- Known severe untreated obstructive sleep apnea syndrome, defined as an apnea-hypopnea index ≥ 30 events per hour of sleep;
Show all 17Show fewer
- Pre-existing hypoxemic lung disease (such as chronic obstructive pulmonary disease);
- Heart failure, defined as an ejection fraction ≤40% ;
- History of high altitude pathology;
- Scheduled stay at altitude (> 2500 m) during the study period ;
- Migraine;
- History of rheumatological or orthopedic disease of the lower limbs, amputation of the lower limb.
- Contraindication to magnetic resonance imaging;
- Subjects who cannot be contacted in an emergency;
- Subject in exclusion period of another study;
- Subject under administrative or judicial supervision;
- Persons referred to in Articles L1121-5 to L1121-8 of the "Code de la Santé Publique" (corresponds to all protected persons: pregnant women, women in labor, nursing mothers, persons deprived of their liberty by judicial or administrative decision, persons subject to a legal protection measure).
Trial locations and contacts
1 site in 1 country.
France1 site
Grenoble Aalpes University Hospital
Grenoble, Veuillez Sélectionner Une Région., 38000
About this study
By inducing endogenous neuroprotection, hypoxic post-conditioning following stroke may represent a harmless and efficient non-pharmacological innovative neuro-therapeutic modality aiming at inducing neuroplasticity and brain repair, as supported by many preclinical studies.
The investigators thus hypothesize that hypoxic post-conditioning represents a safe therapeutic strategy post-stroke. The investigators further hypothesize that hypoxic conditioning could enhance neuroplasticity and function in combination with conventional rehabilitative care.
Read more
The primary study endpoint will be safety. Safety will be assessed through the clinical review of the adverse events over the duration of the study, every 48 hours by a trained evaluator, blinded for the therapeutic intervention.
The investigators will further investigate the potential functional benefits of such a therapeutic approach on motor function, gait, balance, and cognition. The neurophysiological substrates of hypoxic conditioning-triggered neuroplasticity at a subacute delay post-stroke will also be investigated, based on biological and imagery markers.
Read the detailed description
Stroke is the second leading cause of death and the third leading cause of disability-adjusted life-years worldwide. If acute stroke therapy has decreased mortality, more than 50% of stroke survivors are left with sensorimotor and cognitive deficiencies. Recovery and rehabilitation treatments, aiming at inducing neuroplasticity, maximizing function in unaffected brain areas or implementing compensatory strategies to improve overall function, benefit from an extensive time window that ranges from days to months. Their development is urgently needed.
Several endogenous neuroprotective mechanisms are spontaneously engaged following stroke to achieve neuroprotection and stimulate brain repairing processes. Conditioning the central nervous system can trigger endogenous mechanisms of neuroprotection. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism. While hypoxia is well recognized as a common underlying mechanism of many pathological conditions, experimental data indicate that exposure to specific doses of hypoxia (by breathing a hypoxic gas mixture) can be neuroprotective.
Preconditioning is defined as the exposure to the conditioning stimulus before injury onset, to induce tolerance or resistance to the subsequent injury. Postconditioning refers to the application of the conditioning stimulus after injury or damage, to stimulate tissue reparation or neuroplasticity. As stroke is an unpredictable event, translating hypoxic preconditioning to clinical practice seems difficult. However, developing postconditioning strategies seems of clinical and rehabilitative relevance. Thus, an increase in neuronal salvage and neurogenesis, along with an increase in brain-derived neurotrophic factor expression and a reduced neuroinflammation were shown in murine models of hypoxic conditioning following ischemic stroke.
By inducing endogenous neuroprotection, hypoxic conditioning may represent a harmless and efficient non-pharmacological innovative neuro-therapeutic modality aiming at inducing neuroplasticity and brain repair, as supported by many preclinical studies.
The main working hypothesis is that hypoxic postconditioning may represent a safe therapeutic strategy post-stroke.
