Clinical trial NCT05612594: Adipose Dysfunction, Imaging, Physiology, and Outcomes With Sodium Glucose Cotransporter 2 Inhibitor (SGLT2i) for Sleep Apnea: The ADIPOSA Study
Official title: Adipose Dysfunction, Imaging, Physiology, and Outcomes With SGLT2i's for Sleep Apnea: The ADIPOSA Study
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Sleep Apnea
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Case Western Reserve University
First posted: 2022-11-10
Enrollment: 164
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

* 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)

Exclusion Criteria:

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

Primary outcomes:
measure: Change in Apnea hypopnea index (AHI) measured by full ambulatory polysomnography (aPSG)
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Change in Neck and body fat and lean volume by MRI
timeFrame: Baseline and 6 months
measure: Change in Airway caliber by MRI
timeFrame: Baseline and 6 months
measure: Change in Critical closing pressure (Pcrit)/normal ventilatory drive (Vpass) by aPSG
timeFrame: Baseline and 6 months
measure: Change in neck circumference
timeFrame: Baseline and 6 months
measure: Change in Oxygen desaturation index (ODI) measured by aPSG
timeFrame: Baseline and 6 months
measure: Change in Sleep arousal index (ArI) measured by aPSG
timeFrame: Baseline and 6 months
measure: Change in Insomnia Severity Index (ISI)
timeFrame: Baseline, 3 months and 6 months
measure: Change in Sleep Quality measured by Pittsburgh Sleep Quality Index Form
timeFrame: Baseline, 3 months and 6 months
measure: Change in Reduced Morningness Eveningness Questionnaire (MEQ)
timeFrame: Baseline, 3 months and 6 months
measure: Change in Regulatory Satisfaction Alertness Timing Efficiency Duration (RU-SATED)
timeFrame: Baseline, 3 months and 6 months
measure: Change in Sleep Deprivation Questionnaire (SDQ)
timeFrame: Baseline, 3 months and 6 months
measure: Change in STOP - Bang questionnaire
timeFrame: Baseline, 3 months and 6 months
measure: Change inThe Sleep Apnea Quality of Life Index (SAQLI).
timeFrame: Baseline, 3 months and 6 months
measure: Change in The Epworth Sleepiness Scale (ESS)
timeFrame: Baseline, 3 months and 6 months
measure: Change in height.
timeFrame: Baseline and 6 months
measure: Change in weight.
timeFrame: Baseline and 6 months
measure: Change in body mass index (BMI)
timeFrame: Baseline and 6 months
measure: Change in Waist circumference
timeFrame: Baseline and 6 months
measure: Change in hip circumference
timeFrame: Baseline and 6 months
measure: Change in sleep walking periods measured using Wrist-wearable actigraphy
timeFrame: Baseline, 3 months and 6 months
measure: Change in 24 hour ambulatory average systolic blood pressure
timeFrame: Baseline, 3 months and 6 months
measure: Change in 24 hour ambulatory average diastolic blood pressure
timeFrame: Baseline, 3 months and 6 months
measure: Change in 24 hour ambulatory blood pressure variability
timeFrame: Baseline, 3 months and 6 months
measure: Change in 24 hour ambulatory nighttime blood pressure dipping
timeFrame: Baseline, 3 months and 6 months
measure: Change in Vdrive/Loop gain by aPSG
timeFrame: Baseline and 6 months
measure: Vdrive/Arousal threshold (ArTH) by aPSG
timeFrame: Baseline and 6 months
measure: Vdrive/Pharyngeal muscle compensation (Mresp) by aPSG
timeFrame: Baseline and 6 months
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Health
state: Connecticut
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
Study officials:
affiliation: Yale University
name: Henry K Yaggi, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: Case Western Reserve University School of Medicine
name: Ian J Neeland, M.D.
role: PRINCIPAL_INVESTIGATOR
References: