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Liraglutide Effect in Atrial Fibrillation (LEAF)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03856632
Recruitment Status : Recruiting
First Posted : February 27, 2019
Last Update Posted : June 18, 2020
Sponsor:
Information provided by (Responsible Party):
Jeffrey Goldberger, University of Miami

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.


Condition or disease Intervention/treatment Phase
Atrial Fibrillation Drug: Liraglutide Other: RFM Drug: Anti Arrhythmics Procedure: Afib Catheter Ablation Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Novel Medical Adjunctive Therapy to Catheter Ablation For Atrial Fibrillation (AF)
Actual Study Start Date : March 18, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Liraglutide

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.
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.

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.




Primary Outcome Measures :
  1. Change in size of Left Atrial Epicardial Adipose Tissue (LAEAT) [ Time Frame: Baseline, 3 months (prior to ablation) ]
    As assessed via multi detector cardiac computer tomography (MD-CT)


Secondary Outcome Measures :
  1. Change in size of Epicardial Adipose Tissue (EAT) thickness [ Time Frame: Baseline, 3 months (prior to ablation), 1 year post-ablation ]
    As assessed via echocardiography

  2. Change in atrial function [ Time Frame: Baseline, 1 year post ablation ]
    As assessed via echocardiography

  3. Change in atrial size [ Time Frame: Baseline, 1 year post ablation ]
    As assessed via echocardiography

  4. Change in C-Reactive Protein (CRP) value [ Time Frame: Baseline, 1 year post ablation ]
    Serial changes in biomarkers of inflammation

  5. Change in Interleukin-6 (IL-6) [ Time Frame: Baseline, 1 year post ablation ]
    Serial changes in biomarkers of inflammation

  6. Correlation of CRP expression in blood from left atrium to peripheral plasma [ Time Frame: During the catheter ablation procedure ]
    At the same time point, blood will be collected directly from left atrium and peripheral vessel during the ablation procedure and compared

  7. Correlation of IL-6 expression in blood from left atrium to peripheral plasma [ Time Frame: During the catheter ablation procedure ]
    At the same time point blood, will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared

  8. Correlation of plasminogen activator inhibitor (PAI-1), matrix metalloproteinase-2 (MMP2), Tissue inhibitor of metalloproteinase 2 (TIMP-2) [ Time Frame: During the catheter ablation procedure ]
    At the same time point, blood will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared

  9. Correlation of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) [ Time Frame: During the catheter ablation procedure ]
    At the same time point, blood will be collected directly from left atrium and the peripheral vessel during the ablation procedure and compared



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female, age 18 or older
  • Persistent atrial fibrillation defined as continuous AF that is sustained beyond 7 days (or atrial fibrillation in which a decision is made to cardiovert the patient prior to 7 days).
  • BMI ≥27 kg/m2
  • Patient wishes to undergo catheter ablation procedure for treatment of atrial fibrillation
  • Receiving follow-up care at the University of Miami

Exclusion Criteria:

  • Inability to sign informed consent
  • Patients with paroxysmal atrial fibrillation and longstanding persistent atrial fibrillation
  • 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 prior to 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 previous history of pancreatitis or medullary thyroid carcinoma
  • Personal or family history of multiple endocrine neoplasia
  • Known serious hypersensitivity reaction to Liraglutide
  • Patients using insulin, sulfonylureas, glitazones, sodium-glucose transporters 2 inhibitors (SGLT2i), other Glucagon-like peptide analogues or dipeptidyl peptidase 4 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
  • Pregnant women
  • Women who are breast-feeding or intend to become pregnant

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03856632


Contacts
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Contact: Carmen M Baez-Garcia, RN 305-243-3845 cbaezgarcia@med.miami.edu
Contact: Barbara Lang, RN 305-243-3845 blang@med.miami.edu

Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact: Carmen Baez-Garcia, RN    305-243-3845    cbaezgarcia@med.miami.edu   
Contact: Barbara Lang, RN    305-243-3845    blang@med.miami.edu   
Principal Investigator: Jeffrey Goldberger, MD         
Sponsors and Collaborators
University of Miami
Investigators
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Principal Investigator: Jeffrey Goldberger, MD University of Miami
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Responsible Party: Jeffrey Goldberger, Professor, University of Miami
ClinicalTrials.gov Identifier: NCT03856632    
Other Study ID Numbers: 20181182
First Posted: February 27, 2019    Key Record Dates
Last Update Posted: June 18, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Additional relevant MeSH terms:
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Atrial Fibrillation
Arrhythmias, Cardiac
Heart Diseases
Cardiovascular Diseases
Pathologic Processes
Liraglutide
Anti-Arrhythmia Agents
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists