Cardiometabolic Disease and Pulmonary Hypertension

NCT ID: NCT03349775

Last Updated: 2022-01-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: EARLY_PHASE1
• Total Enrollment: 21 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-27
• Study Completion Date: 2020-12-22

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.

Conditions

Obesity

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: QUADRUPLE

Study Groups

Metformin

Metformin: 500mg twice daily for 1 week, followed by 1g twice daily for a total of 3 months.

Group Type: ACTIVE_COMPARATOR

Metformin

Intervention Type: DRUG

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

Placebo: 500 mgh twice daily for 1 week, followed by 1g twice daily for a total of 3 months.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

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

Intervention Type: DRUG

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 30 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Jennifer En-Sian Ho M.D.

Assistant Physician in Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jennifer E Ho, MD

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

1R01HL134893-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2017P001020

Identifier Type: -

Identifier Source: org_study_id