Purpose

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.

Condition

Eligibility

Eligible Ages
Between 30 Years and 80 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Age 30-80 years
  • BMI ≥ 30 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

Study Design

Phase
Early Phase 1
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Other
Masking
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Metformin
Metformin: 500mg twice daily for 1 week, followed by 1g twice daily for a total of 3 months.
  • 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 Comparator
Placebo
Placebo: 500 mgh twice daily for 1 week, followed by 1g twice daily for a total of 3 months.
  • 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

Recruiting Locations

Massachusetts General Hospital
Boston, Massachusetts 02114
Contact:
Elizabeth Liu, BS
617-724-3064
ELIU9@MGH.HARVARD.EDU

More Details

NCT ID
NCT03349775
Status
Recruiting
Sponsor
Massachusetts General Hospital

Study Contact

Elizabeth Liu, BS
617-724-3064
ELIU9@MGH.HARVARD.EDU

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.