Metformin for Pulmonary Hypertension HFpEF

NCT ID: NCT03629340

Last Updated: 2025-03-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-02-26
• Study Completion Date: 2026-02-28

Brief Summary

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.

Detailed 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.

Conditions

Pulmonary Hypertension; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Drug: Metformin

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

Group Type: EXPERIMENTAL

Metformin

Intervention Type: DRUG

500 mg PO BID x 1 week then increase to 1000 mg PO BID x 11 weeks

Placebo Oral Capsule

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

Group Type: PLACEBO_COMPARATOR

Placebo oral capsule

Intervention Type: DRUG

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

Interventions

Metformin

500 mg PO BID x 1 week then increase to 1000 mg PO BID x 11 weeks

Intervention Type: DRUG

Placebo oral capsule

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

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute on Aging (NIA)

NIH

Sponsor Role: collaborator

University of California, San Francisco

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael Risbano, MD, MA

Role: PRINCIPAL_INVESTIGATOR

University of Pittsburgh

Marc A Simon, MD, MS

Role: STUDY_DIRECTOR

University of California, San Francisco

Locations

UCSF Medical Center

San Francisco, California, United States

Site Status: RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Miranda Gilbert, BS, MS

Role: CONTACT

miranda.gilbert@ucsf.edu

415-514-6351

Facility Contacts

Miranda Gilbert

Role: primary

miranda.gilbert@ucsf.edu

415-514-6351

Sara Onesi, RN

Role: primary

onesisa@upmc.edu

412-864-3265

Other Identifiers

R01AG058659

Identifier Type: NIH

Identifier Source: secondary_id

View Link

STUDY19020231

Identifier Type: -

Identifier Source: org_study_id