Clinical trial NCT04793334: Underlying Mechanisms of Obesity-induced Obstructive Sleep Apnea
Official title: Underlying Mechanisms of Obesity-induced Obstructive Sleep Apnea
Study type: OBSERVATIONAL
Overall status: ENROLLING_BY_INVITATION
Conditions: Obstructive Sleep Apnea
Obesity
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
First posted: 2021-03-11
Enrollment: 110
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Noting the inclusion and exclusion criteria above, we aim to recruit 110 patients, anticipating 20% drop out and a final n of 90. Further, we aim for to recruit 60 participants with OSA and 30 participants without OSA.

Brief summary: Obesity is a common risk factor for the development of obstructive sleep apnea. However, not all subjects with obesity develop obstructive sleep apnea. This study will attempt to determine the mechanistic drivers between obesity and obstructive sleep apnea.

Detailed description: Obstructive sleep apnea (OSA) is a highly prevalent disease with major neurocognitive and cardiovascular sequelae. Obesity is a major risk factor for OSA, but the underlying mechanisms remain unclear. Given the rising prevalence of obesity and the lack of adequate therapies for some afflicted patients, further mechanistic work is clearly required. Bariatric surgery is being done increasingly with compelling outcome data emerging; however, clinical response to weight loss is highly variable. In some patients, OSA is not present at baseline, despite morbid obesity, in other patients, OSA resolves following bariatric surgery, while other patients have persistence of OSA despite weight loss, and still other patients can experience re-emergence of OSA in long term follow-up studies after bariatric surgery. OSA can occur due to several major pathophysiological factors including pharyngeal anatomy, pharyngeal dilator muscle dysfunction, unstable ventilatory control, end- expiratory lung volume and arousal threshold. As a result considerable complexity exists in the obesity/OSA relationship, suggesting the need for further research. First, the investigators will perform a baseline evaluation of pathophysiological traits among obese people prior to weight loss surgery. Because some people will have OSA and some will not, the investigators will define the potential mechanisms underlying OSA and potential protective mechanisms among obese people without OSA (pharyngeal critical closing pressure Pcrit primary outcome). Second, the investigators will re-evaluate these same individuals from the standpoint of sleep study and pathophysiological traits six months following bariatric surgery after a variable degree of weight loss. The investigators anticipate that some OSA patients will have resolution of OSA whereas others will have persistence of disease. For non-OSA patients undergoing weight loss, the investigators will have a positive control group which will allow the investigators to account for non-specific effects of weight loss. This aim will allow the investigators to test the hypothesis that pharyngeal mechanics is the predominant mechanism whereby weight loss leads to improvement in OSA. Third, the investigators will perform magnetic resonance imaging during wakefulness at functional residual capacity, total lung capacity and residual volume on participants at baseline and 6months following bariatric surgery. This aim will allow the investigators to perform structure/function assessments in our participants, to define the impact of weight loss on pharyngeal anatomy, and to quantify the lung volume dependence of the upper airway before and after weight loss. The acquired data will also be used for computational modeling including dynamic assessment of pharyngeal function during tidal breathing. As a result of the proposed research, the investigators are confident that the investigators will gain major insights into the as yet unanswered question "why does obesity (sometimes) cause sleep apnea". This research will have major therapeutic implications as it will allow the investigators to individualize therapy for afflicted patients.

Eligibility criteria: Inclusion Criteria:

* - Men and women
* Ages \>= 18-65 years old
* BMI 35 kg/m2--and above
* Scheduled for sleeve gastrectomy (bariatric surgery)

Exclusion Criteria:

* Any cardiovascular, pulmonary or renal disease other than well-controlled hypertension or asthma.
* Pregnancy
* Currently smoking
* Any respiratory disorder other than OSA or well controlled asthma
* contraindication to MRI

Primary outcomes:
measure: muscle traits contributing to OSA in obesity - change is being assessed over time
timeFrame: Time point 1: Within 1 month of bariatric surgery, Time point 2: 6 months following bariatric surgery
measure: changes in pcrit after bariatric surgery
timeFrame: Time point 1: Within 1 month of bariatric surgery, Time point 2: 6 months following bariatric surgery
measure: MRI upper airway changes following bariatric surgery - change is being assessed over time
timeFrame: Time point 1: Within 1 month of bariatric surgery, Time point 2: 6 months following bariatric surgery
Secondary outcomes:
measure: exploratory outcomes
timeFrame: Time point 1: Within 1 month of bariatric surgery, Time point 2: 6 months following bariatric surgery
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD - Altman Clinical Research Institute (ACTRI)
state: California
Study officials:
References: