Obstructive Sleep ApneaNCT01961648
Respiratory Drive on Obstructive Apnea
A study testing Rebreathing bag and Mask in people with Obstructive Sleep Apnea, run by University of Manitoba at 2 sites in Canada.
Trial summary
This study is being conducted to determine whether inhaling exhaled carbon dioxide is effective for the treatment of sleep apnea. A mild increase in this gas can stimulate the respiratory drive by 2-3 fold, which in turn can stimulate the upper airway dilator muscles and decrease the severity of obstructive sleep… Read more about this study
- Who is it for?
- Ages 21 to 70 years
- Conditions the study is for
- Obstructive Sleep Apnea
- What is being tested?
- Rebreathing bag and Mask
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 13 participants
- Where
- 2 sitesCanada
- Study dates
- Aug 2013to Jun 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Moderate to severe OSA Apnea Hypopnea Index > 20/hr.
- Minimum oxygen saturation by pulse oximetry (SpO2) during events >70% throughout sleep during the clinical sleep study
Who cannot join
- Neuromuscular disease.
- Obesity-hypoventilation syndrome.
- Chronic obstructive pulmonary disease.
- Pregnancy.
- Significant comorbidities:
- Dialysis-dependant renal failure
Show all 11Show fewer
- Severe asthma
- Congestive
- Heart failure
- Previous stroke
- Recent (within 3 months) myocardial infarction or Active coronary ischemia event.
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
Misericordia Medical Centre, Sleep Disorder Centre
Winnipeg, Manitoba, R3C 1A2
Sleep Disorder Centre at Misericordia Health Centre
Winnipeg, Manitoba, R3C 1A2
About this study
Official title: Effect of Increasing Respiratory Drive on Severity of Obstructive Apnea
This study is being conducted to determine whether inhaling exhaled carbon dioxide is effective for the treatment of sleep apnea. A mild increase in this gas can stimulate the respiratory drive by 2-3 fold, which in turn can stimulate the upper airway dilator muscles and decrease the severity of obstructive sleep apnea by at least 50% in selected patients.
Read the detailed description
During wakefulness pharyngeal dilator muscles (dilators) provide the necessary force to permit an adequate flow in all subjects regardless of how collapsible their passive pharynx is. This dilator activity is substantially lost at sleep onset. Subjects in whom the passive pharynx cannot permit adequate ventilation must recruit dilators through reflex mechanisms if they are to remain asleep. Dilators can be recruited reflexly via changes in blood gas tensions and in afferent activity of pharyngeal mechanoreceptors.
Patients with obstructive sleep apnea (OSA) develop repetitive obstructive events during which air flow decreases substantially (hypopneas) or ceases altogether (apneas). These last from 10 to >60 seconds following which there is a substantial increase in ventilation (hyperventilatory phase) that lasts for several breaths. The cycle then repeats. Arousal from sleep occurs at some point during the hyperventilatory phase in the vast majority of obstructive respiratory events. However it has been shown that in the majority of OSA patients, the reflex mechanisms are competent and can deal with the obstruction without arousal. The respiratory drive must increase a finite amount before the upper airway muscles begin responding to increasing respiratory drive, and often the patient wakes up first. Thus, when a subject with a narrowed or more compliant pharynx falls asleep and obstructs his/her airway, blood gas tensions must deteriorate a threshold amount before the pharyngeal dilators begin responding. Once this threshold is reached, the dilators respond briskly to further changes in blood gas tensions and open the airway. This threshold was termed the Effective Recruitment Threshold (TER).
The basis for this research project is that if respiratory drive can be maintained at or near the threshold, the dilators would respond promptly to any obstruction and there would be little further increase in respiratory drive during obstruction.We estimate that the required increase in drive can be attained by simply raising carbon dioxide pressure (PCO2) 2-3 mmHg, a highly tolerable increase. We intend to increase respiratory drive on a continuous basis, beginning before sleep by asking the participants to breath through a regular continuous positive airway pressure (CPAP) mask with added dead space.
