CHEYNE Stokes RespirationPhase 1PERIODIBACNCT01095679
Baclofen and Hypoxia-induced Periodic Ventilation
A Phase 1 study testing Baclofen in people with CHEYNE Stokes Respiration, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Periodic ventilation that includes CHEYNE Stokes ventilation is a pathological pattern characterized by alternating periods of hyperpneas and apnea-hypopneas. It occurs generally during sleep, at high altitude and in hypoxic conditions in healthy subjects, and in some diseases like congestive heart failure. Read more about this study
- Who is it for?
- Ages 18 to 35 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- CHEYNE Stokes Respiration
- What is being tested?
- Baclofen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 53 participants
- Where
- 1 siteFrance
- Study dates
- Mar 2010to Sep 2011
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 35 years
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Adult
- Male
- Body mass index between 20 and 30 kg/m2
- Healthy (no known disease)
- No regular treatment except first grade antalgic drugs (e. g. ACETAMINOFEN)
- Written consent to participate in the study
- Health insurance
Who cannot join
- Intolerance to baclofen
- Tobacco, alcohol or drug consumption
- Past history of possible acute mountain sickness
- Regular treatment for any disease
- Claustrophobia
- Coronary disease
Show all 24Show fewer
- Hypertension
- Cardiac failure
- Cardiac rhythm abnormalities
- Pulmonary hypertension
- Any pulmonary artery abnormality
- Any cardiac disease
- Past history of cerebral ischemia
- Past history of psychiatric disorder
- Any respiratory disease (including asthma)
- Leg arteriopathy
- Sickle cell anemia
- Renal insufficiency
- Migraine
- Diabetes
- Obesity
- Thalassemia
- Scoliosis
- Past history of phlebitis
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Assessment of the Effect of the GABA-B Receptor Agonist, Baclofen, on Hypoxia-induced Periodic Ventilation, in Healthy Subjects
Periodic ventilation that includes CHEYNE Stokes ventilation is a pathological pattern characterized by alternating periods of hyperpneas and apnea-hypopneas. It occurs generally during sleep, at high altitude and in hypoxic conditions in healthy subjects, and in some diseases like congestive heart failure. One study conducted on an animal model suggested that baclofen, a drug already used against spasticity in humans, could also be effective against periodic ventilation. The goal of the study is therefore to assess this hypothesis on hypoxia-induced periodic ventilation in healthy subjects during sleep.
Read the detailed description
Rationale of the study:
Periodic ventilation, often called CHEYNE Stokes ventilation, results from a dysfunction of the mechanisms of the control of breathing. In this type of ventilation, alternating periods of hyperventilation and apneas and/or hypoventilation replace the normal regular pattern of breathing. Periodic ventilation occurs preferentially during sleep. It is responsible for decreases in arterial saturation in oxygen and for sleep fragmentation. There is currently no consensual treatment but non-invasive nocturnal mechanical ventilation is often used to bring the ventilatory pattern back to normal.
Periodic ventilation occurs in various conditions, the most frequent being cardiac failure. It also occurs in healthy subjects exposed to hypoxia or at high altitude.
The pathophysiology of periodic breathing remains poorly understood. Our hypothesis regarding the mechanisms of this abnormal ventilatory pattern is based on comparative physiology. Periodic ventilation is indeed the usual ventilatory pattern of many lower vertebrates. Moreover, even isolated in VITRO, the tadpole brainstem still produces a periodic ventilatory rhythm, characterized by clusters of ventilatory discharges. In this model, the agonist of the GABA-B receptor, the baclofen, transforms the periodic pattern into a regular one. Of note, the baclofen is already used in the treatment of some human diseases, especially against spasticity.
The hypothesis of the research project assumes that periodic ventilation in humans results from a neural reconfiguration of the networks that command breathing, leading them to produce an ancestral behavior. It also assumes that the baclofen woul reverse this phenomenon as it does in the model of the tadpole isolated brainstem.
