Cardiometabolic Disease and Pulmonary Hypertension

Early Phase 1

Terminated

• Conditions: Obesity
• Interventions: Drug: Placebo; Drug: Metformin

• Registration Number: NCT03349775
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

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 and Drug Administration (FDA) to treat diabetes, but metformin is not approved by the FDA to treat pulmonary hypertension.

This study will examine whether Metformin will improve the high pressure inside lung blood vessels in people who are obese. The study will help understand the effect of metformin on pressures inside lung blood vessels.

Detailed Description

Obesity can predispose people to develop high pressures inside their lung blood vessels, a condition called pulmonary hypertension, Pulmonary hypertension in turn, can lead to shortness of breath and other health complications such as heart failure. In this study, we seek to identify individuals at risk for the development of high pressures inside lung vessels based on BMI and dyspnea grade 1.

Participants will be screened by echocardiography to estimate pulmonary pressures. Potential participants will undergo invasive cardiopulmonary exercise testing with hemodynamic monitoring, in order to identify individuals with abnormal pulmonary vascular function either at rest or during exercise. Patients who have undergone clinically-indicated cardiopulmonary exercise testing and meet inclusion/exclusion criteria will also be recruited. Those with abnormal pulmonary vascular function will be randomized to receive Metformin or placebo for a total of 3 months under an IND exemption. The primary outcomes include the effect on pulmonary vascular function at rest and during exercise. Secondary outcomes include change in pulmonary artery endothelial cell phenotypes.

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2017-06-06
• Study First Submitted QC: 2017-11-20
• Study First Posted: 2017-11-22
• Study Start: 2017-11-27
• Primary Completion: 2020-12-22
• Study Completion: 2020-12-22
• Status Verified: 2021-12
• Results First Submitted: 2021-12-21
• Results First Submitted QC: 2021-12-21
• Last Update Submitted: 2021-12-21
• Results First Posted: 2022-01-21
• Last Update Posted: 2022-01-21

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 21

Inclusion Criteria

• Age 30-80 years
• History of obesity and current BMI ≥ 25 kg/ m2 for study volunteers or BMI ≥ 25 kg/ m2 for those with clinically indicated CPET or known HFpEF
• History of Dyspnea (Grade 1 or more)
• Able to provide informed consent and willing to comply with study

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Exclusion Criteria

• History of diabetes mellitus
• History of primary pulmonary arterial hypertension
• History of moderate to severe COPD
• History of severe Obstructive Sleep apnea
• History of renal disease (eGFR< 45 mL/min/1.732)
• History of severe liver disease
• History of cardiovascular disease (recent heart attack or stroke) except known HFpEF
• History of blood clot in lung
• History of Splenectomy
• History of Active Cancer
• Platelets count of < 75,000
• International normalized ration (INR) of > 1.5
• History of recent anemia (HB < 9g/dL)
• Current use of Metformin
• Prior LVEF < 50% on echocardiogram
• Indication of severe valvular disease on echo
• Pregnant or planning to become pregnant in next 4 months
• History of HIV infection

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Placebo: 500 mgh twice daily for 1 week, followed by 1g twice daily for a total of 3 months.
Metformin	Metformin	Metformin: 500mg twice daily for 1 week, followed by 1g twice daily for a total of 3 months.

Primary Outcome Measures

Name	Time	Method
Pulmonary Vascular Hemodynamics (Rest)	Baseline and 3 months	The metformin and placebo groups will be compared with respect to resting mean pulmonary artery pressure (mmHg)
Pulmonary Vascular Hemodynamics (Exercise)	Baseline and 3 months	The metformin and placebo groups will be compared with respect to augmentation of mean pulmonary artery pressure divided by augmentation of cardiac output during cardiopulmonary exercise testing (change in mean PAP divided by change in cardiac output from rest to peak exercise)

Secondary Outcome Measures

Name	Time	Method
Effect on Pulmonary Artery Endothelial Cell Phenotypes	baseline and 3 months	We will compare the metformin and placebo groups. Specifically we will examine the following pulmonary artery endothelial cell phenotypes: (1) activation of phospho-eNOS as detected by immunofluorescence staining

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States