The investigators further hypothesize that hypoxic conditioning could enhance neuroplasticity and function in combination with conventional rehabilitative care.
The primary study endpoint will be safety. Safety will be assessed through the clinical review of the adverse events over the duration of the study, every 48 hours by a trained evaluator, blinded for the therapeutic intervention.
All adverse events will be evaluated and quoted in accordance with National Institute of Health Common Criteria for Terminology for Adverse Events 5.0 (NIH CCTAE) recommendations, particularly with respect to Sub-sections "Cardiac disorders ", "Nervous system disorders" and "Vascular Disorders". Safety assessments will be performed every 48 hours, throughout the 8-week conditioning period, in addition to the conventional clinical follow-up performed in the rehabilitation unit.
The potential functional benefits of such a therapeutic approach on motor function, gait, balance, and cognition will also be further investigated. The neurophysiological substrates of hypoxic conditioning-triggered neuroplasticity at a subacute delay post-stroke will be investigated, based on biological (serum inflammatory markers, growth and neurogenesis biomarkers) and imagery markers (morphological MRI sequences, functional connectivity (resting state), and brain vascularization).
- Conditions
- Stroke, Ischemic, Stroke Sequelae
- Being tested
- Hypoxia, intermittent, Normoxia
- Keywords
- Stroke, Hypoxic conditioning, Intermittent hypoxia, Recovery, Biomarkers, Safety
- Medical subject headings
- Ischemic Stroke, Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Hypoxia, intermittentDrug
Also called Hypoxic conditioning, Hypoxia
The device used to generate the intermittent hypoxia stimulus is a gas mixer used in current clinical practice and research (Altitrainer®, SMTEC S.A. Switzerland). The hypoxic stimulus will be obtained by having the subject inhale a gas mixture enriched in nitrogen by means of a mask, in variable proportion according to the desired degree of hypoxia.
Hypoxic conditioning will be performed in three one-hour sessions per week, performed non-consecutively, for 8 weeks. The hypoxic stimulus will be intermittent, and each session will consist of 7 cycles of 5 minutes of hypoxia alternating with 3 minutes of normoxia (FiO2 = 21%). The subjects will be installed in a semi-recumbent position, at rest in a quiet environment.
For hypoxic exposure, the inspired fraction of oxygen (FiO2) will be set individually to achieve the targeted level of desaturation (Pulse Oxygen Saturation, SpO2) continuously monitored.
NormoxiaOther
The normoxic stimulus will be obtained by having the subjects inhale via a face mask a normoxic gas mixture with a fixed FiO2 of 21%, delivered by the gas mixing device (Altitrainer®, SMTEC S.A. Switzerland).
| Study group | Role | What they receive |
|---|---|---|
| PHASE 1- Dose escalation protocol | Experimental | 4-step dose-escalation protocol with increasing doses of intermittent hypoxia and continuous reassessment of safety criteria (primary endpoint).
Hypoxic conditioning will be performed in three one-hour sessions per week, performed non-consecutively, for 8 weeks. The hypoxic stimulus will be intermittent, and each session will consist of 7 cycles of 5 minutes of hypoxia alternating with 3 minutes of normoxia (FiO2 = 21%). The subjects will be installed in a semi-recumbent position, at rest in a quiet environment.
For hypoxic exposure, the inspired fraction of oxygen (FiO2) will be set individually to achieve the targeted level of desaturation (Pulse Oxygen Saturation, SpO2) continuously monitored: 90% for stage 1 (n=1 patient), 85% for stage 2 (n=3 patients), 80% for stage 3 (n=3 patients), 75% for stage 4 (n=3 patients). Receives: Drug: Hypoxia, intermittent |
| PHASE 2 - Intermittent hypoxia group | Active comparator | Group exposed to an intermittent hypoxic stimulus (n=20, target pulsed saturation in dioxygen 75%).
The device used is a gas mixer already in use in the unit and used in current clinical practice and research in our team (Altitrainer®, Sport and Medical TEChnologies S.A. (SMTEC S.A.), Switzerland). The hypoxic stimulus will be obtained by having the subject inhale a gas mixture enriched in nitrogen by means of a mask, in variable proportion according to the desired degree of hypoxia.
Hypoxic conditioning will be performed in three one-hour sessions per week, performed non-consecutively, for 8 weeks. The hypoxic stimulus will be intermittent, and each session will consist of 7 cycles of 5 minutes of hypoxia alternating with 3 minutes of normoxia (FiO2 = 21%). The subjects will be installed in a semi-recumbent position, at rest in a quiet environment.
For hypoxic exposure, the FiO2 will be set individually to achieve the targeted level of desaturation. Receives: Drug: Hypoxia, intermittent |
| PHASE 2 - Sham (Normoxia) group | Sham comparator | Normoxia group (n=10, FiO2 = 21%). The same setting will be used as in the Intermittent hypoxia group, but subjects will breathe ambient air throughout the conditioning procedure. Receives: Other: Normoxia |
What is being measured
The primary outcome is the main question the study is designed to answer.
Secondary adverse events
The safety of such a therapeutic strategy will be assessed by systematic screening for adverse events at each conditioning session and at follow-up visits throughout the duration of exposure (8 weeks) by a trained experimenter, blinded to the therapeutic intervention.
All adverse events will be assessed and scored as a composite endpoint according to the NIH CCTAE 5.0 (National Institute of Health Common Terminology Criteria for Adverse Events), including in particular those listed in the sub-sections on "Cardiological Pathologies", "Central Nervous System Pathologies" and "Vascular Pathologies".
Measured: Through study completion, an average of 8 weeks
Secondary outcomes (14)
Fugl-Meyer
Function - Fugl-Meyer motor function Score range: 0-100 Higher values indicate better performance. A score of 96-99 indicates light motor incoordination A score of 85-95 indicates hemiparesis A score ≤ 84 indicates hemiplegia
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
New Functional ambulation category (nFAC) score
Function - New Functional ambulation category (nFAC) score Score range: 0-5 A score of 0 indicates no functional ability to walk A score of 5 indicates independent walking
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Prospective collection of number of falls
Function - Prospective collection of number of falls
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Modified Rankin Scale (mRS)
Activity limitation - Modified Rankin Scale (mRS) Score range: 0-6 The mRS scores range from à (no symptom) to 6 (death)
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Barthel index
Activity limitation - Barthel index Score range: 0-100 The higher the score, the better the function and the independence
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
16-item Stroke Impact Scale
Participation The higher the score, the better the performance.
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
10-metre walk test
Mobility - Instrumented 10-metre walk test, carried out at spontaneous walking speed, 3 trials: collection of quantitative spatiotemporal step parameters and their variability, collection of walking speed.
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Timed-up and Go test
Mobility - Timed-up and Go test: 3 trials
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Montreal Cognitive Assessment
Neuropsychological assessment Score range: 0-30 Normal if >26/30 The higher the score, the better the cognitive performance.
Measured: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Morphological sequences
The acquisitions will be performed on a 3 Tesla magnetic resonance imaging (MRI) machine.
High-resolution anatomical sequences: T1, T2, FLAIR, for calculation of lesion volume and delineation of lesion mask.
Measured: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Diffusion and perfusion sequences
The acquisitions will be performed on a 3 Tesla magnetic resonance imaging (MRI) machine.
Bolus perfusion (gadolinium) T1 and Diffusion Tensor Imaging (DTI, 60 directions or High Angular Resolution Diffusion Imaging (HARDI)), allowing calculation of the Apparent Diffusion Coefficient (ADC) map.
Measured: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Cerebral blood flow
The acquisitions will be performed on a 3 Tesla magnetic resonance imaging (MRI) machine.
Cerebral vasoreactivity (to a hypercapnic stimulus) assessed by Arterial Spin Labelling (ASL) and Blood oxygenation level-dependent (BOLD) sequences.
