Sleep Apnea, ObstructiveNCT01712269
Assessment of Sleep Apnea and Its Causes Before and After Weight Loss Surgery
A study testing Weight-loss (bariatric) surgery in people with Sleep Apnea, Obstructive, run by Brigham and Women's Hospital at 1 site in United States.
Trial summary
The central aim of this research project is to determine how the ever-growing problem of obesity in the western world contributes to the pathophysiology of obstructive sleep apnea (OSA). To complete this aim, the investigators will determine the impact of obesity on the mechanisms underlying OSA. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Sleep Apnea, Obstructive
- What is being tested?
- Weight-loss (bariatric) surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2012to Jan 2017
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ages 18 - 65 years
- BMI > 35kg/m2
- Scheduled for weight-loss surgery
Who cannot join
- Previous history of bariatric surgery
- Any serious medical condition (except controlled hypertension and diabetes)
- Any sleep disorder except OSA (RLS, insomnia, etc.)
- Use of medications known to affect sleep/arousal, breathing, or muscle physiology
- Allergy to lidocaine or Afrin
- History of current cigarette smoking or previous smoking history >10 pack years
Trial locations and contacts
1 site in 1 country.
United States1 site
Brigham and Women's Hospital
Boston, Massachusetts, 02115
About this study
Official title: Understanding the Role Obesity Plays in the Pathogenesis of Obstructive Sleep Apnea
The central aim of this research project is to determine how the ever-growing problem of obesity in the western world contributes to the pathophysiology of obstructive sleep apnea (OSA). To complete this aim, the investigators will determine the impact of obesity on the mechanisms underlying OSA. This will be achieved by making physiological measurements of 4 physiological traits known to cause OSA as well as the patients sleep apnea severity, before and after weight-loss surgery (i.e. bariatric surgery).
Read the detailed description
Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and cause intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such processes disturb normal sleep and impair neurocognitive function, often resulting in excessive daytime sleepiness and decreased quality of life. Furthermore, OSA is associated with cardiovascular morbidity and mortality, making OSA a major health concern. Obesity is categorically the major risk factor for OSA, with available data indicating a prevalence of 40% in obese men (BMI > 30kg/m2) and up to 90% in morbidly obese individuals (BMI > 40kg/m2). Given the prevalence of obesity has risen to epidemic proportions, with approximately 60% of adults considered overweight and 30% obese, it has become one of the world's leading health care concerns and research priorities. Importantly, as the prevalence of obesity continues to rise, so too does the number of individuals developing OSA. Surprisingly, despite the dominant role played by obesity in OSA pathogenesis, the precise mechanisms by which obesity leads to OSA are unclear
Current evidence suggests that OSA pathogenesis involves the interactions of at least four physiological traits comprising 1) the pharyngeal anatomy and its propensity towards collapse 2) the ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation), 3) the arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep) and 4) the stability of ventilatory feedback loop (i.e. loop gain). The potential mechanisms by which obesity may alter the four traits has to date not been carefully assessed. Specifically, obesity has been suggested to a) compromise the anatomy by decreasing the airway size and increasing its collapsibility, but it may also b) impair neuromuscular compensation by increasing the mechanical load placed on the upper airway muscles, c) increase the loop gain and destabilize breathing potentially via reductions in lung volume and increased chemosensitivity or d) increase the arousal threshold and thereby reduce the propensity to arouse from sleep which may offset some of the obesity-related deficits in the other traits. However, we do not know how obesity alters these four traits (in the same individual) and whether it involves predominantly one or several of the mechanistic pathways.
Therefore the aim of our study is to determine the impact of obesity on the mechanisms underlying OSA. This will be achieved by making physiological measurements before and after weight-loss surgery (i.e. bariatric surgery). Specifically we will assess:
- The severity of OSA (apnea-hypopnea-index or AHI)
- The physiological traits responsible for OSA:
- Pharyngeal anatomy and its propensity towards collapse ii. The ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation). iii. Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep). iv. Stability of ventilatory feedback loop (i.e. loop gain).
- Conditions
- Sleep Apnea, Obstructive
- Being tested
- Weight-loss (bariatric) surgery
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Weight-loss (bariatric) surgeryProcedure or surgery
Subjects will undergo bariatric surgery which will assist weight loss
| Study group | Role | What they receive |
|---|---|---|
| Weight-loss (bariatric) surgery | Experimental | All subjects enrolled will undergo bariatric surgery to assist weight-loss Receives: Procedure: Weight-loss (bariatric) surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Model prediction of absence/presence of OSA
Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.
Measured: Subjects will be assessed at baseline (pre-surgery)
Model prediction of absence/presence of OSA
Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.
Measured: Subjects will be assessed between 9-12 months post surgery
Secondary outcomes (2)
Apnea-Hypopnea Index
The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow)
Measured: Subjects will be assessed at baseline (pre-surgery)
Apnea-Hypopnea Index
The Apnea-Hypopnea Index (AHI) is an index of sleep apnea severity that encompasses the frequency of apneas (cessations in breathing) and hypopneas (reductions in airflow)
Measured: Subjects will be assessed between 9-12 months post surgery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Oct 2012 (estimated)
- Study startOct 2012
- Primary completionJan 2017
- Study completionJan 2017
Why it stopped: PI and main Co-I (Dr Edwards) relocated locations
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Sleep Apnea, ObstructiveStudies of the same condition, open and under way.
- More trials run by Brigham and Women's HospitalThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brigham and Women's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Responsible party
- Principal investigator, Atul Malhotra, MD, Brigham and Women's Hospital
- Investigators
- Atul Malhotra, MD, Principal investigator, Brigham & Womens Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01712269
- Sponsor's protocol ID
- BWH-2011P002188
- Other IDs
- 5K24HL093218
- Status last verified
- Feb 2017
- First submitted
- 16 Oct 2012
- Last updated
- 3 Mar 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 3 Mar 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Understanding the Role Obesity Plays in the Pathogenesis of Obstructive Sleep Apnea
- ClinicalTrials.gov ID
- NCT01712269
- Acronym / sponsor ID
- BWH-2011P002188
- Conditions
- Sleep Apnea, Obstructive
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: PI and main Co-I (Dr Edwards) relocated locations
- Enrolment
- 10 participants (actual)
- Lead sponsor
- Brigham and Women's HospitalUniversity, hospital or other
- Collaborators
- National Heart, Lung, and Blood Institute (NHLBI)
- Study start
- Oct 2012
- Primary completion
- Jan 2017 (actual)
- Study completion
- Jan 2017 (actual)
- First posted
- 23 Oct 2012 (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.
The central aim of this research project is to determine how the ever-growing problem of obesity in the western world contributes to the pathophysiology of obstructive sleep apnea (OSA). To complete this aim, the investigators will determine the impact of obesity on the mechanisms underlying OSA. This will be achieved by making physiological measurements of 4 physiological traits known to cause OSA as well as the patients sleep apnea severity, before and after weight-loss surgery (i.e. bariatric surgery).
Detailed description
Obstructive sleep apnea (OSA) is characterized by repetitive collapse or 'obstruction' of the pharyngeal airway during sleep. These obstructions result in repetitive hypopneas/apneas and cause intermittent hypoxia/hypercapnia, as well as surges in sympathetic activity. Such processes disturb normal sleep and impair neurocognitive function, often resulting in excessive daytime sleepiness and decreased quality of life. Furthermore, OSA is associated with cardiovascular morbidity and mortality, making OSA a major health concern. Obesity is categorically the major risk factor for OSA, with available data indicating a prevalence of 40% in obese men (BMI > 30kg/m2) and up to 90% in morbidly obese individuals (BMI > 40kg/m2). Given the prevalence of obesity has risen to epidemic proportions, with approximately 60% of adults considered overweight and 30% obese, it has become one of the world's leading health care concerns and research priorities. Importantly, as the prevalence of obesity continues to rise, so too does the number of individuals developing OSA. Surprisingly, despite the dominant role played by obesity in OSA pathogenesis, the precise mechanisms by which obesity leads to OSA are unclear
Current evidence suggests that OSA pathogenesis involves the interactions of at least four physiological traits comprising 1) the pharyngeal anatomy and its propensity towards collapse 2) the ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation), 3) the arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep) and 4) the stability of ventilatory feedback loop (i.e. loop gain). The potential mechanisms by which obesity may alter the four traits has to date not been carefully assessed. Specifically, obesity has been suggested to a) compromise the anatomy by decreasing the airway size and increasing its collapsibility, but it may also b) impair neuromuscular compensation by increasing the mechanical load placed on the upper airway muscles, c) increase the loop gain and destabilize breathing potentially via reductions in lung volume and increased chemosensitivity or d) increase the arousal threshold and thereby reduce the propensity to arouse from sleep which may offset some of the obesity-related deficits in the other traits. However, we do not know how obesity alters these four traits (in the same individual) and whether it involves predominantly one or several of the mechanistic pathways.
