Atrial fibrillation (AF) is the most common arrhythmia worldwide. AF is associated with obesity and the co-morbidities of obesity, including hypertension and obstructive sleep apnea (OSA) which increase left atrial (LA) size and decrease LA function. Semaglutide, a Glucagon-like peptide receptor 1 agonist (GLP-1 RA), is currently approved by the Food and Drug Administration for weight loss for individuals with and without diabetes. The effects of pharmacologic weight loss with Semaglutide on AF are unknown. The investigators plan on conducting a randomized controlled trial of semaglutide versus placebo in individuals with paroxysmal or early persistent AF (\>10% AF burden on ambulatory monitoring, a previous electrical cardioversion, or AF lasting ≥ 7 days but \< 3 months who have a body mass index ≥ 27.0 kg/m2. The trial will last for 52 weeks. The primary outcome will be the change in AF burden for 2 weeks, immediately before starting the medication or placebo to two weeks starting at week 50, as determined by an implantable loop recorder or two week ambulatory Additional outcomes will be change in epicardial adipose tissue as determined by chest/abdomen/pelvis computed tomography scan at enrollment and at week 52, change in apnea-hypopnea index from baseline sleep study to week 52 sleep study, change in LA longitudinal strain from baseline echocardiogram to echocardiogram at 52 weeks, and change on symptom surveys.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
132
weekly Semaglutide (increased from starting dose of 0.25 mg at four-week intervals (0.5 mg, 1.0 mg, 1.7 mg) to a target dose of 2.4 mg) for 52 weeks with intake visit for the VA MOVE program
Matching placebo and intake visit for VA MOVE
Veterans Affairs Medical Center San Francisco
San Francisco, California, United States
Atrial fibrillation burden
Change in AF burden from the two weeks before starting Semaglutide or placebo to the last two weeks of therapy (starting at week 50). AF burden will be assessed as percent of time in AF for two weeks on an implantable loop recorder. If the patient declines implantable loop recorder placement, an ambulatory 2-week monitor will be used instead.
Time frame: 52 weeks
Epicardial adipose tissue
Change in epicardial adipose tissue on non-contrast chest/abdomen CT scans from baseline and week 52
Time frame: 52 weeks
Sleep apnea
Change in apnea-hypopnea index from baseline sleep study to sleep study at week 52
Time frame: 52 weeks
Left atrial function
The change in LA longitudinal strain from the baseline echocardiogram to the echocardiogram at 52 weeks.
Time frame: 52 weeks
Weight change
From baseline to week 52
Time frame: 52 weeks
Adherence and Adverse Events
From baseline to week 52
Time frame: 52 weeks
Participation in VA MOVE
assess participation
Time frame: 52 weeks
Change in AF burden for four weeks
Change in AF burden for 4 weeks before starting the medication to weeks 48-52.
Time frame: 52 weeks
Fat depots
change in pericardial, abdominal (visceral and subcutaneous) and hepatic adipose tissue
Time frame: 52 weeks
Left atrial size and function
Changes in LA size and function between baseline and week 52 echocardiograms: LA volume as assessed using the biplane disk summation method, LA reservoir strain, LA conduit strain, and LA booster pump strain will be assessed as secondary outcomes
Time frame: 52 weeks
Quality of life on Healthcare Quality of Life surverys
Quality of life on the Short-Form 36 survey and the AF symptoms and severity checklist, which will be completed at baseline and at week 52
Time frame: 52 weeks
Change in C-reactive Protein (CRP)
Change in the biomarker CRP between baseline and week 52
Time frame: 52 weeks
Blood pressure
Changes in blood pressure and blood pressure medication use between baseline and week 52 will be assessed at those visits.
Time frame: 52 weeks
Change in Interleukin-6 (IL-6)
Change in the biomarker IL- 6 between baseline and week 52
Time frame: 52 weeks
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