Management of Diabetes With Metformin In Patients With Chronic Heart Failure

• Sponsor: University of California, Los Angeles (Other)
• Overall Status: Completed
• CT.gov ID: NCT01122316
• Collaborator: (none)
• Enrollment: 10
• Location: 1
• Arm: 1
• Duration (Months): 28
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The Ahmanson-UCLA Cardiomyopathy Center is conducting a clinical research study that will assess the use of the medication metformin to improve quality of life, exercise capacity, and improved outcomes with patients that have both heart failure and diabetes.

If you participate in this study, you will receive the drug metformin for approximately 3 months. During the study you will undergo comprehensive testing which includes blood draws, an echocardiogram, and an magnetic resonance imaging (MRI)(if you do not have a pacemaker or defibrillator). You will also fill out a questionnaire and keep a blood glucose log.

You must be 18 years old to participate. The study drugs, study follow-up visits, and laboratory tests will be provided free of charge. Participants will be reimbursed up to $200 for their time and travel expenses.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure; Diabetes	Drug: Metformin	N/A

Detailed Description

Heart failure (HF) affects 5 million individuals in the United States including over 10% of elderly persons >75 years. HF mortality is high, with approximately 20% 1-year risk of death (1). Diabetes (DM) is a common co-morbidity in patients with HF, present in approximately 25% of stable outpatients and 40% of hospitalized patients with HF (2). Diabetes in HF patients is associated with higher mortality (3,4). Hyperglycemia is independently associated with hospitalization for HF, longer length of stay during HF hospitalization, as well as higher in-hospital HF mortality (5-7). Furthermore, HF patients with more symptoms and worse functional status are more likely to have insulin resistance (8,9).

Despite the abundance of evidence linking diabetes, insulin resistance, and hyperglycemia to impaired functional status and worse outcomes in patients with HF, there is lack of data and guidelines on optimal strategies to manage diabetes in patients with chronic HF. In retrospective studies, many diabetes medications in HF have been associated with harm including insulin, thiazolidinediones, and sulfonylureas (10). The only anti-hyperglycemic medication that has been associated in retrospective studies with benefit in patients with HF and diabetes is metformin, which recently had its "black box warning" in HF lifted by the FDA, although most physicians are unaware of the change in labeling (10-12). Our analysis of data on 401 advanced, systolic HF patients with DM followed at the Ahmanson-UCLA Cardiomyopathy Center also found metformin therapy to be associated with improvement of left ventricular ejection fraction (LVEF) as well as decreased 1-year mortality (figure 1)(13).

Glycemic control in HF patients has not been prospectively studied; however, improved glycemic control has potential benefits in HF, including improvement of myocardial glucose utilization, decrease of potentially cardiotoxic free fatty acids, and reduced accumulation of myocardial collagen and advanced glycation end-products (14,15). Metformin therapy, compared to insulin and other antidiabetic medications, has potentially beneficial mechanisms of action in HF including insulin sensitization, improvement in lipid profiles, and more efficient myocardial metabolism (16,17). The purpose of this study is to gather pilot data for an anticipated comprehensive study DM management in HF, with the goal of NIH funding.

Study Design

• Study Type: Interventional
• Actual Enrollment: 10 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Management of Diabetes With Metformin In Patients With Chronic Heart Failure
• Study Start Date: Sep 1, 2009
• Actual Primary Completion Date: Jan 1, 2012
• Actual Study Completion Date: Jan 1, 2012

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Metformin	Drug: Metformin; 3. Metformin will be started at 500 mg PO BID and pending lab values may be titrated to 1000 mg PO BID at 1 month.

Outcome Measures

Primary Outcome Measures

1. Health-Related Quality of Life (HRQoL) [3 months]

   HRQoL as assessed by the Minnesota Living With Heart Failure Questionnaire (MLHFQ) The MLHFQ is a self-administered questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on HRQoL, from 0 (none) to 5 (very much). It provides a total score range 0-105. Lower scores indicate better health-related quality of life (HRQoL).

Secondary Outcome Measures

1. Glycated Hemoglobin (HbA1c) [3 months]

   The HbA1c test measures how much glucose is bound to hemoglobin in the red blood cells. The test shows the average level of glucose in blood for the past 3 months (the average lifespan of red blood cells). If glucose levels have been high over recent weeks, the hemoglobin A1c test will be higher.