Measured: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Resting state functional magnetic resonance imaging (fMRI)
The acquisitions will be performed on a 3 Tesla magnetic resonance imaging (MRI) machine.
Functional connectivity measurements.
Measured: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Cerebral Blood Flow
Cerebral blood flow will be assessed by measuring the flow velocity in the middle cerebral artery (MCAv), estimated by continuous measurement of the right middle cerebral artery using a 2 megahertz (MHz) pulsed transcranial Doppler (TCD) (MultiDop T, Compumedics Germany GmbH, Germany). Following standardized research techniques, the Doppler probe will be fixed to the temporal window with the aid of a helmet (DiaMon, Compumedics Germany GmbH) to maintain an optimal insonation position throughout the study and thus avoid any movement artifact.
Measured: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jan 2022
- Study start1 Jan 2024
- Primary completion1 Jan 2024
- Study completion1 Jan 2024
Why it stopped: faisability
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 Stroke, IschemicStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe 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 1/2
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- Phase I (safety and tolerability) clinical trial (impact on intermediate endpoints) evaluating a chronic (one month) hypoxic conditioning strategy for stroke, single-center, dose-escalation accelerated titration design (Liu S., Contemp. Clin. Trials. 2013) with continuous safety reassessment method. Dose escalation protocol. Dose escalation consisting of 4 successive steps, with increasing doses of hypoxia and continuous reassessment of safety criteria (primary endpoint, see below) Phase 2: Randomised, double-blind, controlled study comparing a group exposed to intermittent hypoxic post-conditioning versus a group exposed for the same duration and under the same conditions to a normoxic stimulus.
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Collaborators
- Agir pour les maladies chroniques
- Responsible party
- Sponsor
- Investigators
- Sébastien BAI, MD PHD, Principal investigator, CHU Grenoble Alpes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05210088
- Sponsor's protocol ID
- 2021-A00104-37
- Acronym
- PLASTIHC
- Status last verified
- Jun 2024
- First submitted
- 5 Oct 2021
- Last updated
- 4 Jun 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data collected for the study, including deidentified individual participant data will be made available to others following the publication of this article, for academic purposes (e.g., meta-analyses) on request to the principal investigator, after the publication of the results of the present study.
Publications
Verges S, Chacaroun S, Godin-Ribuot D, Baillieul S. Hypoxic Conditioning as a New Therapeutic Modality. Front Pediatr. 2015 Jun 22;3:58. doi: 10.3389/fped.2015.00058. eCollection 2015.
PubMed 26157787Baillieul S, Chacaroun S, Doutreleau S, Detante O, Pepin JL, Verges S. Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries? Exp Biol Med (Maywood). 2017 Jun;242(11):1198-1206. doi: 10.1177/1535370217712691.
PubMed 28585890Burtscher J, Syed MMK, Lashuel HA, Millet GP. Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease? Mov Disord. 2021 Apr;36(4):857-861. doi: 10.1002/mds.28544. Epub 2021 Feb 27.
PubMed 33638916
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PLAsticity, Security and Tolerance to Intermittent Hypoxic Conditioning Following Stroke
- ClinicalTrials.gov ID
- NCT05210088
- Acronym / sponsor ID
- PLASTIHC / 2021-A00104-37
- Conditions
- Stroke, Ischemic, Stroke Sequelae
- Keywords
- Stroke, Hypoxic conditioning, Intermittent hypoxia, Recovery, Biomarkers, Safety
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: faisability
- Enrolment
- 0 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- Agir pour les maladies chroniques
- Study start
- 1 Jan 2024 (actual)
- Primary completion
- 1 Jan 2024 (actual)
- Study completion
- 1 Jan 2024 (actual)
- First posted
- 27 Jan 2022 (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.
By inducing endogenous neuroprotection, hypoxic post-conditioning following stroke may represent a harmless and efficient non-pharmacological innovative neuro-therapeutic modality aiming at inducing neuroplasticity and brain repair, as supported by many preclinical studies.
