Adipose Dysfunction, Imaging, Physiology, and Outcomes With Sodium Glucose Cotransporter 2 Inhibitor (SGLT2i) for Sleep Apnea: The ADIPOSA Study

Официальное название

Adipose Dysfunction, Imaging, Physiology, and Outcomes With SGLT2i's for Sleep Apnea: The ADIPOSA Study

Обзор

The goal of this clinical trial is to test if bexagliflozin lowers the sleep apnea severity in adults who are overweight or obese with moderate to severe obstructive sleep apnea (OSA) compared with a placebo (look-alike substance that contains no active drug). The main question it aims to answer is: * If SGLT2i will reduce anatomic and physiologic traits, clinical measures of OSA and sleep deficiency in participants * If improvement in clinical measures are because of improvement in the anatomic and physiologic traits. Participants will be placed on either drug or placebo and get routine normal care for 6 months. At the start and end of the study, participants will undergo different clinical measurements to see if the drug makes the sleep apnea better.

Подробное описание

The primary objective of this study is to determine whether bexagliflozin 20 mg once daily compared with placebo reduces the apnea hypopnea index (AHI) in adults with overweight or obesity with moderate to severe OSA.

The secondary objectives of this study are to determine whether bexagliflozin 20 mg once daily compared with placebo (a look-alike substance that contains no active drug):

* reduces visceral and neck fat and upper airway soft tissue structure volumes and increases airway caliber * reduces Critical closing pressure * reduces rostral to caudal fluid shifts (measured by neck circumference) * improves clinical measures of OSA severity and sleep deficiency

This is a 2-center clinical trial of overweight or obese adults (BMI 25-40 kg/m2) diagnosed with moderate to severe OSA, recruited from University Hospitals Cleveland Medical Center (UH) and Yale New Haven Health (YNHH). Participants will be randomized to bexagliflozin 20 mg once daily or matching placebo in addition to standard routine clinical care for both groups for 6 months. At baseline and at study end, participants will undergo measurements of anatomic traits using MRI imaging, critical closing pressure, blood-based biomarkers of dysfunctional adiposity, non-anatomic physiologic trait polysomnographic phenotyping, morning neck circumference, clinical measures of sleep apnea severity (apnea hypopnea index (AHI), oxygen desaturation index (ODI), % time with O2sat \< 90% (T90)), sleep arousal index (AI)), and measures of sleep deficiency, to evaluate the effects of SGLT2i on the measured phenotypes.

Вмешательства

• Препарат Bexagliflozin 20 mg
  15mg once daily
• Препарат Placebo
  matching placebo once daily

Первичные конечные точки

• Change in Apnea hypopnea index (AHI) measured by full ambulatory polysomnography (aPSG) [Срок оценки: Baseline and 6 months]

Вторичные конечные точки (12)

• Change in Neck and body fat and lean volume by MRI [Срок оценки: Baseline and 6 months]
• Change in Airway caliber by MRI [Срок оценки: Baseline and 6 months]
• Change in Critical closing pressure (Pcrit)/normal ventilatory drive (Vpass) by aPSG [Срок оценки: Baseline and 6 months]
• Change in neck circumference [Срок оценки: Baseline and 6 months]
• Change in Oxygen desaturation index (ODI) measured by aPSG [Срок оценки: Baseline and 6 months]
• Change in Sleep arousal index (ArI) measured by aPSG [Срок оценки: Baseline and 6 months]
• Change in Insomnia Severity Index (ISI) [Срок оценки: Baseline, 3 months and 6 months]
• Change in Sleep Quality measured by Pittsburgh Sleep Quality Index Form [Срок оценки: Baseline, 3 months and 6 months]
• Change in Reduced Morningness Eveningness Questionnaire (MEQ) [Срок оценки: Baseline, 3 months and 6 months]
• Change in Regulatory Satisfaction Alertness Timing Efficiency Duration (RU-SATED) [Срок оценки: Baseline, 3 months and 6 months]
• Change in Sleep Deprivation Questionnaire (SDQ) [Срок оценки: Baseline, 3 months and 6 months]
• Change in STOP - Bang questionnaire [Срок оценки: Baseline, 3 months and 6 months]

Критерии участия

Критерии включения

• Able to provide informed consent and stated willingness to comply with all study procedures and availability for the duration of the study
• Overweight or obese (body mass index 25-40 kg/m2)
• Clinically confirmed diagnosis of obstructive sleep apnea by one of the following methods:

a. Polysomnography: AHI ≥15/hour sleep or b. Home sleep apnea testing: Respiratory event index (REI) ≥15/hour sleep

• AHI: apnea-hypopnea index (apneas + hypopneas / total sleep time in hours)

Критерии исключения

An individual who meets any of the following criteria will be excluded from participation in this study:

• Known non-OSA related conditions associated with sleep disordered breathing (e.g., central disorder of hypersomnolence, neurological, neuromuscular, or pulmonary disorder)
• Use of sleep-inducing medications (e.g. benzodiazepines, opiates, barbiturates)
• Type 1 diabetes mellitus
• History of diabetic ketoacidosis
• Known hypersensitivity reaction to bexagliflozin or any of its constituents or any contraindication to bexagliflozin use
• Severe, recurrent urinary tract or genital mycotic infections
• eGFR<30mL/min/1.73m2 at time of or within 4 weeks of enrollment in the study
• Unable to complete/tolerate magnetic resonance imaging (MRI) due to severe claustrophobia or metallic implants.
• Language barrier, mental incapacity, unwillingness or inability to understand.
• Females of childbearing potential who are pregnant, breast-feeding or intend to become pregnant.
• Currently or planning to take a SGLT2i prior to or during enrollment in the study
• Currently or planning to follow a ketogenic diet pattern ("keto diet) prior to or during enrollment in the study
• Currently or planning to follow an active weight loss program (including but not limited to use of supplements, medications, or surgery) prior to or during enrollment in the study
• Currently or planning to follow an intermittent fasting diet plan prior to or during enrollment in the study
• Currently or planning to take a GLP-1 receptor agonist prior to or during enrollment in the study .
• Existing lower limb ulcer (due to diabetes or any cause)
• Existing severe peripheral arterial disease with intermittent claudication and/or prior lower limb revascularization procedure
• Concomitant administration of UGT inducers
• Severe liver disease

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 2 центра

• Yale New Haven Health — New Haven
• University Hospitals Cleveland Medical Center — Cleveland

Идентификаторы

NCT: NCT05612594 · 2000033371

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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