The goal of the project is therefore to assess the effect of baclofen on hypoxia-induced periodic ventilation in healthy subjects during sleep. This is thus a pathophysiological study that aimed at demonstrating a concept before a possible clinical trial.
This study is pathophysiological study, conducted in healthy volunteers only.
Methods:
The subjects will sleep in hypoxic conditions, with a level of hypoxia similar to the one that is found at an altitude of 4000-4500 meters. A this altitude, the partial pressure of oxygen is approximately 90-100 mmHg. The hypoxic atmosphere will be created in a tent with an hypoxic generator (EVEREST Summit Hypoxic Generator, Hypoxic Systems, New York, NY, USA).
The electroencephalographic and electrocardiographic signals and the movements of the chest and of the abdomen will be recorded with a portable polysomnograph. The electromyogram of the chin and the ELECTRO Oculogram will also be recorded. These signals will permit to identify the sleep stages. The subjects will ware a face mask connected to a pneumotachometer for the recording of the ventilatory flow. Gas will also be sampled to measure the end tidal partial pressure of CO2.
Protocol:
Healthy volunteers will be enrolled after they will have given written informed consent. The subjects will be asked about their medical history and physical examination will be performed. Chest X-ray, electrocardiogram and pulmonary function tests will also be performed.
The subject will be asked not to sleep the night before each recording in hypoxic conditions (the hypoxic sessions). The recordings will be performed either during a nap in the afternoon or at night.
A first hypoxic session will be performed to identify the subjects who will develop periodic ventilation. Only those who will exhibit periodic ventilation during sleep will continue the study. They will be prescribed either baclofen or placebo (double blind, randomized). The posology will be progressively increased (over approximately 10 days) to reach 20 mg 3 times a day, during 3 to 5 days. A second hypoxic session will be performed under this treatment. Then the posology will be decreased over 3 days and a complete weaning will be performed during 5 to 10 days. The same protocol will be repeated, either with baclofen or placebo (depending of the previous run) and a third hypoxic session will be performed. The posology will then be decreased over 3 days and the study will be considered ended for the subject after 2 more days of complete weaning.
The maximum duration of the study for one subject will be 63 days.
- Conditions
- CHEYNE Stokes Respiration
- Being tested
- Baclofen, Placebo
- Keywords
- CHEYNE Stokes respiration, Periodic ventilation, baclofen, hypoxia, healthy subject
- Medical subject headings
- Cheyne-Stokes Respiration, Hypoxia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BaclofenDrug
Breaking tablets of 10 mg of baclofen. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day.
PlaceboDrug
Breaking tablets of 10 mg of placebo. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day.
| Study group | Role | What they receive |
|---|---|---|
| Baclofen | Experimental | Not described Receives: Drug: Baclofen |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Decrease in the coefficient of variation of the period of the ventilatory cycle
The primary outcome will be the decrease in the coefficient of variation of the period of the ventilatory cycle. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Measured: During the second and the third session in hypoxia
Secondary outcomes (6)
Decrease in the coefficient of variation of the tidal volume
Decrease in the coefficient of variation of the tidal volume. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Measured: During the second and the third session in hypoxia
Decrease in the coefficient of variation of the end tidal CO2 pressure
Decrease in the coefficient of variation of the end tidal CO2 pressure. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Measured: During the second and the third session in hypoxia
Decrease in the number of frequency compounds of the ventilatory flow
Decrease in the number of frequency compounds of the ventilatory flow. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Measured: During the second and the third session in hypoxia
Decrease in the apnea-hypopnea index
Decrease in the apnea-hypopnea index. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Measured: During the second and the third session in hypoxia
Decrease in the sleep fragmentation index
Decrease in the sleep fragmentation index. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Measured: During the second and the third session in hypoxia
Change in the non-linea dynamics of the ventilatory flow
Change in the non-linea dynamics of the ventilatory flow. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
Measured: During the second and the third session in hypoxia
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2010 (estimated)
- Study startMar 2010
- Primary completionSep 2011
- Study completionSep 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CHEYNE Stokes RespirationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 53 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Christian Straus, MD, PhD, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01095679
- Sponsor's protocol ID
- P090207
- Acronym
- PERIODIBAC
- Status last verified
- Dec 2009
- First submitted
- 29 Mar 2010
- Last updated
- 31 Oct 2012
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 31 Oct 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Assessment of the Effect of the GABA-B Receptor Agonist, Baclofen, on Hypoxia-induced Periodic Ventilation, in Healthy Subjects
- ClinicalTrials.gov ID
- NCT01095679
- Acronym / sponsor ID
- PERIODIBAC / P090207
- Conditions
- CHEYNE Stokes Respiration
- Keywords
- CHEYNE Stokes respiration, Periodic ventilation, baclofen, hypoxia, healthy subject
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 53 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Mar 2010
- Primary completion
- Sep 2011 (actual)
- Study completion
- Sep 2011 (actual)
- First posted
- 30 Mar 2010 (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.
Periodic ventilation that includes CHEYNE Stokes ventilation is a pathological pattern characterized by alternating periods of hyperpneas and apnea-hypopneas. It occurs generally during sleep, at high altitude and in hypoxic conditions in healthy subjects, and in some diseases like congestive heart failure. One study conducted on an animal model suggested that baclofen, a drug already used against spasticity in humans, could also be effective against periodic ventilation. The goal of the study is therefore to assess this hypothesis on hypoxia-induced periodic ventilation in healthy subjects during sleep.
Detailed description
Rationale of the study:
Periodic ventilation, often called CHEYNE Stokes ventilation, results from a dysfunction of the mechanisms of the control of breathing. In this type of ventilation, alternating periods of hyperventilation and apneas and/or hypoventilation replace the normal regular pattern of breathing. Periodic ventilation occurs preferentially during sleep. It is responsible for decreases in arterial saturation in oxygen and for sleep fragmentation. There is currently no consensual treatment but non-invasive nocturnal mechanical ventilation is often used to bring the ventilatory pattern back to normal.
Periodic ventilation occurs in various conditions, the most frequent being cardiac failure. It also occurs in healthy subjects exposed to hypoxia or at high altitude.
The pathophysiology of periodic breathing remains poorly understood. Our hypothesis regarding the mechanisms of this abnormal ventilatory pattern is based on comparative physiology. Periodic ventilation is indeed the usual ventilatory pattern of many lower vertebrates. Moreover, even isolated in VITRO, the tadpole brainstem still produces a periodic ventilatory rhythm, characterized by clusters of ventilatory discharges. In this model, the agonist of the GABA-B receptor, the baclofen, transforms the periodic pattern into a regular one. Of note, the baclofen is already used in the treatment of some human diseases, especially against spasticity.
The hypothesis of the research project assumes that periodic ventilation in humans results from a neural reconfiguration of the networks that command breathing, leading them to produce an ancestral behavior. It also assumes that the baclofen woul reverse this phenomenon as it does in the model of the tadpole isolated brainstem.
The goal of the project is therefore to assess the effect of baclofen on hypoxia-induced periodic ventilation in healthy subjects during sleep. This is thus a pathophysiological study that aimed at demonstrating a concept before a possible clinical trial.
This study is pathophysiological study, conducted in healthy volunteers only.
Methods:
The subjects will sleep in hypoxic conditions, with a level of hypoxia similar to the one that is found at an altitude of 4000-4500 meters. A this altitude, the partial pressure of oxygen is approximately 90-100 mmHg. The hypoxic atmosphere will be created in a tent with an hypoxic generator (EVEREST Summit Hypoxic Generator, Hypoxic Systems, New York, NY, USA).