The investigators thus hypothesize that hypoxic post-conditioning represents a safe therapeutic strategy post-stroke. The investigators further hypothesize that hypoxic conditioning could enhance neuroplasticity and function in combination with conventional rehabilitative care.
The primary study endpoint will be safety. Safety will be assessed through the clinical review of the adverse events over the duration of the study, every 48 hours by a trained evaluator, blinded for the therapeutic intervention.
The investigators will further investigate the potential functional benefits of such a therapeutic approach on motor function, gait, balance, and cognition. The neurophysiological substrates of hypoxic conditioning-triggered neuroplasticity at a subacute delay post-stroke will also be investigated, based on biological and imagery markers.
Detailed description
Stroke is the second leading cause of death and the third leading cause of disability-adjusted life-years worldwide. If acute stroke therapy has decreased mortality, more than 50% of stroke survivors are left with sensorimotor and cognitive deficiencies. Recovery and rehabilitation treatments, aiming at inducing neuroplasticity, maximizing function in unaffected brain areas or implementing compensatory strategies to improve overall function, benefit from an extensive time window that ranges from days to months. Their development is urgently needed.
Several endogenous neuroprotective mechanisms are spontaneously engaged following stroke to achieve neuroprotection and stimulate brain repairing processes. Conditioning the central nervous system can trigger endogenous mechanisms of neuroprotection. Conditioning refers to a procedure by which a potentially deleterious stimulus is applied near to but below the threshold of damage to the organism. While hypoxia is well recognized as a common underlying mechanism of many pathological conditions, experimental data indicate that exposure to specific doses of hypoxia (by breathing a hypoxic gas mixture) can be neuroprotective.
Preconditioning is defined as the exposure to the conditioning stimulus before injury onset, to induce tolerance or resistance to the subsequent injury. Postconditioning refers to the application of the conditioning stimulus after injury or damage, to stimulate tissue reparation or neuroplasticity. As stroke is an unpredictable event, translating hypoxic preconditioning to clinical practice seems difficult. However, developing postconditioning strategies seems of clinical and rehabilitative relevance. Thus, an increase in neuronal salvage and neurogenesis, along with an increase in brain-derived neurotrophic factor expression and a reduced neuroinflammation were shown in murine models of hypoxic conditioning following ischemic stroke.
By inducing endogenous neuroprotection, hypoxic conditioning may represent a harmless and efficient non-pharmacological innovative neuro-therapeutic modality aiming at inducing neuroplasticity and brain repair, as supported by many preclinical studies.
The main working hypothesis is that hypoxic postconditioning may represent a safe therapeutic strategy post-stroke.
The investigators further hypothesize that hypoxic conditioning could enhance neuroplasticity and function in combination with conventional rehabilitative care.
The primary study endpoint will be safety. Safety will be assessed through the clinical review of the adverse events over the duration of the study, every 48 hours by a trained evaluator, blinded for the therapeutic intervention.
All adverse events will be evaluated and quoted in accordance with National Institute of Health Common Criteria for Terminology for Adverse Events 5.0 (NIH CCTAE) recommendations, particularly with respect to Sub-sections "Cardiac disorders ", "Nervous system disorders" and "Vascular Disorders". Safety assessments will be performed every 48 hours, throughout the 8-week conditioning period, in addition to the conventional clinical follow-up performed in the rehabilitation unit.
The potential functional benefits of such a therapeutic approach on motor function, gait, balance, and cognition will also be further investigated. The neurophysiological substrates of hypoxic conditioning-triggered neuroplasticity at a subacute delay post-stroke will be investigated, based on biological (serum inflammatory markers, growth and neurogenesis biomarkers) and imagery markers (morphological MRI sequences, functional connectivity (resting state), and brain vascularization).
