Semaglutide to Reduce Atrial Fibrillation Burden

• ClinicalTrials.gov Identifier: NCT05209165
• Recruitment Status: Not yet recruiting
• First Posted: January 26, 2022
• Last Update Posted: February 9, 2022
• Sponsor: San Francisco Veterans Affairs Medical Center
• Information provided by (Responsible Party): Adam Oesterle, San Francisco Veterans Affairs Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Atrial Fibrillation; Obesity; Overweight	Drug: Semaglutide; Drug: Placebo	Phase 4

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 132 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Semaglutide as Treatment of Overweight and Obese Individuals to Reduce Atrial Fibrillation Burden
• Estimated Study Start Date: May 2022
• Estimated Primary Completion Date: May 2027
• Estimated Study Completion Date: May 2028

Arms and Interventions

Arm	Intervention/treatment
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
Placebo Comparator: Placebo	Drug: Placebo; Matching placebo and intake visit for VA MOVE

Outcome Measures

Primary Outcome Measures :

1. Atrial fibrillation burden [ Time Frame: 52 weeks ]
   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.

Secondary Outcome Measures :

1. Epicardial adipose tissue [ Time Frame: 52 weeks ]
   Change in epicardial adipose tissue on non-contrast chest/abdomen CT scans from baseline and week 52
2. Sleep apnea [ Time Frame: 52 weeks ]
   Change in apnea-hypopnea index from baseline sleep study to sleep study at week 52
3. Left atrial function [ Time Frame: 52 weeks ]
   The change in LA longitudinal strain from the baseline echocardiogram to the echocardiogram at 52 weeks.
4. Weight change [ Time Frame: 52 weeks ]
   From baseline to week 52
5. Adherence and Adverse Events [ Time Frame: 52 weeks ]
   From baseline to week 52
6. Participation in VA MOVE [ Time Frame: 52 weeks ]
   assess participation
7. Change in AF burden for four weeks [ Time Frame: 52 weeks ]
   Change in AF burden for 4 weeks before starting the medication to weeks 48-52.
8. Fat depots [ Time Frame: 52 weeks ]
   change in pericardial, abdominal (visceral and subcutaneous) and hepatic adipose tissue
9. Left atrial size and function [ Time Frame: 52 weeks ]
   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
10. Quality of life on Healthcare Quality of Life surverys [ Time Frame: 52 weeks ]
    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
11. Change in C-reactive Protein (CRP) [ Time Frame: 52 weeks ]
    Change in the biomarker CRP between baseline and week 52
12. Blood pressure [ Time Frame: 52 weeks ]
    Changes in blood pressure and blood pressure medication use between baseline and week 52 will be assessed at those visits.
13. Change in Interleukin-6 (IL-6) [ Time Frame: 52 weeks ]
    Change in the biomarker IL- 6 between baseline and week 52

Eligibility Criteria

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

Criteria

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

Contacts and Locations

Contacts

Contact: Adam Oesterle, MD; 4152214810 ext 24365; adam.oesterle@va.gov

Locations

United States, California

Veterans Affairs Medical Center San Francisco

San Francisco, California, United States, 94121

Contact: Adam Oesterle, M.D. 415-221-4810 ext 24365 adam.oesterle@va.gov

Sponsors and Collaborators

San Francisco Veterans Affairs Medical Center

More Information

• Responsible Party: Adam Oesterle, Principal Investigator, San Francisco Veterans Affairs Medical Center
• ClinicalTrials.gov Identifier: NCT05209165
• Other Study ID Numbers: SFVAEP1
• First Posted: January 26, 2022
• Last Update Posted: February 9, 2022
• Last Verified: January 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Adam Oesterle, San Francisco Veterans Affairs Medical Center:

weight loss; atrial fibrillation; lifestyle modification

Additional relevant MeSH terms:

Atrial Fibrillation; Overweight; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Body Weight