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SEMINAL-AF

RecruitingPhase 3

Semaglutide for Metabolic Intervention and Adipose Loss to Treat Atrial Fibrillation

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 ≥30HbA1c ≤10%

Primary endpoints

Atrial-fibrillation compositeAF 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

NCT IDNCT06499857
Org study IDIRB23-0889

Timeline

Milestones

Study first posted2024-07-15actual
Study start2025-04-14actual
Last update posted2025-11-14actual
Primary completion2027-12estimated (month precision)
Study completion2028-06estimated (month precision)

Assets

Investigational agents

Study populations

Who this study enrolls

Atrial fibrillationObesity / overweight

Eligibility

Who can enroll

Minimum age18 Years
Maximum age75 Years
SexAll
Healthy volunteersNot accepted

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:

2 blood sugars <100 mg/dl- reduce meds [insulin secretagogues (sulfonylureas or meglitinides) and basal insulin] by 0-50 %
3 blood sugars 80-100 mg/dl- reduce meds [insulin secretagogues (sulfonylureas or meglitinides) and basal insulin] by 25-75%
3 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.

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

Other (unclassified)
8
Weight & body composition
4
Cardiometabolic biomarkers
2
Cardiovascular outcomes
1
Glycemic / diabetes
1
Heart failure
1
Patient-reported / QoL
1

Cardiovascular outcomes

1 endpoint
Primary/protocol endpoint

Time 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 endpoints
Secondary/protocol endpoint

Weight loss

Time frame:Baseline to Week 68

Body weight, absolute change (kg)

change from baseline, improvement

Secondary/protocol endpoint

Change in waist circumference

Time frame:Baseline to Week 68

Waist circumference, change

change from baseline, improvement

Secondary/protocol endpoint

Change in epicardial and/or pericardial adipose tissue volume

Time frame:Baseline to Week 68

change from baseline, improvement

Secondary/protocol endpoint

Changes in Body mass composition

Time frame:Baseline to Week 68

Total fat mass

percent change from baseline, improvement

Glycemic / diabetes

1 endpoint
Secondary/protocol endpoint

Changes in Metabolic effects

Time frame:Baseline to Week 68

HbA1c, change

change from baseline, improvement

LOINC 4548-4

Heart failure

1 endpoint
Secondary/protocol endpoint

Left atrial and myocardial stress

Time frame:Baseline to Week 68

NT-proBNP, change

change from baseline, improvement

Cardiometabolic biomarkers

2 endpoints
Secondary/protocol endpoint

Change in sympathetic activity and in circulating cytokines and adipokines

Time frame:Baseline to Week 68

change from baseline, improvement

Secondary/protocol endpoint

Change in Autonomic tone as determined by heart rate variability

Time frame:Baseline to Week 68

change from baseline, improvement

Patient-reported / QoL

1 endpoint
Secondary/protocol endpoint

Changes from baseline through Week 68 of novel Patient Reported Outcome Assessment.

Time frame:Baseline to Week 68

change from baseline, improvement

Other (unclassified)

8 endpoints
Primary/protocol endpoint/low confidence

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

Time frame:Baseline to Week 68

percent change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in left and right ventricular size (mass)

Time frame:Baseline to Week 68

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in left and right ventricular size (volume)

Time frame:Baseline to Week 68

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in left and right ventricular function (ejection fraction)

Time frame:Baseline to Week 68

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in left ventricular strain

Time frame:Baseline to Week 68

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Change in left ventricular diastolic parameters

Time frame:Baseline to Week 68

change from baseline, descriptive

Secondary/protocol endpoint/low confidence

Change in LV (left ventricular) myocardial fibrosis

Time frame:Baseline to Week 68

change from baseline, improvement

Secondary/protocol endpoint/low confidence

Changes from baseline through Week 68 of Atrial conduction times

Time frame:Baseline to Week 68

change from baseline, descriptive

Provenance

Sources

Trial identity, design, statusClinicalTrials.gov API v2
Snapshot dateJuly 1, 2026
Endpoint classificationDelfa endpoint taxonomy v2 (May 13, 2026)
Results tableno registry results posted yet

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.