NormoxiaPERHYP1NCT02201875
Intrinsic Periodic Pattern of Breathing
An observational study of Normoxia and Hypoxia, run by Association pour la Recherche en Physiologie de l'Environnement at 1 site in France.
Trial summary
We made a fortuitous observation of periodic breathing in a healthy subject coming to our outpatient mountain medicine consultation at Avicenne hospital in Bobigny (France). During this consultation, subjects perform a hypoxia exercise test, which allows a good prediction of their risk factors for severe high altitude… Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- How many people
- 120 participants
- Where
- 1 siteFrance
- Study dates
- Sep 2014to Dec 2015
- Phase
- Observational
- 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 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Healthy subjects Patients with obstructive sleep apneas Patients with cardiac failure
Who may be able to join
- depending on the group: see definition of groups
Who cannot join
- BMI > 30
- history of severe cardiac arrhythmia
- pulmonary hypertension
- history of coronary disease
Trial locations and contacts
1 site in 1 country.
France1 site
Physiology Department
Bobigny, 93009
Jean-Paul Richalet, MD, PhD, 33148387758, richalet@univ-paris13.fr
Jean-Paul Richalet, MD, PhD
About this study
Official title: Study of Periodic Breathing in Healthy Humans
We made a fortuitous observation of periodic breathing in a healthy subject coming to our outpatient mountain medicine consultation at Avicenne hospital in Bobigny (France). During this consultation, subjects perform a hypoxia exercise test, which allows a good prediction of their risk factors for severe high altitude illnesses. Surprisingly, breath-by-breath recording of the ventilation signal showed a periodic breathing pattern, which increased when the subject started to exercise in hypoxic conditions and was maintained during normoxic exercise.
Therefore, our objective was to confirm this observation in a retrospective study led in 82 subjects who passed this test. We tested the hypothesis that subjects with a brisk ventilatory response to hypoxia might show a more pronounced periodic pattern of ventilation, due to a higher gain of the chemoreceptor feedback loop. Then, our objective is to investigate the mechanisms involved in the periodic pattern in healthy subjects, as a function of exercise intensity, altitude intensity, role of peripheral and central chemoreceptors to O2 and CO2. Finally, we want to investigate the possible role of this ventilatory instability in patients with obstructive or central apneas.
Read the detailed description
In a preliminary study, among the population coming to the outpatient consultation of mountain medicine at Avicenne hospital in 2012, 82 subjects (38 females and 44 males) were randomly selected and separated in two groups of 41 high and 41 low responders to hypoxia according to the median value of the hypoxic ventilatory response to hypoxia at exercise (HVRe > or < 0.84 L/min/kg) derived from the hypoxic exercise test (inspired fraction of O2: 0.115, exercise intensity of 30% of maximal aerobic power), as previously described.
The hypoxic exercise test consists in 4 successive phases of 3 to 4 minutes each with the following sequence: rest in normoxia (RN), rest in hypoxia (RH), exercise in hypoxia (EH) and exercise in normoxia (EN). Minute ventilation ( E, L.min-1) is measured through a metabograph (Vmax Encore, SensorMedics, Yorba Linda, CA). Pulse O2 saturation (SpO2, %) is measured by transcutaneous oximetry (Nellcor N-595, Nellcor, Pleasanton, CA) on a pre-warmed ear lobe. End tidal PCO2 (PETCO2) is measured by infrared thermopile (Vmax Encore, SensorMedics, Yorba Linda, CA). During the whole test, VE, SpO2 and PETCO2 were recorded breath-by-breath. Continuous blood pressure is measured by a Finapres system. Data are transferred to a computer for further spectrum analysis. A Fast Fourier Transform (FFT) is then applied to the ventilation signal in sequences of 128 points in each phase of the test. This method will allow us to detect the presence of peaks in the frequency domain of the ventilation signal. Two main parameters are derived from the FFT: the frequency in hertz (or period in seconds) of the larger peak and its power estimated as the area under the peak at ± 0.02 Hz around the peak (in L2.s-2).
The main study will be designed in order to unravel the mechanisms and role of these oscillations in ventilation. An overall population of 90 healthy subjects and 30 patients will be included in the study.
Step 1. Effect of exercise intensity.
Step 2. Effect of altitude level.
Step 3. Effect of the stimulation of central chemoreceptors by acetazolamide.
Step 4. Effect of inhibiting the peripheral chemoreceptors by hyperoxia.
Step 5. Effect of inhibiting the peripheral chemoreceptors by hyperoxia and stimulating the central chemoreceptors by hypercapnia.
Step 6. Evaluating the presence of these oscillations in patients with sleep apneas.
Step 7. Evaluating the presence of these oscillations in patients with cardiac failure.
