Metformin for Pulmonary Hypertension HFpEF

NCT03629340 | Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: STUDY19020231R01AG058659
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 2

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.

Conditions

Pulmonary Hypertension; Heart Failure

Outcome Measures

Primary Outcomes (1)

• The primary endpoint of the trial will be mean pulmonary artery pressure (mPAP) during submaximal exercise as compared between placebo and metformin at 12 weeks (i.e. the week 12 RHC of placebo vs week 12 RHC of metformin).

  12 weeks (i.e. the 12th week of placebo vs 12th week of metformin)

Study Arms (2)

Drug: Metformin

EXPERIMENTAL

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

Drug: Metformin

Placebo Oral Capsule

PLACEBO COMPARATOR

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

Drug: Placebo oral capsule

Interventions

Metformin DRUG

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

Drug: Metformin

Placebo oral capsule 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

Placebo Oral Capsule

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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
• \. 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

You may not qualify if:

• Age less than 18 years;
• 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;
• Systemic sitting blood pressure \< 110 mmHg systolic or \< 60 mm Hg diastolic at Screening;
• Hemoglobin A1C \> 10;
• Currently taking metformin or history of intolerance to metformin or contraindication to taking metformin;
• Known type 1 diabetes
• Positive urine pregnancy test or breastfeeding
• Ejection Fraction \< 50%
• Dementia;
• \. 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

Sponsors & Collaborators

• University of California, San Francisco: lead
• National Institute on Aging (NIA): collaborator

Study Sites (2)

UCSF Medical Center

San Francisco, California, 94143, United States

RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

MeSH Terms

Conditions

Hypertension, Pulmonary; Heart Failure

Interventions

Metformin

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases; Heart Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Michael Risbano, MD, MA

  University of Pittsburgh

  PRINCIPAL INVESTIGATOR

• Marc A Simon, MD, MS

  University of California, San Francisco

  STUDY DIRECTOR

Central Study Contacts

Miranda Gilbert, BS, MS

CONTACT

415-514-6351; miranda.gilbert@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 10, 2018
• First Posted: August 14, 2018
• Study Start: February 26, 2019
• Primary Completion: February 1, 2026
• Study Completion: February 1, 2026
• Last Updated: March 10, 2025

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)