The electroencephalographic and electrocardiographic signals and the movements of the chest and of the abdomen will be recorded with a portable polysomnograph. The electromyogram of the chin and the ELECTRO Oculogram will also be recorded. These signals will permit to identify the sleep stages. The subjects will ware a face mask connected to a pneumotachometer for the recording of the ventilatory flow. Gas will also be sampled to measure the end tidal partial pressure of CO2.
Protocol:
Healthy volunteers will be enrolled after they will have given written informed consent. The subjects will be asked about their medical history and physical examination will be performed. Chest X-ray, electrocardiogram and pulmonary function tests will also be performed.
The subject will be asked not to sleep the night before each recording in hypoxic conditions (the hypoxic sessions). The recordings will be performed either during a nap in the afternoon or at night.
A first hypoxic session will be performed to identify the subjects who will develop periodic ventilation. Only those who will exhibit periodic ventilation during sleep will continue the study. They will be prescribed either baclofen or placebo (double blind, randomized). The posology will be progressively increased (over approximately 10 days) to reach 20 mg 3 times a day, during 3 to 5 days. A second hypoxic session will be performed under this treatment. Then the posology will be decreased over 3 days and a complete weaning will be performed during 5 to 10 days. The same protocol will be repeated, either with baclofen or placebo (depending of the previous run) and a third hypoxic session will be performed. The posology will then be decreased over 3 days and the study will be considered ended for the subject after 2 more days of complete weaning.
The maximum duration of the study for one subject will be 63 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baclofen | Experimental | Drug: Baclofen |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 35 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (7 listed)
- Adult
- Male
- Body mass index between 20 and 30 kg/m2
- Healthy (no known disease)
- No regular treatment except first grade antalgic drugs (e. g. ACETAMINOFEN)
Key exclusion criteria (24 listed)
- Intolerance to baclofen
- Tobacco, alcohol or drug consumption
- Past history of possible acute mountain sickness
- Regular treatment for any disease
- Claustrophobia
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 |
|---|---|---|
| BaclofenBreaking tablets of 10 mg of baclofen. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day. | Drug | Baclofen |
| PlaceboBreaking tablets of 10 mg of placebo. Dosage and frequency : 5 mg 3 times a day for 3 days, then 10 mg 3 times a day for 3 days, then 15 mg 3 times a day for 3 days, then 20 mg 3 times a day for 3-5 days, then 15 mg 3 times a day for 1 day, then 10 mg 3 times a day for one day, then 5 mg 3 times a day for one day. | Drug | Placebo |
Primary outcome
Decrease in the coefficient of variation of the period of the ventilatory cycle
Time frame: During the second and the third session in hypoxia
The primary outcome will be the decrease in the coefficient of variation of the period of the ventilatory cycle. The measures will be taken during the second and the third session in hypoxia. This means, for each subject, after having taken either placebo or 60 mg per day of Baclofen for 3-5 days.
6 secondary outcomes
Decrease in the coefficient of variation of the tidal volume
Time frame: During the second and the third session in hypoxia
Decrease in the coefficient of variation of the end tidal CO2 pressure
Time frame: During the second and the third session in hypoxia
Decrease in the number of frequency compounds of the ventilatory flow
Time frame: During the second and the third session in hypoxia
Decrease in the apnea-hypopnea index
Time frame: During the second and the third session in hypoxia
Decrease in the sleep fragmentation index
Time frame: During the second and the third session in hypoxia
Change in the non-linea dynamics of the ventilatory flow
Time frame: During the second and the third session in hypoxia
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Oct 2012.
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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.
Christian Straus, MD, PhD principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Baclofen in people with CHEYNE Stokes Respiration, run by Assistance Publique - Hôpitaux de Paris 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 24 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: finished, as of the sponsor's last update on 31 Oct 2012. 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 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.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Decrease in the coefficient of variation of the period of the ventilatory cycle (time frame: During the second and the third session in hypoxia). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 31 Oct 2012.