Metformin for Pulmonary Hypertension HFpEF (PH-HFpEF)

University of California San Francisco (UCSF)

Status and phase: Enrolling; Phase 2

Conditions: Heart Failure; Pulmonary Hypertension

Treatments: Drug: Metformin; Drug: Placebo oral capsule

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03629340

R01AG058659 (U.S. NIH Grant/Contract)

STUDY19020231

Details and patient eligibility

About

The main objective of this study is to determine the clinical efficacy of metformin versus placebo and the therapeutic response with regards to functional capacity and hemodynamics in PH-HFpEF.

Full description

This is a 12-week blinded cross over trial of metformin in PH-HFpEF to improve exercise hemodynamics, functional capacity, and glucose metabolism. This phase II clinical trial will provide detailed phenotyping, physiological and mechanistic data on PH-HFpEF.

Enrollment: 10 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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;

10. 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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10 participants in 2 patient groups, including a placebo group

Drug: Metformin

Experimental group

Description:

500mg PO (by mouth) BID (two times daily) x 1 week then increase to 1000mg PO BID x 11 weeks

Treatment:

Drug: Metformin

Placebo Oral Capsule

Placebo Comparator group

Description:

Placebo capsule that is of identical size, shape, and color to experimental drug capsule PO (by mouth) BID (two times each day) for 12 weeks

Treatment:

Drug: Placebo oral capsule