Metformin as an Adjunctive Therapy to Catheter Ablation in Atrial Fibrillation

This clinical trial is being done to determine if metformin, a drug which is normally used in diabetes, can reduce atrial fibrillation in patients who are having an ablation for atrial fibrillation (AF). Atrial fibrillation is an abnormal heart rhythm which research has shown is related in part to obesity and diabetes.

It is anticipated that the participants treated in the metformin arm will have greater freedom from recurrent atrial arrhythmias after ablation.

Eligible participants enrolled in the trial will be assigned to one of the treatment arms (no treatment or metformin) and have follow-up visits up to approximately 1 year after the ablation. Additionally, all patients will also receive education on lifestyle changes and exercise which are standard of care.

Study Overview

• Status: Recruiting
• Conditions: Atrial Fibrillation
• Intervention / Treatment: Behavioral: Recommendations for lifestyle modification.; Device: AliveCor; Drug: Metformin

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sangeeta Lathkar-Pradham; Phone Number: 734-232-5022; Email: slathkar@umich.edu
• Study Contact Backup: Name: Hakan Oral, MD; Phone Number: 734-763-7141; Email: oralh@umich.edu

Study Locations

• United States
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • University of Michigan
      • Contact: Saneeta Lathkar-Pradham; Phone Number: 734-232-5022; Email: slathkar@umich.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Body Mass Index (BMI) >25 kilograms / square meter (kg/m2) with plan for rhythm control of atrial fibrillation by catheter ablation
• All subjects must be able to understand and willing to sign a written informed consent document.

Exclusion Criteria:

• Individuals who are already taking metformin or other antidiabetic medications, including insulin
• Known diabetes
• Known allergy or Food and Drug Administration (FDA)-labeled contraindication to taking metformin (estimated glomerular filtration rate (eGFR)<30 millilitres per minute (mL/min)/1.73 square meters (m2), hypersensitivity to metformin, acute or chronic metabolic acidosis)
• Patients taking carbonic anhydrase inhibitors
• eGFR below 30 mL/min per 1.73 m2 or other clinical diagnosis of advanced renal disease
• Acute or chronic metabolic acidosis (serum bicarbonate <22 milliequivalents per liter (mEq/L))
• History of significant alcohol use (>2 drinks/day on average)
• History of hepatic dysfunction (serum bilirubin 1.5 times greater than ULN)
• History of New York Heart Association (NYHA) Class III or IV heart failure
• Pregnancy or nursing

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
Experimental: Metformin; Standard of care ablation with recommendations for lifestyle modification and metformin.	Behavioral: Recommendations for lifestyle modification.; All subjects will receive education on lifestyle changes and exercise which are standard of care. This will include discussion with their treating electrophysiologist and a handout.; Device: AliveCor; Device will be used in order to record an electrocardiogram during symptoms perceived to be AF. All patients will be instructed to transmit at least once per week.; Drug: Metformin; Metformin immediate release will be initiated at 250 milligrams (mg) daily (orally), and increased as tolerated to 2000 mg daily over a four week period. If a patient is unable to tolerate a dose increase they will return to their last tolerated dose after omitting one days dosing. 0 to Six weeks after the initiation of drug the patient will undergo (standard of care) ablation with the intent of achieving rhythm control. Participants will stay on the metformin 12 months after the ablation. In addition, all participants will receive education on lifestyle changes and exercise which are standard of care as well as have a discussion with their treating electrophysiologist and receive a handout.; Other Names: Glucophage
Other: Standard of care; Standard of care ablation with recommendations for lifestyle modification.	Behavioral: Recommendations for lifestyle modification.; All subjects will receive education on lifestyle changes and exercise which are standard of care. This will include discussion with their treating electrophysiologist and a handout.; Device: AliveCor; Device will be used in order to record an electrocardiogram during symptoms perceived to be AF. All patients will be instructed to transmit at least once per week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from recurrent atrial arrhythmias by 6 months after a single ablation to eliminate AF	There will be a 3 month blanking period after ablation during which recurrent atrial arrhythmias will not contribute to the primary endpoint.	6 months after ablation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time to recurrence of atrial fibrillation after a 3 month blanking period of ablation		up to 1 year after after ablation
Freedom from recurrent atrial arrhythmias at 1 year after ablation after the blanking period of 3 months		1 year after ablation
Freedom from recurrent atrial arrhythmias at 6 months after repeat ablation		6 months after a repeated ablation
Atrial Fibrillation Severity Score (AFSS)	There are a total of 19 questions (parts A,B, and C) in this questionnaire. This collects information regarding the participants atrial fibrillation. It includes seven questions for subjects to report severity of symptoms (i.e. palpitations, shortness of breath at rest/physical activity, exercise intolerance, fatigue at rest, and lightheadedness/dizziness, chest pain or pressure) on a Likert scale from 0 (subject did not have this symptom) to 5 (symptom bothers subject a great deal).	up to 12 months after ablation
Percent change in weight at 3 months after ablation		3 months after ablation
Percent change in weight at 6 months after ablation		6 months after ablation
Percent change in hemoglobin A1c at 6 months after ablation		6 months after ablation
Percent change in hemoglobin A1C at 12 months after ablation		12 months after ablation
Incidence of major procedural complications	Complications include but are not limited to major bleeding, vascular injury, myocardial perforation, stroke, and mortality.	up to 30 days
Atrial Fibrillation related morbidity during follow-up	During follow-up visits information will be collected regarding Emergency department visits and hospital admissions due to AF, Transient Ischemic Attack (TIA)/cerebrovascular accident (CVA), and mortality. These will be collected as total numbers between groups.	up to approximately 1 year after ablation
Burden of Atrial Fibrillation assessed by AliveCOR Kardia Devices		6 months after ablation
Burden of Atrial Fibrillation assessed by AliveCOR Kardia Devices		1 year after ablation
Burden of Atrial Fibrillation assessed by AliveCOR Kardia Devices		3 months after ablation

Collaborators and Investigators

• Sponsor: University of Michigan
• Investigators: Principal Investigator: Hakan Oral, MD, University of Michigan

Study record dates

Study Major Dates

• Study Start (Actual): January 19, 2021
• Primary Completion (Estimated): August 1, 2024
• Study Completion (Estimated): February 1, 2025

Study Registration Dates

• First Submitted: November 6, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 12, 2020

Study Record Updates

• Last Update Posted (Actual): January 11, 2024
• Last Update Submitted That Met QC Criteria: January 9, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: ablation
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Atrial Fibrillation; Hypoglycemic Agents; Physiological Effects of Drugs; Metformin
• Other Study ID Numbers: HUM00174848

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