Effect of Weight Loss From ESG Plus Lifestyle Changes vs. Lifestyle Changes Alone in Sleep Apnea Patients

Obesity increases the risk of Obstructive Sleep Apnea (OSA), a condition where breathing stops during sleep. This study aims to find out whether Endoscopic Sleeve Gastroplasty (ESG) with lifestyle changes (like diet and exercise) improves OSA symptoms better than lifestyle changes alone. ESG is a non-surgical procedure that reduces stomach size to help with weight loss. Early studies show ESG can lead to weight loss and may reduce OSA symptoms, but more research is needed. This study will compare both treatment approaches to see which is more effective in improving sleep and overall health in people with obesity and OSA.

• Primary Endpoints:

Change in OSA severity (measured by apnea-hypopnea index, AHI) from baseline at 12 months after study procedure by group.

• Secondary Endpoints:

Study procedure and / or device related SAEs for the ESG group only Responders to weight loss (≥ 10% Total Body Weight Loss, TBWL) with reduction in OSA severity (AHI reduction ≥ 50%) at 12 months after study procedure by group Weight loss (TBWL%) at each study visit by group Improvement in sleep quality (assessed using validated sleep questionnaires) from baseline at 12 months after study procedure by group Epworth Sleepiness Scale (ESS) Pittsburgh Sleep Quality Index (PSQI) Change in OSA severity from baseline at 24 months after study procedure for the ESG group Responders to weight loss (≥ 10% Total Body Weight Loss, TBWL) with reduction in OSA severity (AHI reduction ≥ 50%) at 24 months after study procedure for the ESG group

• Additional Endpoints:

Adverse event frequency related to the study procedure Responders to weight loss at each study visit by randomization group Change in OSA severity at each study visit by group Improvement in sleep quality from baseline at each study visit by group Changes in metabolic parameters: HbA1c, fasting glucose, lipid profile, and liver profile.

Changes in blood pressure and inflammatory markers (e.g., hs-CRP). Improvement in quality of life (assessed using validated questionnaires) from baseline at each study visit by group SF-36 IWQOL LITE-CT

Inclusion criteria

• Age > 18years.
• Obesity defined by ethnic specific BMI cut-offs through < 40 kg/m².
• Diagnosed with moderate to severe OSA (Apnea-Hypopnea Index [AHI] ≥15).
• Stable weight (< 5 kg change) within 3 months prior to screening
• Failure or inadequate weight loss with conservative methods:

• lifestyle modification. and/or
• anti-obesity medications
• No planned additional weight loss treatments (i.e. OTC supplements, pharmacotherapy or bariatric surgery) during the first 12-months following study treatment
• Willingness to comply with the study protocol, including in office follow-up visits and lifestyle modifications.
• Able to sign, understand, and sign a written Informed Consent Form to participate in the study.

Exclusion criteria

• Any previous or planned surgery for sleep apnea or major ear, nose, or throat surgery
• Significant craniofacial abnormalities that may affect breathing
• Diagnosis of central or mixed sleep apnea, or diagnosis of Cheyne-Stokes Respiration Obesity related
• History of disorder, other than OSA, associated with insomnia or excessive daytime sleepiness
• Obesity induced by other endocrinologic disorders, or monogenetic or syndromic forms of obesity
• Active device treatment of OSA other than continuous positive airway pressure therapy
• Requires the use of supplemental oxygen
• Previous bariatric surgery or any other gastrointestinal surgery where primary ESG will not be feasible.
• Active inflammatory bowel disease.
• Current or planned pregnancy or breastfeeding while participating in the study.
• Severe cardiopulmonary conditions contraindicating endoscopy.
• Uncontrolled psychiatric disorders.
• Eating disorder that will impact the ability of the subject to follow the lifestyle modification program
• History of substance abuse.
• Use of any over-the-counter or prescription medications that could affect the evaluation of excessive sleepiness
• Type 2 diabetics that has had a change within 3 months of the screening visit or planned change in medication for blood sugar management that has thee potential to impact weight loss (i.e. GLP-1 medications)