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SEMINAL-AF
RecruitingPhase 3Semaglutide for Metabolic Intervention and Adipose Loss to Treat Atrial Fibrillation
Lead sponsor
Asset
Semaglutide
Subcutaneous · GLP-1 agonist
Listed sites
2
Recruiting sites
1
Enrollment
200
estimated
Study population
Atrial fibrillation, Obesity / overweight
Key I/E criteria
•BMI ≥30•HbA1c ≤10%
Primary endpoints
•Atrial-fibrillation composite•AF burden detected by routine outpatient monitoring
Footprint
Where this trial recruits
Site locations as reported to ClinicalTrials.gov. Site count is not enrollment count; per-site enrollment is not available from source.
Identifiers
Registered as
Timeline
Milestones
Assets
Investigational agents
Study populations
Who this study enrolls
Eligibility
Who can enroll
Inclusion criteria
1. Age 18-75 years
2. BMI greater than or equal to 30 kg/m2
3. 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)
4. Ability to provide informed consent before any trial-related activities.
5. Patients with type 2 diabetes mellitus (T2DM) will be included:
1. If HbA1c (glycated hemoglobin) is less than or equal to 10 %
2. If the subject is taking basal insulin only or oral hypoglycemic agents or a combination of those.
3. 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
4. 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:
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.
In patients that are prescribed amiodarone, standard care practices will be implemented to evaluate for liver and thyroid side effects with baseline liver and thyroid function tests via blood draw and evaluation every 6 months.
Exclusion criteria
1. 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
2. Current antiobesity medication use or use within the last 90 days prior to screening
3. A self-reported change in body weight of > 5 kg (11 lb.) within 30 days before screening
4. History of bariatric surgery
5. History of type I diabetes mellitus
6. Current use of prandial insulin
7. Hospitalization for unstable angina, or TIA (Transient ischemic attack) < 30 days prior to screening
8. Pulmonary embolism < 90 days before screening
9. MI (myocardial infarction), stroke, etc. < 90 months prior to screening
10. 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
11. Active malignancy
12. Active enrollment in another investigational study that includes any kind of intervention
13. The receipt of any investigational drug within 90 days prior to this trial.
14. Inability to comply with study procedures
15. Acute pancreatitis < 180 days before screening
16. History or presence of chronic pancreatitis
17. CKD (Chronic Kidney Disease) stage 4 (GFR <30 ml/min)
18. A personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
19. A prior serious hypersensitivity reaction to semaglutide or to any of the excipients in WEGOVY
20. Chronic inflammatory conditions requiring immunosuppression and/or on glucocorticoids
21. Previous participation in this trial (received at least one dose of study drug or placebo)
22. Pregnant, breast-feeding or planning pregnancy
Endpoints (18)
What's being measured
Protocol endpoints and posted registry outcome measures, grouped into outcome categories. Composite endpoints show their component event types. Standard codes (LOINC, SNOMED CT) are shown where available.
Coverage by outcome category
Cardiovascular outcomes
1 endpointTime to first AF event detected by routine outpatient monitoring
Time frame:Baseline to Week 68
Atrial-fibrillation composite
time to event, event
Weight & body composition
4 endpointsWeight loss
Time frame:Baseline to Week 68
Body weight, absolute change (kg)
change from baseline, improvement
Change in waist circumference
Time frame:Baseline to Week 68
Waist circumference, change
change from baseline, improvement
Change in epicardial and/or pericardial adipose tissue volume
Time frame:Baseline to Week 68
change from baseline, improvement
Changes in Body mass composition
Time frame:Baseline to Week 68
Total fat mass
percent change from baseline, improvement
Glycemic / diabetes
1 endpointChanges in Metabolic effects
Time frame:Baseline to Week 68
HbA1c, change
change from baseline, improvement
LOINC 4548-4
Heart failure
1 endpointLeft atrial and myocardial stress
Time frame:Baseline to Week 68
NT-proBNP, change
change from baseline, improvement
Cardiometabolic biomarkers
2 endpointsChange in sympathetic activity and in circulating cytokines and adipokines
Time frame:Baseline to Week 68
change from baseline, improvement
Change in Autonomic tone as determined by heart rate variability
Time frame:Baseline to Week 68
change from baseline, improvement
Patient-reported / QoL
1 endpointChanges from baseline through Week 68 of novel Patient Reported Outcome Assessment.
Time frame:Baseline to Week 68
change from baseline, improvement
Other (unclassified)
8 endpointsChange from baseline in AF burden detected by routine outpatient monitoring.
Time frame:Baseline to Week 68
percent change from baseline, improvement
Change in left and right ventricular size (mass)
Time frame:Baseline to Week 68
change from baseline, descriptive
Change in left and right ventricular size (volume)
Time frame:Baseline to Week 68
change from baseline, descriptive
Change in left and right ventricular function (ejection fraction)
Time frame:Baseline to Week 68
change from baseline, improvement
Change in left ventricular strain
Time frame:Baseline to Week 68
change from baseline, improvement
Change in left ventricular diastolic parameters
Time frame:Baseline to Week 68
change from baseline, descriptive
Change in LV (left ventricular) myocardial fibrosis
Time frame:Baseline to Week 68
change from baseline, improvement
Changes from baseline through Week 68 of Atrial conduction times
Time frame:Baseline to Week 68
change from baseline, descriptive
Provenance
Sources
Trial facts come from public ClinicalTrials.gov records. Endpoint categories are Delfa's classification of those records, not a ClinicalTrials.gov field. All figures reflect the July 1, 2026 snapshot.