Metformin for Pulmonary Hypertension HFpEF (PH-HFpEF)

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

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.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Pulmonary Hypertension
• Intervention / Treatment: Drug: Metformin; Drug: Placebo oral capsule

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.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Miranda Gilbert, BS, MS; Phone Number: 415-514-6351; Email: miranda.gilbert@ucsf.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • Recruiting
      • UCSF Medical Center
      • Principal Investigator: Marc A Simon, MD, MS
      • Contact: Miranda Gilbert; Phone Number: 415-514-6351; Email: miranda.gilbert@ucsf.edu
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Recruiting
      • University of Pittsburgh Medical Center
      • Contact: Sara Onesi, RN; Phone Number: 412-864-3265; Email: onesisa@upmc.edu
      • Principal Investigator: Michael Risbano, MD, MA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Drug: Metformin; 500mg PO (by mouth) BID (two times daily) x 1 week then increase to 1000mg PO BID x 11 weeks	Drug: Metformin; 500 mg PO BID x 1 week then increase to 1000 mg PO BID x 11 weeks
Placebo Comparator: 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	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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)

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Institute on Aging (NIA)
• Investigators: Study Director: Marc A Simon, MD, MS, University of California, San Francisco; Principal Investigator: Michael Risbano, MD, MA, University of Pittsburgh

Study record dates

Study Major Dates

• Study Start (Actual): February 26, 2019
• Primary Completion (Estimated): February 1, 2026
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: August 10, 2018
• First Submitted That Met QC Criteria: August 10, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 7, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Heart Diseases; Respiratory Tract Diseases; Lung Diseases; Heart Failure; Hypertension; Hypertension, Pulmonary; Physiological Effects of Drugs; Hypoglycemic Agents; Metformin
• Other Study ID Numbers: STUDY19020231; R01AG058659 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes