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

73 Participants Needed

Trial Summary

What is the purpose of this trial?

The primary objective of this study is to determine the impact of two interventions against insulin resistance on the composite endpoint of 10% improvement in baseline six minute walk distance or improvement in World Health Organization (WHO) functional class in humans with pulmonary artery hypertension (PAH).

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.

What data supports the effectiveness of the drug Metformin for Pulmonary Arterial Hypertension?

A pilot study showed that adding Metformin to bosentan therapy in patients with pulmonary arterial hypertension associated with congenital heart defects improved exercise capacity and pulmonary blood flow more than bosentan alone. ^{1 2 3 4 5}

How is the drug Metformin unique for treating pulmonary arterial hypertension?

Metformin is unique for treating pulmonary arterial hypertension because it is traditionally used to manage diabetes by improving insulin sensitivity, and its use in this context is novel, potentially offering a new mechanism of action compared to existing treatments that focus on other pathways. ^{6 7 8 9 10}

Research Team

Anna R Hemnes, MD

Principal Investigator

Vanderbilt University Medical Center

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Influence of Body Weight and Diabetes Mellitus in Patients With Pulmonary Hypertension. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

[Update pulmonary arterial hypertension : Definitions, diagnosis, therapy]. [2018]

3. United States pubmed.ncbi.nlm.nih.gov

Riociguat (adempas): a novel agent for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. [2020]

4. England pubmed.ncbi.nlm.nih.gov

Metformin added to bosentan therapy in patients with pulmonary arterial hypertension associated with congenital heart defects: a pilot study. [2020]

5. United States pubmed.ncbi.nlm.nih.gov

Riociguat for Sarcoidosis-Associated Pulmonary Hypertension: Results of a 1-Year Double-Blind, Placebo-Controlled Trial. [2023]

6. Germany pubmed.ncbi.nlm.nih.gov

The effects and mechanisms of mycophenolate mofetil on pulmonary arterial hypertension in rats. [2021]

7. United States pubmed.ncbi.nlm.nih.gov

The proton pump inhibitor pantoprazole and its interaction with enteric-coated mycophenolate sodium in transplant recipients. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Pharmacokinetic monitoring of mycophenolic acid in heart transplant patients: correlation the side-effects and rejections with pharmacokinetic parameters. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Proton pump inhibitor co-medication reduces mycophenolate acid drug exposure in heart transplant recipients. [2018]

10. England pubmed.ncbi.nlm.nih.gov

Mycophenolate mofetil in organ transplantation: focus on metabolism, safety and tolerability. [2019]