Semaglutide to Reduce Atrial Fibrillation Burden

Study Overview
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Brief Summary
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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.

Official Title
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Semaglutide as Treatment of Overweight and Obese Individuals to Reduce Atrial Fibrillation Burden

Conditions
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Atrial Fibrillation, Obesity, Overweight

Intervention / Treatment
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* Drug: Semaglutide
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years old with a BMI ≥ 27 kg/m2 who have paroxysmal AF with a ≥ 10% burden on ambulatory monitoring or a previous electrical cardioversion or early persistent AF (≥ 7 days, < 3 months) who are willing to attempt rhythm control. Exclusion Criteria: Unable to consent A personal or family history of medullary thyroid carcinoma A personal or family history of multiple endocrine neoplasia syndrome type 2 History of allergic reaction to Semaglutide or any of its components Currently pregnant or planning to become pregnant Currently breastfeeding History of acute pancreatitis History of pancreatic adenocarcinoma Previous or current GLP-1 RA use Previous or current use of alternative pharmacologic weight loss agents (phentermine, diethylpropion, orlistat, phentermine-topiramate, bupropion- naltrexone, gelesis100, or setmelanotide) Unable to tolerate anticoagulation History of bariatric surgery

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semaglutide<br> | Drug: Semaglutide<br>* 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<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Matching placebo and intake visit for VA MOVE<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 52 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Epicardial adipose tissue | Change in epicardial adipose tissue on non-contrast chest/abdomen CT scans from baseline and week 52 | 52 weeks | 
| Sleep apnea | Change in apnea-hypopnea index from baseline sleep study to sleep study at week 52 | 52 weeks | 
| Left atrial function | The change in LA longitudinal strain from the baseline echocardiogram to the echocardiogram at 52 weeks. | 52 weeks | 
| Weight change | From baseline to week 52 | 52 weeks | 
| Adherence and Adverse Events | From baseline to week 52 | 52 weeks | 
| Participation in VA MOVE | assess participation | 52 weeks | 
| Change in AF burden for four weeks | Change in AF burden for 4 weeks before starting the medication to weeks 48-52. | 52 weeks | 
| Fat depots | change in pericardial, abdominal (visceral and subcutaneous) and hepatic adipose tissue | 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 | 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 | 52 weeks | 
| Change in C-reactive Protein (CRP) | Change in the biomarker CRP between baseline and week 52 | 52 weeks | 
| Blood pressure | Changes in blood pressure and blood pressure medication use between baseline and week 52 will be assessed at those visits. | 52 weeks | 
| Change in Interleukin-6 (IL-6) | Change in the biomarker IL- 6 between baseline and week 52 | 52 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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weight loss, atrial fibrillation, lifestyle modification