Metformin + mHealth for Pulmonary Arterial Hypertension

Overseen By Study Coordinator

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must be taking: PAH-specific medications

Disqualifiers: Wheelchair bound, Pregnancy, Type I diabetes, Cirrhosis, others

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

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores the effectiveness of metformin, a medication commonly used for diabetes, in individuals with pulmonary arterial hypertension (PAH). Researchers aim to determine if metformin, combined with a mobile health (mHealth) platform that sends supportive text messages, can enhance physical activity and overall health in participants. The trial includes four groups: some will receive metformin with mHealth support, others will receive a placebo with mHealth or usual care, and one group will receive metformin with usual care. Suitable candidates for this trial have PAH, maintain a stable medication regimen, can move without aids like canes, and own a smartphone with texting capabilities. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that your PAH-specific medication regimen be stable for three months before joining, so you should not stop taking those medications. However, if you have had only one diuretic adjustment in the past three months, you can still participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that metformin is generally safe and well-tolerated for people with pulmonary arterial hypertension (PAH). In one study, participants took metformin without major issues, indicating its effectiveness for this condition. Another study found some side effects, but they were not serious. The FDA has also approved metformin for treating diabetes, which supports its safety.

For the mHealth intervention, studies indicate it is safe and can improve the quality of life for people with PAH. This intervention uses technology to send supportive messages, encouraging individuals to stay active and healthy.

Overall, previous research suggests these treatments are safe for humans, with metformin having a well-established safety record. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Metformin + mHealth treatment for Pulmonary Arterial Hypertension (PAH) because it combines a well-known diabetes medication, metformin, with an innovative digital health component. Metformin's potential to improve blood vessel function offers a new angle compared to standard treatments like endothelin receptor antagonists and phosphodiesterase-5 inhibitors, which primarily focus on dilating blood vessels or reducing blood pressure. The mHealth platform adds a unique twist by encouraging patients to stay active and engaged through motivational text messages, which can enhance the effectiveness of the treatment and promote a healthier lifestyle. This combination of medication and technology might offer a more holistic approach to managing PAH, potentially improving both physical and mental well-being.

What evidence suggests that this trial's treatments could be effective for pulmonary arterial hypertension?

Research shows that metformin might help people with pulmonary arterial hypertension (PAH). Previous studies found that metformin is safe and well-tolerated for these patients. It may help by lowering blood pressure and improving heart function in related conditions. Additionally, metformin reduced the growth of certain cells in PAH model rats, which could help manage the disease. In this trial, some participants will receive metformin combined with an mHealth intervention, while others will receive metformin with usual care. These findings suggest that metformin might improve physical endurance and overall heart health in people with PAH. ^{6 7 8 9 10}

Who Is on the Research Team?

Anna R Hemnes, MD

Principal Investigator

Vanderbilt University Medical Center

Are You a Good Fit for This Trial?

This trial is for adults over 18 with pulmonary arterial hypertension (PAH) who are able to walk and have been on a stable PAH medication regimen. They must own a smartphone with Bluetooth and data plan. Excluded are those with severe liver disease, untreated thyroid issues, certain physical limitations, pregnancy, poor kidney function, specific lung function criteria or type I diabetes.

Inclusion Criteria

Subjects must own a Bluetooth capable modern smartphone capable of receiving and sending text messages and an active data plan

My PAH medication has been the same for the last 3 months, except for one diuretic change.

I have been diagnosed with PAH due to unknown causes, genetics, or exposure to drugs/toxins.

Exclusion Criteria

Pregnancy

My lung function is good and my chest scans are normal.

I have Type I diabetes.

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 and engage in mHealth intervention or usual care for 12 weeks

12 weeks

Regular monitoring through mHealth platform and routine visits

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Metformin
• mHealth Intervention
• Placebo
• Usual Care

Trial Overview

The study tests if Metformin or an mHealth intervention can improve walking distance by 10% or WHO functional class in PAH patients compared to placebo/usual care. Participants will be randomly assigned to one of the interventions.

How Is the Trial Designed?

Group I: Metformin + mHealth Intervention Active Control 2 Interventions

Patients will receive active ingredient medicine with mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po twice a day (BID) x 5 days, 500mg by mouth (po) three times a day (TID) x 5 days,1000mg po BID x 69 days (12 weeks total).

Group II: Metformin + Usual Care Active Control 2 Interventions

Patient will receive active ingredient medicine with routine medical care. Subjects will receive metformin 500mg. Patients will titrate the medication as follows: 500mg po daily x 5 days, 500mg po BID x 5 days, 500mg po TID x 5 days,1000mg po BID x 69 days (12 weeks total).

Group III: Placebo + mHealth Intervention Placebo Group 2 Interventions

Patient will receive non active medicine and the mHealth texting platform, which are messages designed to facilitate self-awareness, reinforce step targets, and link physical activity with a reward or memorable cue.

Group IV: Placebo + Usual Care Placebo Group 2 Interventions

Patient will receive non active medicine and routine medical care.

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?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

The Cleveland Clinic

Collaborator

Trials

1,072

Recruited

1,377,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

Published Research Related to This Trial

Riociguat (Adempas) is an innovative medication specifically designed to treat pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH), conditions that cause high blood pressure in the lungs.

Clinical studies have demonstrated that riociguat effectively improves exercise capacity and overall functional status in patients with these types of pulmonary hypertension, making it a valuable treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Khaybullina, D., Patel, A., Zerilli, T.[2020]

In a double-blind placebo-controlled trial involving 16 patients with sarcoidosis-associated pulmonary hypertension, riociguat significantly delayed clinical worsening compared to placebo, with no patients on riociguat meeting the worsening criteria versus five on placebo.

Riociguat also improved exercise capacity, as shown by a median increase of 42.7 meters in the 6-minute walk distance (6MWD) compared to a decrease of 55.9 meters in the placebo group, indicating its efficacy without significant adverse events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Riociguat for Sarcoidosis-Associated Pulmonary Hypertension: Results of a 1-Year Double-Blind, Placebo-Controlled Trial. Baughman, RP., Shlobin, OA., Gupta, R., et al.[2023]

Citations

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pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC7763730/

Mechanistic Phase II Clinical Trial of Metformin in ...

In this pilot trial, we found that metformin is safe in patients with pulmonary arterial hypertension and that, in secondary analyses, metformin ...

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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 ...

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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 ...

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withpower.com

withpower.com/trial/phase-3-insulin-resistance-7-2018-a6c0b

Metformin + mHealth for Pulmonary Arterial Hypertension

The primary objective of this study is to determine the impact of two interventions against insulin resistance on the composite endpoint of 10% improvement ...

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frontiersin.org

frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1577570/full

Pulmonary artery-targeted low-dose metformin-loaded ...

Results: We successfully prepared MET nanocapsules and demonstrated their effectiveness in inhibiting PASMC proliferation. In PAH model rats, MET nanocapsule ...

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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. Exploratory analyses suggest ...

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pubmed.ncbi.nlm.nih.gov

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

Mechanistic Phase II Clinical Trial of Metformin in ...

Conclusions Metformin therapy was safe and well tolerated in patients with PAH in this single-arm, open-label phase II study. Exploratory ...

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ahajournals.org

ahajournals.org/doi/10.1161/circ.150.suppl_1.4118959

Abstract 4118959: Pulmonary Artery-Targeted Metformin- ...

Metformin can be able to treat PAH but is associated with significant side effects. This study aims to enhance the efficacy and safety of ...

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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 ...

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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.