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 3
- Model description
- Phase I (safety and tolerability) clinical trial (impact on intermediate endpoints) evaluating a chronic (one month) hypoxic conditioning strategy for stroke, single-center, dose-escalation accelerated titration design (Liu S., Contemp. Clin. Trials. 2013) with continuous safety reassessment method. Dose escalation protocol. Dose escalation consisting of 4 successive steps, with increasing doses of hypoxia and continuous reassessment of safety criteria (primary endpoint, see below) Phase 2: Randomised, double-blind, controlled study comparing a group exposed to intermittent hypoxic post-conditioning versus a group exposed for the same duration and under the same conditions to a normoxic stimulus.
| Arm | Type | Receives |
|---|---|---|
| PHASE 1- Dose escalation protocol | Experimental | Drug: Hypoxia, intermittent4-step dose-escalation protocol with increasing doses of intermittent hypoxia and continuous reassessment of safety criteria (primary endpoint). Hypoxic conditioning will be performed in three one-hour sessions per week, performed non-consecutively, for 8 weeks. The hypoxic stimulus will be intermittent, and each session will consist of 7 cycles of 5 minutes of hypoxia alternating with 3 minutes of normoxia (FiO2 = 21%). The subjects will be installed in a semi-recumbent position, at rest in a quiet environment. For hypoxic exposure, the inspired fraction of oxygen (FiO2) will be set individually to achieve the targeted level of desaturation (Pulse Oxygen Saturation, SpO2) continuously monitored: 90% for stage 1 (n=1 patient), 85% for stage 2 (n=3 patients), 80% for stage 3 (n=3 patients), 75% for stage 4 (n=3 patients). |
| PHASE 2 - Intermittent hypoxia group | Active comparator | Drug: Hypoxia, intermittentGroup exposed to an intermittent hypoxic stimulus (n=20, target pulsed saturation in dioxygen 75%). The device used is a gas mixer already in use in the unit and used in current clinical practice and research in our team (Altitrainer®, Sport and Medical TEChnologies S.A. (SMTEC S.A.), Switzerland). The hypoxic stimulus will be obtained by having the subject inhale a gas mixture enriched in nitrogen by means of a mask, in variable proportion according to the desired degree of hypoxia. Hypoxic conditioning will be performed in three one-hour sessions per week, performed non-consecutively, for 8 weeks. The hypoxic stimulus will be intermittent, and each session will consist of 7 cycles of 5 minutes of hypoxia alternating with 3 minutes of normoxia (FiO2 = 21%). The subjects will be installed in a semi-recumbent position, at rest in a quiet environment. For hypoxic exposure, the FiO2 will be set individually to achieve the targeted level of desaturation. |
| PHASE 2 - Sham (Normoxia) group | Sham comparator | Other: NormoxiaNormoxia group (n=10, FiO2 = 21%). The same setting will be used as in the Intermittent hypoxia group, but subjects will breathe ambient air throughout the conditioning procedure. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with minor cerebral infarction with NIHSS < or equal to 5 will be included in the protocol;
- Cerebral infarction occurring one month (±1 week) before the planned start of hypoxic exposure;
- Age ≥18 years;
- A first, unilateral, ischemic, supra-tentorial hemispheric stroke, confirmed by magnetic resonance imaging;
- Modified Rankin Scale score between 1 and 3, defining mild to moderate residual functional disability.
Key exclusion criteria (17 listed)
- Patients who are minors or over 85 years of age, pregnant or breastfeeding women, or women of childbearing potential in the absence of highly effective contraception;
- Stroke of the brainstem or cerebellum ;
- Severe aphasia, limiting the ability to understand the protocol;
- History of central or peripheral neurological pathology;
- Modified Rankin Scale score >0 before stroke;
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 conditioning, HypoxiaThe device used to generate the intermittent hypoxia stimulus is a gas mixer used in current clinical practice and research (Altitrainer®, SMTEC S.A. Switzerland). The hypoxic stimulus will be obtained by having the subject inhale a gas mixture enriched in nitrogen by means of a mask, in variable proportion according to the desired degree of hypoxia. Hypoxic conditioning will be performed in three one-hour sessions per week, performed non-consecutively, for 8 weeks. The hypoxic stimulus will be intermittent, and each session will consist of 7 cycles of 5 minutes of hypoxia alternating with 3 minutes of normoxia (FiO2 = 21%). The subjects will be installed in a semi-recumbent position, at rest in a quiet environment. For hypoxic exposure, the inspired fraction of oxygen (FiO2) will be set individually to achieve the targeted level of desaturation (Pulse Oxygen Saturation, SpO2) continuously monitored. | Drug | PHASE 1- Dose escalation protocol, PHASE 2 - Intermittent hypoxia group |
| NormoxiaThe normoxic stimulus will be obtained by having the subjects inhale via a face mask a normoxic gas mixture with a fixed FiO2 of 21%, delivered by the gas mixing device (Altitrainer®, SMTEC S.A. Switzerland). | Other | PHASE 2 - Sham (Normoxia) group |
Primary outcome
Secondary adverse events
Time frame: Through study completion, an average of 8 weeks
The safety of such a therapeutic strategy will be assessed by systematic screening for adverse events at each conditioning session and at follow-up visits throughout the duration of exposure (8 weeks) by a trained experimenter, blinded to the therapeutic intervention. All adverse events will be assessed and scored as a composite endpoint according to the NIH CCTAE 5.0 (National Institute of Health Common Terminology Criteria for Adverse Events), including in particular those listed in the sub-sections on "Cardiological Pathologies", "Central Nervous System Pathologies" and "Vascular Pathologies".
14 secondary outcomes
Fugl-Meyer
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
New Functional ambulation category (nFAC) score
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Prospective collection of number of falls
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Modified Rankin Scale (mRS)
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Barthel index
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
16-item Stroke Impact Scale
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
10-metre walk test
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Timed-up and Go test
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Montreal Cognitive Assessment
Time frame: Phase 1: Inclusion, 2 months; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Morphological sequences
Time frame: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Diffusion and perfusion sequences
Time frame: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Cerebral blood flow
Time frame: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Magnetic resonance imagery - Resting state functional magnetic resonance imaging (fMRI)
Time frame: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Cerebral Blood Flow
Time frame: Phase 1: Inclusion; Phase 2: Inclusion, 2 months, 6 months
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2024.
- Background: PubMed 26157787Verges S, Chacaroun S, Godin-Ribuot D, Baillieul S. Hypoxic Conditioning as a New Therapeutic Modality. Front Pediatr. 2015 Jun 22;3:58. doi: 10.3389/fped.2015.00058. eCollection 2015.
- Background: PubMed 28585890Baillieul S, Chacaroun S, Doutreleau S, Detante O, Pepin JL, Verges S. Hypoxic conditioning and the central nervous system: A new therapeutic opportunity for brain and spinal cord injuries? Exp Biol Med (Maywood). 2017 Jun;242(11):1198-1206. doi: 10.1177/1535370217712691.
- Background: PubMed 33638916Burtscher J, Syed MMK, Lashuel HA, Millet GP. Hypoxia Conditioning as a Promising Therapeutic Target in Parkinson's Disease? Mov Disord. 2021 Apr;36(4):857-861. doi: 10.1002/mds.28544. Epub 2021 Feb 27.
- Individual participant dataSharing planned: Yes. Data collected for the study, including deidentified individual participant data will be made available to others following the publication of this article, for academic purposes (e.g., meta-analyses) on request to the principal investigator, after the publication of the results of the present study.
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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.
Sébastien BAI, MD PHD principal investigator
CHU Grenoble Alpes
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Hypoxia, intermittent and Normoxia in people with Stroke, Ischemic and Stroke Sequelae, run by University Hospital, Grenoble at 1 site in France.
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 7 inclusion and 17 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: withdrawn, as of the sponsor's last update on 4 Jun 2024. 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 France. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
The study was withdrawn before enrolling participants, so there are no results.
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?
Secondary adverse events (time frame: Through study completion, an average of 8 weeks). 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 NCT05210088, 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 4 Jun 2024.