Therefore the aim of our study is to determine the impact of obesity on the mechanisms underlying OSA. This will be achieved by making physiological measurements before and after weight-loss surgery (i.e. bariatric surgery). Specifically we will assess:
- The severity of OSA (apnea-hypopnea-index or AHI)
- The physiological traits responsible for OSA:
- Pharyngeal anatomy and its propensity towards collapse ii. The ability of the upper airway dilator muscles to activate and reopen the airway during sleep (i.e. neuromuscular compensation). iii. Arousal threshold from sleep (i.e. the propensity for hypopneas/apneas to lead to arousal and fragmented sleep). iv. Stability of ventilatory feedback loop (i.e. loop gain).
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Weight-loss (bariatric) surgery | Experimental | Procedure: Weight-loss (bariatric) surgeryAll subjects enrolled will undergo bariatric surgery to assist weight-loss |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Ages 18 - 65 years
- BMI > 35kg/m2
- Scheduled for weight-loss surgery
Key exclusion criteria (6 listed)
- Previous history of bariatric surgery
- Any serious medical condition (except controlled hypertension and diabetes)
- Any sleep disorder except OSA (RLS, insomnia, etc.)
- Use of medications known to affect sleep/arousal, breathing, or muscle physiology
- Allergy to lidocaine or Afrin
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 |
|---|---|---|
| Weight-loss (bariatric) surgerySubjects will undergo bariatric surgery which will assist weight loss | Procedure or surgery | Weight-loss (bariatric) surgery |
Primary outcome
Model prediction of absence/presence of OSA
Time frame: Subjects will be assessed at baseline (pre-surgery)
Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.
Model prediction of absence/presence of OSA
Time frame: Subjects will be assessed between 9-12 months post surgery
Our published method estimates 4 important physiological traits causing OSA: 1) pharyngeal anatomy, 2) loop gain, 3) the ability of the upper airway to dilate/stiffen in response to increases in ventilatory drive, and 4) arousal threshold. These variables are measured using a single maneuver in which CPAP is dropped from an optimum to various suboptimum pressures during sleep. Each individual's set of traits is then entered into a physiological model of OSA that graphically illustrates the relative importance of each trait in that individual and predicts OSA presence/absence.
2 secondary outcomes
Apnea-Hypopnea Index
Time frame: Subjects will be assessed at baseline (pre-surgery)
Apnea-Hypopnea Index
Time frame: Subjects will be assessed between 9-12 months post surgery
Results and safety
The study was stopped early (reason given: PI and main Co-I (Dr Edwards) relocated locations). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Mar 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Atul Malhotra, MD principal investigator
Brigham & Womens Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Weight-loss (bariatric) surgery in people with Sleep Apnea, Obstructive, run by Brigham and Women's Hospital at 1 site in United States.
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 3 inclusion and 6 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 3 Mar 2017. 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 United States. 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?
The study was stopped early (reason given: PI and main Co-I (Dr Edwards) relocated locations). 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?
Model prediction of absence/presence of OSA (time frame: Subjects will be assessed at baseline (pre-surgery)). The study lists 2 primary outcomes in all. 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 3 Mar 2017.