To increase dead-space we will modify commercial rebreathing bags used for oxygen therapy so that the amount of rebreathing can be adjustable. This should raise arterial carbon dioxide pressure (PaCO2) a few millimetres of mercury (mmHg) in the steady state. Upon sleep, the respiratory drive would be at or above TER in nearly half the patients. Should the airway obstruct, the dilator muscles would be in a position to respond promptly, preventing an acute further rise in respiratory drive. This will reduce the frequency of obstructive respiratory events by >50% in at least half the patients, and improve sleep quality and nocturnal oxygen saturation.
- Conditions
- Obstructive Sleep Apnea
- Being tested
- Rebreathing bag, Sham rebreathing, Mask
- Keywords
- Apnea, Sleep Apnea Disorder, Respiratory chemical drive, CO2
- Medical subject headings
- Sleep Apnea, Obstructive, Apnea
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rebreathing bagDevice
Also called CO2 rebreathing, Dead space
Sham rebreathingDevice
Also called Room air
MaskDevice
| Study group | Role | What they receive |
|---|---|---|
| Dead space | Active comparator | Participant will sleep connected to a mask with added dead space half of the night Receives: Device: Rebreathing bag; Device: Mask |
| room air | Sham comparator | Participant will sleep connected to a mask open to rrom air, half of the night Receives: Device: Sham rebreathing; Device: Mask |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in total Apnea-hypopnea index (AHI)
We expect that at least half the patients will undergo >50% reduction in their AHI relative to the control part of the study. The baseline apnea-hypopnea index will be established during the sham intervention, and will be compared to the AHI at the end of the CO2 rebreathing intervention.
Measured: Eight to ten hours. Within the same study night, the AHI will be compared at baseline and at the end of the intervention period
Secondary outcomes (1)
Sleep quality as assessed by Total Sleep Time. Sleep Efficiency, and Arousal Index
The sleep architecture assessed by the sleep efficiency, number of arousals and awakenings, and the time awake after sleep onset (WASO) will be determined at baseline (sham) and compared after CO2 rebreathing intervention. If the apnea/hypopnea index is improved, the sleep quality is expected to improve accordingly, however, the intervention itself has the potential to disrupt sleep even when only minor changes in CO2 are expected.
Measured: Eight to ten hours. Within the same study night, the sleep quality conventional measurements will be compared at baseline and at the end of the intervention period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Oct 2013 (estimated)
- Study startAug 2013
- Primary completionJun 2014
- Study completionJun 2015
Why it stopped: Investigators were not able to continue recruiting and enrolling.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Obstructive Sleep ApneaStudies 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Manitoba
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01961648
- Sponsor's protocol ID
- B2012:132
- Status last verified
- Sep 2013
- First submitted
- 6 Sep 2013
- Last updated
- 29 Jun 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 29 Jun 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Increasing Respiratory Drive on Severity of Obstructive Apnea
- ClinicalTrials.gov ID
- NCT01961648
- Acronym / sponsor ID
- B2012:132
- Conditions
- Obstructive Sleep Apnea
- Keywords
- Apnea, Sleep Apnea Disorder, Respiratory chemical drive, CO2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Investigators were not able to continue recruiting and enrolling.
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of ManitobaUniversity, hospital or other
- Study start
- Aug 2013
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 11 Oct 2013 (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.
This study is being conducted to determine whether inhaling exhaled carbon dioxide is effective for the treatment of sleep apnea. A mild increase in this gas can stimulate the respiratory drive by 2-3 fold, which in turn can stimulate the upper airway dilator muscles and decrease the severity of obstructive sleep apnea by at least 50% in selected patients.
Detailed description
During wakefulness pharyngeal dilator muscles (dilators) provide the necessary force to permit an adequate flow in all subjects regardless of how collapsible their passive pharynx is. This dilator activity is substantially lost at sleep onset. Subjects in whom the passive pharynx cannot permit adequate ventilation must recruit dilators through reflex mechanisms if they are to remain asleep. Dilators can be recruited reflexly via changes in blood gas tensions and in afferent activity of pharyngeal mechanoreceptors.
