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Liraglutide Effect in Atrial Fibrillation (LEAF)

Primary Purpose

Atrial Fibrillation

Status

Active

Phase

Phase 4

Locations

United States

Study Type

Interventional

Intervention

Liraglutide

RFM

Anti Arrhythmics

Afib Catheter Ablation

About this trial

This is an interventional treatment trial for Atrial Fibrillation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

University of Miami

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Risk Factor Modification (RFM)

RFM plus Liraglutide

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Change in size of Left Atrial Epicardial Adipose Tissue (LAEAT)

As assessed via multi detector cardiac computer tomography (MD-CT)

Secondary Outcome Measures

Change in size of Epicardial Adipose Tissue (EAT) thickness

As assessed via echocardiography

Change in atrial function

As assessed via echocardiography

Change in atrial size

As assessed via echocardiography

Change in C-Reactive Protein (CRP) value

Serial changes in biomarkers of inflammation

Change in Interleukin-6 (IL-6)

Serial changes in biomarkers of inflammation

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

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

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

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

Full Information

NCT ID

NCT03856632

First Posted

February 25, 2019

Last Updated

April 18, 2023

Sponsor

University of Miami

1. Study Identification

Unique Protocol Identification Number

NCT03856632

Brief Title

Liraglutide Effect in Atrial Fibrillation

Acronym

LEAF

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

April 2023

Overall Recruitment Status

Active, not recruiting

Study Start Date

March 18, 2019 (Actual)

Primary Completion Date

December 31, 2024 (Anticipated)

Study Completion Date

December 31, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Miami

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Atrial Fibrillation

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 4

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Randomized

Enrollment

60 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Risk Factor Modification (RFM)

Arm Type

Active Comparator

Arm Description

Arm Title

RFM plus Liraglutide

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

Liraglutide

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

RFM

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Anti Arrhythmics

Intervention Description

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.

Intervention Type

Procedure

Intervention Name(s)

Afib Catheter Ablation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in size of Left Atrial Epicardial Adipose Tissue (LAEAT)

Description

As assessed via multi detector cardiac computer tomography (MD-CT)

Time Frame

Baseline, 3 months (prior to ablation)

Secondary Outcome Measure Information:

Title

Change in size of Epicardial Adipose Tissue (EAT) thickness

Description

As assessed via echocardiography

Time Frame

Baseline, 3 months (prior to ablation), 1 year post-ablation

Title

Change in atrial function

Description

As assessed via echocardiography

Time Frame

Baseline, 1 year post ablation

Title

Change in atrial size

Description

As assessed via echocardiography

Time Frame

Baseline, 1 year post ablation

Title

Change in C-Reactive Protein (CRP) value

Description

Serial changes in biomarkers of inflammation

Time Frame

Baseline, 1 year post ablation

Title

Change in Interleukin-6 (IL-6)

Description

Serial changes in biomarkers of inflammation

Time Frame

Baseline, 1 year post ablation

Title

Correlation of CRP expression in blood from left atrium to peripheral plasma

Description

At the same time point, blood will be collected directly from left atrium and peripheral vessel during the ablation procedure and compared

Time Frame

During the catheter ablation procedure

Title

Correlation of IL-6 expression in blood from left atrium to peripheral plasma

Description

At the same time point blood, will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared

Time Frame

During the catheter ablation procedure

Title

Correlation of plasminogen activator inhibitor (PAI-1), matrix metalloproteinase-2 (MMP2), Tissue inhibitor of metalloproteinase 2 (TIMP-2)

Description

At the same time point, blood will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared

Time Frame

During the catheter ablation procedure

Title

Correlation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP)

Description

At the same time point, blood will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared

Time Frame

During the catheter ablation procedure

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Jeffrey Goldberger, MD

Organizational Affiliation

University of Miami

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Miami

City

Miami

State/Province

Florida

ZIP/Postal Code

33136

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

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Liraglutide Effect in Atrial Fibrillation

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