Liraglutide Effect in Atrial Fibrillation (LEAF)

Novel Medical Adjunctive Therapy to Catheter Ablation For Atrial Fibrillation (AF)

The goal (or purpose) of this study is to evaluate (study) a new way to stabilize (steady) the activity between the fat deposits surrounding the heart and the left atrium.

To reduce the amount of EAT, this study will use a medication called Liraglutide. This medication is known to work on fat deposits and produce weight loss. The investigator is conducting this study to find out if Liraglutide will reduce the fat deposits surrounding the participant's heart, and stabilize (and perhaps reduce or eliminate) atrial fibrillation activity.

Study Overview

• Status: Active, not recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Other: RFM; Drug: Anti Arrhythmics; Procedure: Afib Catheter Ablation; Drug: Liraglutide

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Male and female, age 18 or older
• Persistent AF defined as continuous AF sustained beyond 7 days (or AF with the decision to cardiovert before 7 days of enrollment or Paroxysmal AF defined as recurrent AF (≥2 episodes) that terminates spontaneously within 7 days
• BMI ≥27 kg/m2
• Patient wishes to undergo a catheter ablation procedure for the treatment of atrial fibrillation
• Receiving follow-up care at the University of Miami

Exclusion Criteria:

• Inability to sign an informed consent
• Patients with longstanding persistent atrial fibrillation of more than 3 years
• Prior ablation for atrial fibrillation
• Patients not appropriate candidates for catheter ablation such as those with AF due to acute or chronic precipitating medical conditions, for example, hypothyroidism and hyperthyroidism, significant pulmonary disease, pulmonary embolism, left atrial thrombus, class IV heart failure)
• Patients with a life expectancy <1 year
• Patients with a serious medical condition (for example, recent cancer with chemotherapy or radiation therapy within 4 weeks before entering the study) who have not recovered from adverse events due to agents administered more than 4 weeks earlier.
• Known contraindications to Liraglutide, such as the previous history of pancreatitis or medullary thyroid carcinoma
• Personal or family history of multiple endocrine neoplasias
• Known serious hypersensitivity reaction to Liraglutide
• Patients using, glitazones, sodium-glucose transporters 2 inhibitors (SGLT2i), other GLP-1 analogs, or DPP4 inhibitors
• Type 1 diabetes, defined by American Diabetes Association criteria, history of diabetic ketoacidosis, pancreas or beta-cell transplantation, or diabetes due to pancreatitis or pancreatectomy
• Poorly controlled type 2 diabetes with HbA1c > 10%
• Pregnant women
• Women who are breast-feeding or intend to become pregnant