Patients with obstructive sleep apnea (OSA) develop repetitive obstructive events during which air flow decreases substantially (hypopneas) or ceases altogether (apneas). These last from 10 to >60 seconds following which there is a substantial increase in ventilation (hyperventilatory phase) that lasts for several breaths. The cycle then repeats. Arousal from sleep occurs at some point during the hyperventilatory phase in the vast majority of obstructive respiratory events. However it has been shown that in the majority of OSA patients, the reflex mechanisms are competent and can deal with the obstruction without arousal. The respiratory drive must increase a finite amount before the upper airway muscles begin responding to increasing respiratory drive, and often the patient wakes up first. Thus, when a subject with a narrowed or more compliant pharynx falls asleep and obstructs his/her airway, blood gas tensions must deteriorate a threshold amount before the pharyngeal dilators begin responding. Once this threshold is reached, the dilators respond briskly to further changes in blood gas tensions and open the airway. This threshold was termed the Effective Recruitment Threshold (TER).
The basis for this research project is that if respiratory drive can be maintained at or near the threshold, the dilators would respond promptly to any obstruction and there would be little further increase in respiratory drive during obstruction.We estimate that the required increase in drive can be attained by simply raising carbon dioxide pressure (PCO2) 2-3 mmHg, a highly tolerable increase. We intend to increase respiratory drive on a continuous basis, beginning before sleep by asking the participants to breath through a regular continuous positive airway pressure (CPAP) mask with added dead space.
To increase dead-space we will modify commercial rebreathing bags used for oxygen therapy so that the amount of rebreathing can be adjustable. This should raise arterial carbon dioxide pressure (PaCO2) a few millimetres of mercury (mmHg) in the steady state. Upon sleep, the respiratory drive would be at or above TER in nearly half the patients. Should the airway obstruct, the dilator muscles would be in a position to respond promptly, preventing an acute further rise in respiratory drive. This will reduce the frequency of obstructive respiratory events by >50% in at least half the patients, and improve sleep quality and nocturnal oxygen saturation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Dead space | Active comparator | Device: Rebreathing bag, Device: MaskParticipant will sleep connected to a mask with added dead space half of the night |
| room air | Sham comparator | Device: Sham rebreathing, Device: MaskParticipant will sleep connected to a mask open to rrom air, half of the night |
Who may qualify
- Ages
- 21 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Moderate to severe OSA Apnea Hypopnea Index > 20/hr.
- Minimum oxygen saturation by pulse oximetry (SpO2) during events >70% throughout sleep during the clinical sleep study
Key exclusion criteria (11 listed)
- Neuromuscular disease.
- Obesity-hypoventilation syndrome.
- Chronic obstructive pulmonary disease.
- Pregnancy.
- Significant comorbidities:
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 |
|---|---|---|
| Rebreathing bagAlso: CO2 rebreathing, Dead space | Device | Dead space |
| Sham rebreathingAlso: Room air | Device | room air |
| Mask | Device | Dead space, room air |
Primary outcome
Change from baseline in total Apnea-hypopnea index (AHI)
Time frame: Eight to ten hours. Within the same study night, the AHI will be compared at baseline and at the end of the intervention period
We expect that at least half the patients will undergo >50% reduction in their AHI relative to the control part of the study. The baseline apnea-hypopnea index will be established during the sham intervention, and will be compared to the AHI at the end of the CO2 rebreathing intervention.
1 secondary outcome
Sleep quality as assessed by Total Sleep Time. Sleep Efficiency, and Arousal Index
Time frame: Eight to ten hours. Within the same study night, the sleep quality conventional measurements will be compared at baseline and at the end of the intervention period
Results and safety
The study was stopped early (reason given: Investigators were not able to continue recruiting and enrolling.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Jun 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rebreathing bag and Mask in people with Obstructive Sleep Apnea, run by University of Manitoba at 2 sites in Canada.
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 2 inclusion and 11 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: stopped early, as of the sponsor's last update on 29 Jun 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study was stopped early (reason given: Investigators were not able to continue recruiting and enrolling.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in total Apnea-hypopnea index (AHI) (time frame: Eight to ten hours. Within the same study night, the AHI will be compared at baseline and at the end of the intervention period). 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 29 Jun 2015.