2. Left Ventricular Ejection Fraction (LVEF) [3 months]

   Obtained from Echocardiography

3. Creatinine Level as a Measure of Renal Function [3 months]

   Serum creatinine

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 90 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Systolic HF of any etiology (left ventricular ejection fraction ≤ 40%)

• Previously-diagnosed, inadequately controlled DM (HbA1c≥7.5%)

• On any combination of anti-diabetic medications excluding metformin

Exclusion Criteria:

• Current metformin therapy

• Previous intolerance to metformin therapy

• Renal dysfunction (creatinine clearance < 60 ml/minute)

• History of lactic acidosis.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Ahmanson-UCLA Cardiomyopathy Center	Los Angeles	California	United States	90095-7368

Sponsors and Collaborators

• University of California, Los Angeles

Investigators

• Principal Investigator: Tamara Horwich, MD, MS, University of California, Los Angeles

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Tamara Horwich, Tamara Horwich, MD, MS, University of California, Los Angeles
• ClinicalTrials.gov Identifier: NCT01122316
• Other Study ID Numbers: 09-06-086-02
• First Posted: May 13, 2010
• Last Update Posted: Sep 4, 2020
• Last Verified: Aug 1, 2020

• Keywords provided by Tamara Horwich, Tamara Horwich, MD, MS, University of California, Los Angeles: Heart Failure; Diabetes; Metformin
• Additional relevant MeSH terms: Heart Failure; Diabetes Mellitus; Metformin

Study Results

Participant Flow

Arm/Group Title	Metformin
Arm/Group Description	Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
Period Title: Overall Study
STARTED	10
COMPLETED	8
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Metformin
Arm/Group Description	Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
Overall Participants	10
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	52.5 (10)
Sex: Female, Male (Count of Participants)
Female	2 20%
Male	8 80%
Race and Ethnicity Not Collected (Count of Participants)

Outcome Measures

1. Primary Outcome

Title	Health-Related Quality of Life (HRQoL)
Description	HRQoL as assessed by the Minnesota Living With Heart Failure Questionnaire (MLHFQ) The MLHFQ is a self-administered questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on HRQoL, from 0 (none) to 5 (very much). It provides a total score range 0-105. Lower scores indicate better health-related quality of life (HRQoL).
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Analysis includes participants who completed intervention and final study assessment

Arm/Group Title	Metformin
Arm/Group Description	Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
Measure Participants	8
Baseline	56 (25)
Three Months	53 (35)

2. Secondary Outcome

Title	Glycated Hemoglobin (HbA1c)
Description	The HbA1c test measures how much glucose is bound to hemoglobin in the red blood cells. The test shows the average level of glucose in blood for the past 3 months (the average lifespan of red blood cells). If glucose levels have been high over recent weeks, the hemoglobin A1c test will be higher.
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Analysis includes participants who completed intervention and final study assessment

Arm/Group Title	Metformin
Arm/Group Description	Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
Measure Participants	8
Baseline	9.1 (2.3)
Three Months	8.9 (3.0)

3. Secondary Outcome

Title	Left Ventricular Ejection Fraction (LVEF)
Description	Obtained from Echocardiography
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Analysis includes participants who completed intervention and final study assessment

Arm/Group Title	Metformin
Arm/Group Description	Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
Measure Participants	8
Baseline	22 (11)
Three Months	28 (11)

4. Secondary Outcome

Title	Creatinine Level as a Measure of Renal Function
Description	Serum creatinine
Time Frame	3 months

Outcome Measure Data

Analysis Population Description

Analysis includes participants who completed intervention and final study assessment

Arm/Group Title	Metformin
Arm/Group Description	Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
Measure Participants	8
Baseline	1.04 (0.18)
Three Months	1.09 (0.2)

Adverse Events

Time Frame	3 months
Arm/Group Title	Metformin
Arm/Group Description	Metformin at 500 mg PO BID and pending lab values may have been titrated to 1000 mg PO BID at 1 month.
All Cause Mortality
	Metformin
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Metformin
	Affected / at Risk (%)	# Events
Total	0/10 (0%)
Other (Not Including Serious) Adverse Events
	Metformin
	Affected / at Risk (%)	# Events
Total	0/10 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.