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Cardiometabolic Disease and Pulmonary Hypertension

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ClinicalTrials.gov Identifier: NCT03349775
Recruitment Status : Recruiting
First Posted : November 22, 2017
Last Update Posted : October 29, 2018
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Jennifer En-Sian Ho M.D., 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.


Condition or disease Intervention/treatment Phase
Obesity Drug: Metformin Drug: Placebo Early Phase 1

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 75 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Cardiometabolic Disease and Pulmonary Hypertension
Actual Study Start Date : November 27, 2017
Estimated Primary Completion Date : September 1, 2022
Estimated Study Completion Date : September 1, 2024

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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




Primary Outcome Measures :
  1. Pulmonary vascular hemodynamics (rest) [ Time Frame: Baseline and 3 months ]
    The metformin and placebo groups will be compared with respect to resting mean pulmonary artery pressure (mmHg)

  2. Pulmonary vascular hemodynamics (exercise) [ Time Frame: 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 :
  1. Effect on pulmonary artery endothelial cell phenotypes [ Time Frame: 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




Information from the National Library of Medicine

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Ages Eligible for Study:   30 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03349775


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

Locations
United States, Massachusetts
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Elizabeth Liu, BS    617-724-3064    ELIU9@MGH.HARVARD.EDU   
Sponsors and Collaborators
Massachusetts General Hospital
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Jennifer E Ho, MD Massachusetts General Hospital

Responsible Party: Jennifer En-Sian Ho M.D., Assistant Physician in Medicine, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT03349775     History of Changes
Other Study ID Numbers: 2017P001020
1R01HL134893-01A1 ( U.S. NIH Grant/Contract )
First Posted: November 22, 2017    Key Record Dates
Last Update Posted: October 29, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Jennifer En-Sian Ho M.D., Massachusetts General Hospital:
Pulmonary Hypertension
BMI
Echocardiography
CPET
6-minute walk test
Cardio Metabolic disease

Additional relevant MeSH terms:
Hypertension
Hypertension, Pulmonary
Vascular Diseases
Cardiovascular Diseases
Lung Diseases
Respiratory Tract Diseases
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs