Using metformin to treat pulmonary hypertension in heart failure patients

Phase II Trial of Metformin for Pulmonary Hypertension in Heart Failure With Preserved Ejection Fraction

This study is testing if the diabetes drug metformin can help people with heart failure and pulmonary hypertension exercise better and improve their heart function compared to a placebo.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 10 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University of California, San Francisco (Academic / other)
• Locations: 2 sites (San Francisco, California and 1 other locations)
• Trial ID: NCT03629340 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of metformin compared to a placebo in improving exercise capacity and hemodynamics in patients with pulmonary hypertension associated with heart failure with preserved ejection fraction (PH-HFpEF). It is a 12-week blinded crossover trial that will assess various physiological and metabolic responses to the treatment. Participants will undergo detailed phenotyping to gather comprehensive data on their condition and response to metformin.

Who should consider this trial

Good fit: Ideal candidates for this study are adults diagnosed with PH-HFpEF and exhibiting features of metabolic syndrome.

Not a fit: Patients under 18 years old or those with uncontrolled systemic hypertension may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve the quality of life and functional capacity for patients suffering from PH-HFpEF.

How similar studies have performed: While there is limited data on the use of metformin specifically for PH-HFpEF, similar studies exploring metabolic interventions in heart failure have shown promising results.

Eligibility criteria

Inclusion Criteria:

2\. PH-HFpEF Confirmed diagnosis by RHC within the past 6 months:

Mean Pulmonary Arterial Pressure (mPAP) ≥ 25 mm Hg AND Pulmonary artery wedge pressure (PAWP) ≥ 15 mm Hg AND Transpulmonary Gradient (TPG) ≥ 12 mm Hg

OR Exercise measurements

Mean Pulmonary Arterial Pressure (mPAP) ≥ 30 mm Hg AND Pulmonary artery wedge pressure (PAWP) ≥ 20 mm Hg AND PA calculation (change in mPAP/change in cardiac output) = ≥3 mmHg/L/min

3\. Three or more features of metabolic syndrome defined as:

Body Mass Index (BMI) ≥ 30 kg/m² Systolic blood pressure (BP) ≥ 130 mm Hg and/or diastolic BP ≥ 85 mm Hg Elevated waist circumference \> 102 cm in men and \> 88 cm in women Fasting triglyceride (TG) level over 150 mg/dl High-density lipoprotein \<40 mg/dL in men or \< 50 mg/dL in women

Exclusion Criteria:

1. Age less than 18 years;
2. Uncontrolled systemic hypertension based on repeated measurement of sitting systolic blood pressure \>170 mm Hg or sitting diastolic blood pressure \>95 mm Hg at Screening;
3. Systemic sitting blood pressure \< 110 mmHg systolic or \< 60 mm Hg diastolic at Screening;
4. Hemoglobin A1C \> 10;
5. Currently taking metformin or history of intolerance to metformin or contraindication to taking metformin;
6. Known type 1 diabetes
7. Positive urine pregnancy test or breastfeeding
8. Ejection Fraction \< 50%
9. Dementia;

11\. End-stage malignancy; 12. Major cardiovascular event or procedure within 6 weeks prior to enrollment; 13. Severe valvular disease; 14. Other severe acute or chronic medical, psychiatric or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study or would prevent completion of the study; 15. Current Smoker; 16. Hemoglobin \<9 g/dL; 17. Estimated glomerular filtration rate (eGFR) \<30 mL/min/1.73 m2; 18. Receipt of an investigational product or device, or participation in a drug research study within a period of 15 days 19. \<3 months of stable dose of PDE5i

Where this trial is running

San Francisco, California and 1 other locations

• UCSF Medical Center — San Francisco, California, United States (Recruiting)
• University of Pittsburgh Medical Center — Pittsburgh, Pennsylvania, United States (Recruiting)

Study contacts

• Principal investigator: Michael Risbano, MD, MA — University of Pittsburgh
• Study coordinator: Miranda Gilbert, BS, MS

Conditions Pulmonary Hypertension; Heart Failure