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Risk Factor Modification (RFM); A structured risk factor modification (RFM) program currently offered to all patients who are overweight or obese undergoing an ablation procedure for atrial fibrillation.The RFM program is already offered through our Center for Atrial Fibrillation and is managed by a nurse practitioner. The RFM program will provide patient teaching and education on weight, fitness,blood pressure control, glucose control, cholesterol, sleep apnea, smoking, and alcohol.	Other: RFM; The program involves weight management and exercise regimen (30 minutes for 2 to 4 times a week), hyperlipidemia management (lifestyle measure changes and initiation of statins and fibrates if necessary), management of obstructive sleep apnea (initiation of Continuous Positive Airway Pressure (CPAP) if necessary), management of hypertension (reduction of salt intake, initiation of Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor blockers (ARB) medications if necessary), diabetes management (lifestyle measure changes, endocrine review and initiation of metformin if necessary) and smoking cessation and alcohol abstinence or reduction. This program will be performed at start of study participation all throughout the follow up period.; Drug: Anti Arrhythmics; The choice of antiarrhythmic drug will be at the discretion of the managing physician, but will generally include either a class IC or class III antiarrhythmic drug. If necessary, and clinically indicated, amiodarone may be used. Therapy will be initiated at the start of study participation and will be discontinued 6-12 weeks after the ablation, as deemed clinically appropriate by the managing electrophysiologist.; Procedure: Afib Catheter Ablation; The procedure will be performed according to usual clinical practice. The primary approach will be antral pulmonary vein isolation (PVI), preferably performed by cryoballoon ablation, though radiofrequency may be used as deemed necessary by the operator for clinical reasons. This will be performed after 3 months of RFM or RFM + Liraglutide program.
Experimental: RFM plus Liraglutide; In addition to RFM, Liraglutide will be administered. Liraglutide is an FDA approved medication used as an adjunct to a reduced-calorie diet and increased physical activity for chronic weight management of obese adults with weight-related comorbid conditions.	Other: RFM; The program involves weight management and exercise regimen (30 minutes for 2 to 4 times a week), hyperlipidemia management (lifestyle measure changes and initiation of statins and fibrates if necessary), management of obstructive sleep apnea (initiation of Continuous Positive Airway Pressure (CPAP) if necessary), management of hypertension (reduction of salt intake, initiation of Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor blockers (ARB) medications if necessary), diabetes management (lifestyle measure changes, endocrine review and initiation of metformin if necessary) and smoking cessation and alcohol abstinence or reduction. This program will be performed at start of study participation all throughout the follow up period.; Drug: Anti Arrhythmics; The choice of antiarrhythmic drug will be at the discretion of the managing physician, but will generally include either a class IC or class III antiarrhythmic drug. If necessary, and clinically indicated, amiodarone may be used. Therapy will be initiated at the start of study participation and will be discontinued 6-12 weeks after the ablation, as deemed clinically appropriate by the managing electrophysiologist.; Procedure: Afib Catheter Ablation; The procedure will be performed according to usual clinical practice. The primary approach will be antral pulmonary vein isolation (PVI), preferably performed by cryoballoon ablation, though radiofrequency may be used as deemed necessary by the operator for clinical reasons. This will be performed after 3 months of RFM or RFM + Liraglutide program.; Drug: Liraglutide; Liraglutide will be administered with a starting dose of 0.6 mg once daily and subsequent increments to 1.2 mg once daily (after at least one week) and to 1.8 mg once daily (after at least a week on 1.2 mg). This will be taken for 3 consecutive months in conjunction with RFM program prior to catheter ablation. Treatment will resume post ablation and will be continue for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in size of Left Atrial Epicardial Adipose Tissue (LAEAT)	As assessed via multi detector cardiac computer tomography (MD-CT)	Baseline, 3 months (prior to ablation)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in size of Epicardial Adipose Tissue (EAT) thickness	As assessed via echocardiography	Baseline, 3 months (prior to ablation), 1 year post-ablation
Change in atrial function	As assessed via echocardiography	Baseline, 1 year post ablation
Change in atrial size	As assessed via echocardiography	Baseline, 1 year post ablation
Change in C-Reactive Protein (CRP) value	Serial changes in biomarkers of inflammation	Baseline, 1 year post ablation
Change in Interleukin-6 (IL-6)	Serial changes in biomarkers of inflammation	Baseline, 1 year post ablation
Correlation of CRP expression in blood from left atrium to peripheral plasma	At the same time point, blood will be collected directly from left atrium and peripheral vessel during the ablation procedure and compared	During the catheter ablation procedure
Correlation of IL-6 expression in blood from left atrium to peripheral plasma	At the same time point blood, will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared	During the catheter ablation procedure
Correlation of plasminogen activator inhibitor (PAI-1), matrix metalloproteinase-2 (MMP2), Tissue inhibitor of metalloproteinase 2 (TIMP-2)	At the same time point, blood will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared	During the catheter ablation procedure
Correlation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP)	At the same time point, blood will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared	During the catheter ablation procedure

Collaborators and Investigators

• Sponsor: University of Miami
• Investigators: Principal Investigator: Jeffrey Goldberger, MD, University of Miami

Study record dates

Study Major Dates

• Study Start (Actual): March 18, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 25, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 27, 2019

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 26, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Glucagon-Like Peptide-1 Receptor Agonists; Liraglutide; Anti-Arrhythmia Agents
• Other Study ID Numbers: 20181182

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No