Semaglutide to Reduce Atrial Fibrillation Burden

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

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 Overview

• Status: Suspended
• Conditions: Obesity; Overweight; Atrial Fibrillation
• Intervention / Treatment: Drug: Semaglutide; Drug: Placebo

• Study Type: Interventional
• Enrollment (Anticipated): 132
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94121
      • Veterans Affairs Medical Center San Francisco

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo and intake visit for VA MOVE
Experimental: Semaglutide	Drug: Semaglutide; 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: San Francisco Veterans Affairs Medical Center

Study record dates

Study Major Dates

• Study Start (Anticipated): May 1, 2023
• Primary Completion (Anticipated): May 1, 2027
• Study Completion (Anticipated): May 1, 2028

Study Registration Dates

• First Submitted: January 14, 2022
• First Submitted That Met QC Criteria: January 14, 2022
• First Posted (Actual): January 26, 2022

Study Record Updates

• Last Update Posted (Actual): October 27, 2022
• Last Update Submitted That Met QC Criteria: October 24, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Keywords: atrial fibrillation; weight loss; lifestyle modification
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Body Weight; Arrhythmias, Cardiac; Atrial Fibrillation; Overweight
• Other Study ID Numbers: SFVAEP1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No