Metformin for Pulmonary Hypertension

(PH-HFpEF Trial)

Recruiting at 1 trial location

Overseen By Miranda Gilbert, BS, MS

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: University of California, San Francisco

Must not be taking: Metformin

Disqualifiers: Uncontrolled hypertension, Type 1 diabetes, Dementia, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

10 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether metformin, a common diabetes medication, can benefit individuals with pulmonary hypertension (high blood pressure in the lungs) who also have heart failure with preserved ejection fraction (a type of heart failure where the heart pumps normally but is stiff). Researchers aim to determine if metformin improves participants' functional capacity and affects blood flow in the lungs compared to a placebo (an inactive capsule). Candidates may be suitable if they have recently been diagnosed with pulmonary hypertension and exhibit three or more signs of metabolic syndrome, such as a high body mass index (BMI) or high blood pressure. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Do I need to stop my current medications for this trial?

The trial information does not specify if you need to stop taking your current medications. However, if you are currently taking metformin, you cannot participate in the trial.

Is there any evidence suggesting that metformin is likely to be safe for humans?

Research has shown that metformin is generally safe for people with certain lung conditions. In various studies, patients with lung issues tolerated metformin well. For instance, one study found it safe for those with pulmonary atrial hypertension, a type of high blood pressure in the lungs. This is encouraging because the FDA has already approved metformin for other uses, such as treating diabetes. While it undergoes testing for new applications, it maintains a strong safety record. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for pulmonary hypertension, which often include endothelin receptor antagonists, phosphodiesterase-5 inhibitors, and prostacyclin analogs, Metformin is traditionally used for type 2 diabetes. Researchers are excited about Metformin because it offers a new approach by potentially targeting metabolic pathways involved in pulmonary hypertension. This could mean a novel mechanism of action for managing the condition, which has the potential to complement existing therapies and offer new hope to patients.

What evidence suggests that metformin might be an effective treatment for pulmonary hypertension?

This trial will compare Metformin with a placebo to evaluate its effectiveness for pulmonary hypertension. Research has shown that Metformin might help with high blood pressure in the lungs, especially when related to heart issues. In studies, Metformin lowered blood pressure, improved heart function, and eased the heart's workload. It also helped protect the lungs from further problems. The treatment was safe and well-tolerated by patients with similar health conditions. These findings suggest that Metformin could be effective in treating pulmonary hypertension. ^{1 4 5 6 7}

Who Is on the Research Team?

Michael Risbano, MD, MA

Principal Investigator

University of Pittsburgh

Marc A Simon, MD, MS

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults with PH-HFpEF, a type of heart failure with high blood pressure in the lungs. Participants must have been diagnosed within the last 6 months and show at least three signs of metabolic syndrome. People under 18, those with uncontrolled hypertension or very low blood pressure, severe diabetes, recent major heart events, certain chronic diseases, or who are pregnant/breastfeeding cannot join.

Inclusion Criteria

You have three or more signs of metabolic syndrome as defined.

I was diagnosed with heart failure with preserved ejection fraction by a heart cath test in the last 6 months.

Exclusion Criteria

You are currently smoking cigarettes.

Your hemoglobin A1C level is higher than 10.

You are pregnant or breastfeeding.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive metformin or placebo to assess efficacy on exercise hemodynamics and functional capacity

12 weeks

Regular visits for monitoring and assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin
• Placebo oral capsule

Trial Overview The study aims to see if Metformin can improve how well the heart and lungs work in people with PH-HFpEF compared to a placebo (a pill without any medicine). Patients will be randomly assigned to either receive Metformin or the placebo while their functional capacity and hemodynamics (blood flow) are monitored.

How Is the Trial Designed?

Group I: Drug: Metformin Experimental Treatment 1 Intervention

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

Group II: Placebo Oral Capsule Placebo Group 1 Intervention

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

Metformin is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Glucophage for:

• Type 2 diabetes

Approved in United States as Glucophage for:

• Type 2 diabetes

Approved in Canada as Glucophage for:

• Type 2 diabetes

Approved in Japan as Glucophage for:

• Type 2 diabetes

Approved in China as Glucophage for:

• Type 2 diabetes

Approved in Switzerland as Glucophage for:

• Type 2 diabetes

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

National Institute on Aging (NIA)

Collaborator

Trials

1,841

Recruited

28,150,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7466644/

Metformin in Pulmonary Hypertension in Left Heart Disease Metformin treatment in this model lowered mean arterial pressure, lowered glucose uptake, improved ejection fraction, and decreased left ...

2. ahajournals.org ahajournals.org/doi/10.1161/JAHA.120.018349

Mechanistic Phase II Clinical Trial of Metformin in ... Metformin therapy was safe and well tolerated in patients with PAH in this single‐arm, open‐label phase II study.

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2782337/

Protective role of the antidiabetic drug metformin against ... Metformin protected against PAH, regardless of the initiating stimulus. This protective effect may be related to its anti-remodelling property.

4. clinicaltrials.gov clinicaltrials.gov/study/NCT03617458

NCT03617458 | Interventions Against Insulin Resistance in ... The primary objective of this study is to determine the impact of two interventions against insulin resistance on the composite endpoint of 10% improvement ...

5. thecardiologyadvisor.com thecardiologyadvisor.com/news/metformin-well-tolerated-and-safe-for-the-treatment-of-pulmonary-atrial-hypertension/

Metformin for the Treatment of Pulmonary Atrial Hypertension Metformin was found to be well-tolerated and safe for the treatment of pulmonary atrial hypertension (PAH), according to study results published in the Journal ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/33167773/

Mechanistic Phase II Clinical Trial of Metformin in ... Metformin therapy was safe and well tolerated in patients with PAH in this single-arm, open-label phase II study.

7. clinicaltrials.gov clinicaltrials.gov/study/NCT03349775

Cardiometabolic Disease and Pulmonary Hypertension This study will investigate if metformin can help people with obesity and high pressures inside their lung blood vessels. Metformin is approved by the U.S. Food ...