- Conditions
- Normoxia, Hypoxia, Hyperoxia, Hypercapnia
- Keywords
- hypoxia, exercise, periodic breathing, hypercapnia, apneas, cardiac failure
- Medical subject headings
- Hypoxia, Hyperoxia, Hypercapnia, Motor Activity, Apnea, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Healthy subjects | male, aged 18-65 moderately trained healthy, no treatment | |
| obstructive sleep apneas | patients with apnea/hypopnea index > 15 BMI < 30 Age < 50 yrs | |
| cardiac failure | NYHA class I to III ejection fraction < 40% age < 65 yrs BMI < 30 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Periodic pattern of ventilation
Presence of oscillation in the ventilation signal
Measured: The measure is made at the end of the 6-min exercise period, only once in each condition (normoxia, hypoxia, hyperoxia, hypercapnia),
Secondary outcomes (2)
Oscillations in heart rate
Presence of oscillations in the beat-by-beat ECG signal with a specific peak in the frequency spectrum
Measured: The measure is made at the end of the 6-min exercise period, only once in each condition (normoxia, hypoxia, hyperoxia, hypercapnia)
Oscillations in arterial blood pressure
Presence of oscillations in the systolic/diastolic value of instant arterial blood pressure, measured non-invasively.
Measured: The measure is made at the end of the 6-min exercise period, only once in each condition (normoxia, hypoxia, hyperoxia, hypercapnia)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Jul 2014 (estimated)
- Study startSep 2014
- Primary completionJun 2015 (estimated)
- Study completionDec 2015 (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 NormoxiaStudies 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
- Observational
- Observational model
- Cohort
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Association pour la Recherche en Physiologie de l'Environnement
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Pr. Jean Paul RICHALET, Association pour la Recherche en Physiologie de l'Environnement
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02201875
- Sponsor's protocol ID
- PERHYP1
- Acronym
- PERHYP1
- Status last verified
- Jul 2014
- First submitted
- 22 Jan 2014
- Last updated
- 28 Jul 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Richalet JP, Larmignat P, Poitrine E, Letournel M, Canoui-Poitrine F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. Am J Respir Crit Care Med. 2012 Jan 15;185(2):192-8. doi: 10.1164/rccm.201108-1396OC. Epub 2011 Oct 27.
PubMed 22071330Hermand E, Pichon A, Lhuissier FJ, Richalet JP. Low-frequency ventilatory oscillations in hypoxia are a major contributor to the low-frequency component of heart rate variability. Eur J Appl Physiol. 2019 Aug;119(8):1769-1777. doi: 10.1007/s00421-019-04166-x. Epub 2019 Jun 1.
PubMed 31154522Hermand E, Lhuissier FJ, Richalet JP. Effect of dead space on breathing stability at exercise in hypoxia. Respir Physiol Neurobiol. 2017 Dec;246:26-32. doi: 10.1016/j.resp.2017.07.008. Epub 2017 Jul 29.
PubMed 28760461
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Study of Periodic Breathing in Healthy Humans
- ClinicalTrials.gov ID
- NCT02201875
- Acronym / sponsor ID
- PERHYP1 / PERHYP1
- Conditions
- Normoxia, Hypoxia, Hyperoxia, Hypercapnia
- Keywords
- hypoxia, exercise, periodic breathing, hypercapnia, apneas, cardiac failure
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- Association pour la Recherche en Physiologie de l'EnvironnementUniversity, hospital or other
- Study start
- Sep 2014
- Primary completion
- Jun 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 28 Jul 2014 (estimated)
- 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.
We made a fortuitous observation of periodic breathing in a healthy subject coming to our outpatient mountain medicine consultation at Avicenne hospital in Bobigny (France). During this consultation, subjects perform a hypoxia exercise test, which allows a good prediction of their risk factors for severe high altitude illnesses. Surprisingly, breath-by-breath recording of the ventilation signal showed a periodic breathing pattern, which increased when the subject started to exercise in hypoxic conditions and was maintained during normoxic exercise.
Therefore, our objective was to confirm this observation in a retrospective study led in 82 subjects who passed this test. We tested the hypothesis that subjects with a brisk ventilatory response to hypoxia might show a more pronounced periodic pattern of ventilation, due to a higher gain of the chemoreceptor feedback loop. Then, our objective is to investigate the mechanisms involved in the periodic pattern in healthy subjects, as a function of exercise intensity, altitude intensity, role of peripheral and central chemoreceptors to O2 and CO2. Finally, we want to investigate the possible role of this ventilatory instability in patients with obstructive or central apneas.
Detailed description
In a preliminary study, among the population coming to the outpatient consultation of mountain medicine at Avicenne hospital in 2012, 82 subjects (38 females and 44 males) were randomly selected and separated in two groups of 41 high and 41 low responders to hypoxia according to the median value of the hypoxic ventilatory response to hypoxia at exercise (HVRe > or < 0.84 L/min/kg) derived from the hypoxic exercise test (inspired fraction of O2: 0.115, exercise intensity of 30% of maximal aerobic power), as previously described.
