Metformin as an Upstream Therapy in Atrial Fibrillation

• Sponsor: The Guthrie Clinic (Other)
• Overall Status: Terminated
• CT.gov ID: NCT02931253
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Actual Duration (Months): 14.9
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to see if the study drug metformin will help patients who are overweight and have atrial fibrillation. This study aims to see if metformin helps patients stay in normal sinus rhythm after a catheter ablation.

Metformin is investigational for use in patients with atrial fibrillation. Metformin is approved by the Food and Drug Administration (FDA) for use in patients with type 2 Diabetes Mellitus. Metformin is used with a proper diet and exercise program to control high blood sugar, and has been shown to help people lose weight. This study aims to look at the effects of metformin on weight loss and heart rhythm in patients with atrial fibrillation.

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation	Drug: Metformin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Metformin as an Upstream Therapy in Atrial Fibrillation
• Actual Study Start Date: Apr 11, 2017
• Actual Primary Completion Date: Jul 10, 2018
• Actual Study Completion Date: Jul 10, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin Group Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks.	Drug: Metformin; Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.
No Intervention: Control Group Standard of care - ablation only

Outcome Measures

Primary Outcome Measures

1. Number of Participants Who Maintain Sinus Rhythm [6 months]

   Number of participants who maintain sinus rhythm, normal heart rhythm by electrocardiogram (ECG)

Secondary Outcome Measures

1. Number of Participants Requiring Hospitalization [6 months]

   Hospitalization related to arrhythmic events or medication side effects

2. Number of Participants Requiring Antiarrhythmic Medications [6 months]

   Total count of participants on anti-arrhythmic medications

3. Number of Participants Requiring Repeat Ablations [6 months]

4. Change in BMI [Baseline to 6 months]

   Average change in BMI from baseline to 6 month.

5. Hemoglobin A1c [Baseline to 6 months]

   Change from baseline to 6 month

6. Number of Participants With Thromboembolic Events [from baseline to 6 months]

   Number of participants who have a thromboembolic event from baseline to 6 months

Other Outcome Measures

1. Weight Loss [baseline to 6 months]

   Weight change from baseline to 6 months.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• All individuals diagnosed with Atrial Fibrillation and choosing to undergo a rhythm control strategy at Robert Packer Hospital with a BMI ≥ 27 will be eligible for the study. 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, have a diagnosis of diabetes, have a known allergy or FDA-labeled contraindication to taking metformin, eGFR below 30 mL/min per 1.73 m2 or other clinical diagnosis of advanced renal disease,, have acute or chronic metabolic acidosis (serum bicarbonate <22 mEq/L), have a history of significant alcohol use (>2 drinks/day on average), have a history of hepatic dysfunction (serum bilirubin 1.5X greater than the upper limit of normal), have a history of New York Heart Association (NYHA) Class III or IV heart failure, or are pregnant will be excluded from the trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Guthrie Clinic	Sayre	Pennsylvania	United States	18840

Sponsors and Collaborators

• The Guthrie Clinic

Investigators

None specified.

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 23, 2018

More Information

Publications

None provided.

• Responsible Party: The Guthrie Clinic
• ClinicalTrials.gov Identifier: NCT02931253
• Other Study ID Numbers: 1602-01
• First Posted: Oct 13, 2016
• Last Update Posted: Jun 11, 2020
• Last Verified: Jun 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Atrial Fibrillation; Metformin

Study Results

Participant Flow

Recruitment Details	Study terminated prior to meeting enrollment target. Enrollment rate slower than expected.

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Period Title: Overall Study
STARTED	2	4
COMPLETED	2	4
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Metformin Group	Control Group	Total
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only	Total of all reporting groups
Overall Participants	2	4	6
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	69 (4)	65 (3)	66 (4)
Sex: Female, Male (Count of Participants)
Female	0 0%	1 25%	1 16.7%
Male	2 100%	3 75%	5 83.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%
Region of Enrollment (participants) [Number]
United States	2 100%	4 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Number of Participants Who Maintain Sinus Rhythm
Description	Number of participants who maintain sinus rhythm, normal heart rhythm by electrocardiogram (ECG)
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Count of Participants [Participants]	1 50%	0 0%

2. Secondary Outcome

Title	Number of Participants Requiring Hospitalization
Description	Hospitalization related to arrhythmic events or medication side effects
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Count of Participants [Participants]	0 0%	0 0%

3. Secondary Outcome

Title	Number of Participants Requiring Antiarrhythmic Medications
Description	Total count of participants on anti-arrhythmic medications
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Count of Participants [Participants]	1 50%	1 25%

4. Secondary Outcome

Title	Number of Participants Requiring Repeat Ablations
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Count of Participants [Participants]	0 0%	0 0%

5. Secondary Outcome

Title	Change in BMI
Description	Average change in BMI from baseline to 6 month.
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Mean (Standard Deviation) [kg/m^2]	1.8 (.8)	1.7 (1.3)

6. Secondary Outcome

Title	Hemoglobin A1c
Description	Change from baseline to 6 month
Time Frame	Baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Mean (Standard Deviation) [percent glycosylated hemoglobin]	.1 (.14)	.15 (.1)

7. Secondary Outcome

Title	Number of Participants With Thromboembolic Events
Description	Number of participants who have a thromboembolic event from baseline to 6 months
Time Frame	from baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Count of Participants [Participants]	0 0%	0 0%

8. Other Pre-specified Outcome

Title	Weight Loss
Description	Weight change from baseline to 6 months.
Time Frame	baseline to 6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Metformin Group	Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.	Standard of care - ablation only
Measure Participants	2	4
Mean (Standard Deviation) [pounds]	2 (6.3)	-.6 (3.4)

Adverse Events

Time Frame	6 month
Arm/Group Title	Metformin Group		Control Group
Arm/Group Description	Metformin 500 mg daily initiated 6 weeks prior to scheduled ablation. Metformin increased to 2000 mg daily (1000 mg twice a day) as tolerated over the initial 3 weeks. Metformin: Metformin will be started as one pill (500 mg metformin) once a day with a meal. If the subject has no side effects from this dose, the dose will be increased to two pills (1000 mg) twice a day to be taken with meals.		Standard of care - ablation only
All Cause Mortality
	Metformin Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)
Serious Adverse Events
	Metformin Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)
Other (Not Including Serious) Adverse Events
	Metformin Group		Control Group
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/4 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.