Assessment of Sleep Apnea and Its Causes Before and After Weight Loss Surgery

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2012 by Brigham and Women's Hospital
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Atul Malhotra, MD, Brigham and Women's Hospital
ClinicalTrials.gov Identifier:
NCT01712269
First received: October 16, 2012
Last updated: October 19, 2012
Last verified: October 2012
  Purpose

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).


Condition Intervention
Sleep Apnea, Obstructive
Procedure: Weight-loss (bariatric) surgery

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Basic Science
Official Title: Understanding the Role Obesity Plays in the Pathogenesis of Obstructive Sleep Apnea

Resource links provided by NLM:


Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:
  • Model prediction of absence/presence of OSA [ Time Frame: Subjects will be assessed at baseline (pre-surgery) ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Apnea-Hypopnea Index [ Time Frame: Subjects will be assessed at baseline (pre-surgery) ] [ Designated as safety issue: No ]
    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)

  • Apnea-Hypopnea Index [ Time Frame: Subjects will be assessed between 9-12 months post surgery ] [ Designated as safety issue: No ]
    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)


Estimated Enrollment: 60
Study Start Date: October 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Weight-loss (bariatric) surgery
All subjects enrolled will undergo bariatric surgery to assist weight-loss
Procedure: Weight-loss (bariatric) surgery
Subjects will undergo bariatric surgery which will assist weight loss

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:

  1. The severity of OSA (apnea-hypopnea-index or AHI)
  2. The physiological traits responsible for OSA:

i. 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).

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Ages 18 - 65 years
  • BMI > 35kg/m2
  • Scheduled for weight-loss surgery

Exclusion Criteria:

  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01712269

Contacts
Contact: Bradley A Edwards, PhD 6177328456 baedwards@partners.org
Contact: Alison M Foster, RPSGT 6177328977 afoster2@partners.org

Locations
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02115
Sub-Investigator: Bradley A Edwards, PhD         
Sponsors and Collaborators
Brigham and Women's Hospital
Investigators
Principal Investigator: Atul Malhotra, MD Brigham & Womens Hospital
  More Information

No publications provided

Responsible Party: Atul Malhotra, MD, Associate Professor, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01712269     History of Changes
Other Study ID Numbers: BWH-2011P002188, 5K24HL093218
Study First Received: October 16, 2012
Last Updated: October 19, 2012
Health Authority: United States: Institutional Review Board
United States: Federal Government

Additional relevant MeSH terms:
Apnea
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Disorders
Nervous System Diseases

ClinicalTrials.gov processed this record on July 28, 2014