The hypoxic exercise test consists in 4 successive phases of 3 to 4 minutes each with the following sequence: rest in normoxia (RN), rest in hypoxia (RH), exercise in hypoxia (EH) and exercise in normoxia (EN). Minute ventilation ( E, L.min-1) is measured through a metabograph (Vmax Encore, SensorMedics, Yorba Linda, CA). Pulse O2 saturation (SpO2, %) is measured by transcutaneous oximetry (Nellcor N-595, Nellcor, Pleasanton, CA) on a pre-warmed ear lobe. End tidal PCO2 (PETCO2) is measured by infrared thermopile (Vmax Encore, SensorMedics, Yorba Linda, CA). During the whole test, VE, SpO2 and PETCO2 were recorded breath-by-breath. Continuous blood pressure is measured by a Finapres system. Data are transferred to a computer for further spectrum analysis. A Fast Fourier Transform (FFT) is then applied to the ventilation signal in sequences of 128 points in each phase of the test. This method will allow us to detect the presence of peaks in the frequency domain of the ventilation signal. Two main parameters are derived from the FFT: the frequency in hertz (or period in seconds) of the larger peak and its power estimated as the area under the peak at ± 0.02 Hz around the peak (in L2.s-2).
The main study will be designed in order to unravel the mechanisms and role of these oscillations in ventilation. An overall population of 90 healthy subjects and 30 patients will be included in the study.
Step 1. Effect of exercise intensity.
Step 2. Effect of altitude level.
Step 3. Effect of the stimulation of central chemoreceptors by acetazolamide.
Step 4. Effect of inhibiting the peripheral chemoreceptors by hyperoxia.
Step 5. Effect of inhibiting the peripheral chemoreceptors by hyperoxia and stimulating the central chemoreceptors by hypercapnia.
Step 6. Evaluating the presence of these oscillations in patients with sleep apneas.
Step 7. Evaluating the presence of these oscillations in patients with cardiac failure.
Study design
- Observational model
- Cohort
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Healthy subjects | – | –male, aged 18-65 moderately trained healthy, no treatment |
| obstructive sleep apneas | – | –patients with apnea/hypopnea index > 15 BMI < 30 Age < 50 yrs |
| cardiac failure | – | –NYHA class I to III ejection fraction < 40% age < 65 yrs BMI < 30 |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Healthy subjects Patients with obstructive sleep apneas Patients with cardiac failure
Key inclusion criteria (1 listed)
- depending on the group: see definition of groups
Key exclusion criteria (4 listed)
- BMI > 30
- history of severe cardiac arrhythmia
- pulmonary hypertension
- history of coronary disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Periodic pattern of ventilation
Time frame: The measure is made at the end of the 6-min exercise period, only once in each condition (normoxia, hypoxia, hyperoxia, hypercapnia),
Presence of oscillation in the ventilation signal
2 secondary outcomes
Oscillations in heart rate
Time frame: The measure is made at the end of the 6-min exercise period, only once in each condition (normoxia, hypoxia, hyperoxia, hypercapnia)
Oscillations in arterial blood pressure
Time frame: The measure is made at the end of the 6-min exercise period, only once in each condition (normoxia, hypoxia, hyperoxia, hypercapnia)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2014.
- Background: PubMed 22071330Richalet JP, Larmignat P, Poitrine E, Letournel M, Canoui-Poitrine F. Physiological risk factors for severe high-altitude illness: a prospective cohort study. Am J Respir Crit Care Med. 2012 Jan 15;185(2):192-8. doi: 10.1164/rccm.201108-1396OC. Epub 2011 Oct 27.
- Derived from this study: PubMed 31154522Hermand E, Pichon A, Lhuissier FJ, Richalet JP. Low-frequency ventilatory oscillations in hypoxia are a major contributor to the low-frequency component of heart rate variability. Eur J Appl Physiol. 2019 Aug;119(8):1769-1777. doi: 10.1007/s00421-019-04166-x. Epub 2019 Jun 1.
- Derived from this study: PubMed 28760461Hermand E, Lhuissier FJ, Richalet JP. Effect of dead space on breathing stability at exercise in hypoxia. Respir Physiol Neurobiol. 2017 Dec;246:26-32. doi: 10.1016/j.resp.2017.07.008. Epub 2017 Jul 29.
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Enrolling by invitation
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High-intensity Strenght Training in Normoxia (H-N), Low-intensity Strenght Training in Normoxia (L-N)
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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Normoxia and Hypoxia, run by Association pour la Recherche en Physiologie de l'Environnement 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 1 inclusion and 4 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 28 Jul 2014. 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. 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?
Contact Jean-Paul Richalet, MD, PhD (33148387758, richalet@univ-paris13.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Periodic pattern of ventilation (time frame: The measure is made at the end of the 6-min exercise period, only once in each condition (normoxia, hypoxia, hyperoxia, hypercapnia),). 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 NCT02201875, 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 28 Jul 2014; AzTrials last refreshed its copy on 30 Oct 2026.