Overview

Semaglutide for the Reduction of Arrhythmia Burden in Overweight AF Patients

Status:
Not yet recruiting
Trial end date:
2024-11-01
Target enrollment:
0
Participant gender:
All
Summary
The purpose of this pilot study is to assess the feasibility of a double-blind, randomized placebo-controlled trial of semaglutide 2.4 mg subcutaneously once weekly on top of standard care compared to standard care alone.
Phase:
Phase 3
Accepts Healthy Volunteers?
No
Details
Lead Sponsor:
Axel Brandes
Collaborators:
Herlev and Gentofte Hospital
Hillerod Hospital, Denmark
Hospital of South West Jutland
Svendborg Hospital
Criteria
Inclusion Criteria:

- Signed informed consent before any study-related activity

- ≥ 18 years of age at the time of signing informed consent

- Body mass index (BMI) ≥ 30 kg/m2

- Body mass index (BMI) ≥ 27 kg/m2 and at least 1 concomitant cardiometabolic risk
factor (hypertension, dyslipidemia, or obstructive sleep apnea)

- Symptomatic paroxysmal or early persistent atrial fibrillation (Paroxysmal AF: Self-
terminating, in most cases within 48 hours up to 7 days. AF episodes that are
cardioverted within 7 days with a documented 12 lead ECG showing sinus rhythm within
the last 12 months; early persistent AF: AF episodes lasting longer than 7 days,
including episodes that are terminated by cardioversion, either with drugs or by
direct current cardioversion, after 7 days or more. Early persistent AF in this trial
is defined as persistent AF with first-time electrical cardioversion (ECV) or a
maximum of 1 previous ECVs.)

Exclusion Criteria:

- General exclusion criteria

- Age ≥75 years

- History of type 1 or 2 diabetes (history of gestational diabetes is allowed)

- Known or suspected hypersensitivity to study medication or related products

- Treatment with GLP-1 receptor agonists within the last 3 months before
randomisation

- Treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors

- Alcohol/drug abuse

- Pregnant or breastfeeding women

- Fertile women not using chemical (tablet/pill, depot injection of progesterone,
sub- dermal gestagen implantation, hormonal vaginal ring or transdermal hormonal
patch) or mechanical (spirals) contraceptives

- Active malignancy, unless in complete remission for ≥5 years

- Family or personal history of multiple endocrine neoplasia type 2 (MEN2) or
familial medullary thyroid carcinoma (FMTC)

- Personal history of non-familial medullary thyroid carcinoma

- Inflammatory bowel diseases

- Acute or chronic pancreatitis

- Obesity induced by other endocrinologic disorders (e.g. Cushing's Syndrome)

- Current history of treatment with medications that may cause significant weight
gain, within the last 3 months before screening, including systemic
corticosteroids (except for a short course of treatment, i.e. 7-10 days),
tri-cyclic antidepressants, atypical antipsychotic and mood stabilizers (e.g.
imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine,
thioridazine, clozapine, olanzapine, valproic acid and its derivatives, and
lithium)

- Diet attempts using herbal supplements or over-the-counter medications within 3
months before screening

- Current participation (or within the last 3 months) in an organised weight
reduction programme or currently using or used within 3 months before screening:
pramlintide, sibutramine, orlistat, zonisamide, topiramate, phentermine (either
by prescription or as part of a clinical trial)

- Severe chronic obstructive pulmonary disease

- Uncontrolled treated/untreated hypertension (systolic >180 mmHg and/or diastolic
>105 mmHg)

- Previous or planned surgical treatment for obesity

- Life expectancy <2.5 years

- Other concomitant disease or treatment that according to the investigator's
assessment makes the subject unsuitable for study participation

- Participation in any other clinical intervention trial

- Previous participation in the SOCRATES-AF pilot study

- Inability to sign informed consent

- Exclusion criteria related to a cardiac condition

- Previous or planned AF ablation

- Previous use of continuous prophylactic class I or III antiarrhythmic drugs

- Long-standing persistent or permanent AF

- Overall clinical history of persistent AF ≥5 years

- ECG suggestive of malignant ventricular arrhythmia

- Prolonged corrected QT-interval (>500 ms), unless caused by bundle branch block

- Myocardial infarction (MI) within the last 3 months before screening

- Coronary revascularization within the last 3 months before screening

- Planned coronary revascularisation

- Cardiac surgery within the last 12 months before screening

- Obstructive hypertrophic cardiomyopathy

- Clinically significant valvular heart disease

- Left ventricular (LV) dysfunction (HFrEF with left ventricular ejection fraction
(LVEF) <45%) unless elicited by AF

- Hospitalization due to decompensated heart disease within 30 days prior to
randomization

- Congestive heart failure (NYHA class IV)

- Current myocardial or pericardial infection

- Permanent pacemaker (PM) in use or implantable cardioverter defibrillator (ICD)

- Patient cannot be prescribed non-vitamin K oral anticoagulant (NOAC)

- perform physical exercise for medical or personal reasons

- Exclusion criteria based on laboratory abnormalities

- Liver disease with increased plasma alanine aminotransferase (ALAT) levels of
more than three times the upper limit of normal

- Renal dysfunction (eGFR <30 ml/min), dialysis or kidney transplant

- Clinically manifest thyroid dysfunction requiring therapy. After successful
treatment of thyroid dysfunction, subjects may be enrolled, when thyroid function
is controlled.

- HbA1c >6.5% measured at screening