Cardiometabolic Disease and Pulmonary Hypertension

Obesity Clinical Trial

Official title:

Cardiometabolic Disease and Pulmonary Hypertension

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03349775
• Other study ID #: 2017P001020
• Secondary ID: 1R01HL134893-01A
• Status: Terminated
• Phase: Early Phase 1
• Start date: November 27, 2017
• Est. completion date: December 22, 2020

Study information

• Verified date: December 2021
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 21
• Est. completion date: December 22, 2020
• Est. primary completion date: December 22, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 80 Years

Eligibility

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

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

Related Conditions & MeSH terms

• Hypertension
• Hypertension, Pulmonary
• Obesity

Intervention

Drug:
• Metformin
One capsule by mouth twice a day, followed by an increase to two capsules by mouth twice a day for a total of 3 months
• Placebo
One capsule by mouth twice a day, followed by an increase to two capsules by mouth twice a day for a total of 3 months

Locations

Country	Name	City	State
United States	Massachusetts General Hospital	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Pulmonary Vascular Hemodynamics (Rest)	The metformin and placebo groups will be compared with respect to resting mean pulmonary artery pressure (mmHg)	Baseline and 3 months
Primary	Pulmonary Vascular Hemodynamics (Exercise)	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)	Baseline and 3 months
Secondary	Effect on Pulmonary Artery Endothelial Cell Phenotypes	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	baseline and 3 months