Semaglutide for Metabolic Intervention and Adipose Loss to Treat Atrial Fibrillation

NCT06499857 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: IRB23-0889
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 2

Brief Summary

The goal of the study is to learn how a weight loss medication called semaglutide, which is used to treat obesity, in addition to standard AF treatment might affect AF, atrial fibrillation severity, and whether it changes the risk of atrial fibrillation recurring after standard AF treatments.

Conditions

Overweight or Obesity; Atrial Fibrillation

Outcome Measures

Primary Outcomes (2)

• Time to first AF event detected by routine outpatient monitoring

  Defined by length of time detected by routine outpatient monitoring (Holter, mobile telemetry, or implantable loop recorder).

  Baseline to Week 68

• Change from baseline in AF burden detected by routine outpatient monitoring.

  Defined as the percentage of time spent in atrial fibrillation as detected by routine outpatient monitoring (Holter, mobile telemetry, or implantable loop recorder).

  Baseline to Week 68

Secondary Outcomes (16)

• Weight loss

  Baseline to Week 68

• Change in waist circumference

  Baseline to Week 68

• Change in epicardial and/or pericardial adipose tissue volume

  Baseline to Week 68

• Change in left and right ventricular size (mass)

  Baseline to Week 68

• Change in left and right ventricular size (volume)

  Baseline to Week 68

Study Arms (2)

Semaglutide

ACTIVE COMPARATOR

Participants will have a 2 in 3 chance of receiving semaglutide (2.4 mg).

Drug: Semaglutide

Placebo

PLACEBO COMPARATOR

Participants will have a 1 in 3 chance of receiving placebo.

Drug: Placebo

Interventions

Semaglutide DRUG

3ml pen-injector containing semaglutide 3.0mg/ml solution for subcutaneous use.

Semaglutide

Placebo DRUG

3ml pen-injector containing placebo solution for subcutaneous use.

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-75 years
• BMI greater than or equal to 30 kg/m2
• Paroxysmal AF or persistent AF, in whom catheter ablation (CA) for AF is expected within 1 year (A group) or in whom catheter ablation is NOT expected within 1 year (M group)
• Ability to provide informed consent before any trial-related activities.
• Patients with type 2 diabetes mellitus (T2DM) will be included:
• If HbA1c (glycated hemoglobin) is less than or equal to 10 %
• If the subject is taking basal insulin only or oral hypoglycemic agents or a combination of those.
• Patients on SGLT2-inhibitors and TZDs (Thiazolidinedione) will be included if they have been on a stable dose of these medications for at least 6 months
• The following protocol will be adopted to adjust insulin secretagogues (sulfonylureas or meglitinides) and insulin during the study (adapted from the Look Ahead Study).
• Patients will be asked to check their blood glucose (BG) 4 x day (before meals and at bed time) during the dose escalation and dose stabilization phases (weeks 0 to 20) and recommendation of dose adjustments will be immediately sent to their treating physician according to the dose adjustment scale below:
• blood sugars \<100 mg/dl- reduce meds \[insulin secretagogues (sulfonylureas or meglitinides) and basal insulin\] by 0-50 %
• blood sugars 80-100 mg/dl- reduce meds \[insulin secretagogues (sulfonylureas or meglitinides) and basal insulin\] by 25-75%
• blood sugars \<80 mg/dl \> 2 x week or severe hypoglycemia or symptomatic hypoglycemia- reduce meds \[insulin secretagogues (sulfonylureas or meglitinides) and basal insulin\] by 50-100 %
• Randomization to treatment (active and placebo) will be stratified to balance patients with T2DM across the study arms. After completion of the trial a prespecified subgroup analysis of the patients enrolled affected by T2DM will be performed.
• For women of child-bearing potential, use of appropriate contraception will be required.

You may not qualify if:

• Current use of GLP-1 RA (glucagon-like peptide receptor agonists) or DPP4 (Dipeptidyl peptidase-4)-inhibitors or use within the last 90 days prior to screening
• Current antiobesity medication use or use within the last 90 days prior to screening
• A self-reported change in body weight of \> 5 kg (11 lb.) within 30 days before screening
• History of bariatric surgery
• History of type I diabetes mellitus
• Current use of prandial insulin
• Hospitalization for unstable angina, or TIA (Transient ischemic attack) \< 30 days prior to screening
• Pulmonary embolism \< 90 days before screening
• MI (myocardial infarction), stroke, etc. \< 90 months prior to screening
• Uncontrolled thyroid disease: TSH (Thyroid-stimulating hormone) \> 10.0 mIU/L (Milli-international Units Per Liter) or \< 0.4 mIU/L (Milli-international Units Per Liter) at screening
• Active malignancy
• Active enrollment in another investigational study that includes any kind of intervention
• The receipt of any investigational drug within 90 days prior to this trial.
• Inability to comply with study procedures
• Acute pancreatitis \< 180 days before screening

Sponsors & Collaborators

• University of Chicago: lead

Study Sites (2)

The University of Arizona College of Medicine- Phoenix

Phoenix, Arizona, 85004, United States

NOT YET RECRUITING

University of Chicago

Chicago, Illinois, 60637, United States

RECRUITING

MeSH Terms

Conditions

Overweight; Obesity; Atrial Fibrillation

Interventions

semaglutide

Condition Hierarchy (Ancestors)

Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes

Study Officials

• Silvana Pannain, MD

  University of Chicago

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Silvana Pannain, MD

CONTACT

773-702-3275; spannain@bsd.uchicago.edu

Andrew Beaser, MD

CONTACT

773-702-9324; abeaser@bsd.uchicago.edu

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel Assignment Prospective, Randomized and Blinded

Study Record Dates

• First Submitted: April 24, 2024
• First Posted: July 15, 2024
• Study Start: April 14, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2028
• Last Updated: November 14, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)