Using metformin to improve heart function in older patients

Metformin for Older Patients With Heart Failure With Preserved Ejection Fraction

This study is testing if the diabetes drug metformin can help older patients with heart failure feel better and improve their overall health.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 60 Years and up
• Sex: All
• Sponsor: Wake Forest University Health Sciences (Academic / other)
• Drugs / interventions: chemotherapy, radiation
• Locations: 2 sites (Charlotte, North Carolina and 1 other locations)
• Trial ID: NCT05093959 on ClinicalTrials.gov

What this trial studies

This trial investigates the effects of metformin on physical function, quality of life, microbiome diversity, leaky gut, and systemic inflammation in older patients with heart failure with preserved ejection fraction (HFpEF). It is a randomized, double-blind, placebo-controlled study involving 80 participants, who will receive either metformin or a placebo for 20 weeks. Participants will start with a low dose of metformin, which will be gradually increased, and will be monitored for adverse events and treatment adherence throughout the study. The trial aims to provide insights into the potential benefits of metformin in this specific patient population.

Who should consider this trial

Good fit: Ideal candidates are older adults aged 60 and above with stable heart failure symptoms and preserved ejection fraction.

Not a fit: Patients with significant ischemic, valvular, pulmonary, or other medical disorders that could account for their symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved physical function and quality of life for older patients suffering from heart failure with preserved ejection fraction.

How similar studies have performed: Other studies have explored the use of metformin in various conditions, but this specific application in older HFpEF patients is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Heart failure with preserved ejection fraction (HFpEF) will be defined in accord with the American College of Cardiology/American Heart Association 2013 guidelines statement on Management of heart failure and as previously described. The 4 key inclusion criteria for HFpEF include: 1) clinical signs and symptoms as scored by National Health and Nutrition Examination Survey (NHANES)-HF Clinical Score ≥3 and the Rich Criteria; 2) a normal left ventricular (LV) ejection fraction (≥50%) by echocardiography; 3) LV diastolic dysfunction \> grade 1 (American Society of Echocardiography Recommendations); 4) no evidence of significant ischemic, valvular, pulmonary or other medical disorder to account for their symptoms.
* Age ≥60
* Stable HF symptoms and medications for ≥3 weeks
* Final eligibility will be based upon all information available at the conclusion of the baseline visits tests, including review of hospital and outpatient records, history, physical examination, echocardiogram, and familiarization/screening exercise test by a board-certified investigator cardiologist who have extensive experience in heart failure investigations in older persons with HFpEF

Exclusion Criteria:

* History of treatment with metformin or other anti-diabetic drug intended to treat diabetes
* Body mass index (BMI) \<25.0
* Uncontrolled dysrhythmia
* Uncontrolled hypertension (systolic blood pressure \[SPB\]\>200 mmHg or diastolic blood pressure \[DBP\]\>100 mmHg at rest)
* Significant anemia (\<9.5 g hemoglobin \[Hb\]) (eligibility will be determined by complete blood count)
* Significant renal insufficiency (estimated glomerular filtration rate \[eGFR\] \<45 ml/min/1.73 m2) (eligibility will be determined by comprehensive metabolic panel)
* Acute or chronic metabolic acidosis
* Type 2 diabetes, or HbA1c\>6.5
* Low vitamin B12 (\<232 pg/mL)
* Known valvular heart disease, infiltrative cardiomyopathy, or hypertrophic obstructive cardiomyopathy with active obstruction as the primary etiology of HF
* Evidence of significant chronic obstructive pulmonary disease (COPD) defined as either: a. On continuous home oxygen therapy for COPD; b. Hospitalization for COPD in last 6 months
* Any condition that in the judgement of the investigator precludes participation in study or study procedures such as significant dementia, mobility impairment, uncontrolled psychiatric disease, etc.
* Alcohol abuse (\>14 drinks/week)
* Current or recent cancer, or chemotherapy/radiation treatment
* Pregnancy-women of child-bearing potential are excluded from participation in this study.
* A treadmill exercise test revealing: a. Evidence of significant ischemia; b. Electrocardiogram: 1mm flat ST depression; c. Stopped exercising due to chest or leg claudication or any reason other than exhaustion/fatigue/dyspnea; d. Exercise SBP \> 240 mmHg, DBP \> 110 mmHg ; e. Unstable hemodynamics or rhythm; f. Unwilling or unable to complete adequate exercise test
* Exclusions for microbiome testing: a. Antibiotics use within last 30 days; b. Diarrhea and/or vomiting within last 30 days; c. Surgery related to gut in last 6 months; d. Inflammatory bowel disease (such as Crohn's disease or ulcerative colitis), or irritable bowel syndrome
* Plans to leave area within 1 year
* Currently participating in other investigational study
* Refuses informed consent

Where this trial is running

Charlotte, North Carolina and 1 other locations

• Atrium Health Sanger Heart and Vascular Clinic Institute — Charlotte, North Carolina, United States (Not_yet_recruiting)
• Wake Forest School of Medicine — Winston-Salem, North Carolina, United States (Recruiting)

Study contacts

• Principal investigator: Dalane W. Kitzman, MD — Wake Forest University Health Sciences
• Study coordinator: Michael B Nelson

Conditions Heart Failure With Preserved Ejection Fraction; heart failure, metformin, inflammation