Clinical trial NCT03349775: Cardiometabolic Disease and Pulmonary Hypertension
Official title: Cardiometabolic Disease and Pulmonary Hypertension
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: EARLY_PHASE1
Conditions: Obesity
Keywords: Pulmonary Hypertension
BMI
Echocardiography
CPET
6-minute walk test
Cardio Metabolic disease
Lead sponsor: Massachusetts General Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-11-22
Enrollment: 21
Sex: ALL
Minimum age (years): 30
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Pulmonary Vascular Hemodynamics (Rest)
timeFrame: Baseline and 3 months
measure: Pulmonary Vascular Hemodynamics (Exercise)
timeFrame: Baseline and 3 months
Secondary outcomes:
measure: Effect on Pulmonary Artery Endothelial Cell Phenotypes
timeFrame: baseline and 3 months
Other outcomes:
Locations:
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
Study officials:
affiliation: Massachusetts General Hospital
name: Jennifer E Ho, MD
role: PRINCIPAL_INVESTIGATOR
References: