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

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).

Study Overview

• Status: Terminated
• Conditions: Sleep Apnea, Obstructive
• Intervention / Treatment: Procedure: Weight-loss (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:

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).

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	Subjects will be assessed between 9-12 months post surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)	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)	Subjects will be assessed between 9-12 months post surgery

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Atul Malhotra, MD, Brigham & Womens Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2012
• Primary Completion (Actual): January 1, 2017
• Study Completion (Actual): January 1, 2017

Study Registration Dates

• First Submitted: October 16, 2012
• First Submitted That Met QC Criteria: October 19, 2012
• First Posted (Estimate): October 23, 2012

Study Record Updates

• Last Update Posted (Actual): March 3, 2017
• Last Update Submitted That Met QC Criteria: February 28, 2017
• Last Verified: February 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea
• Other Study ID Numbers: BWH-2011P002188; 5K24HL093218 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO