Cardiometabolic Disease and Pulmonary Hypertension

NCT03349775 | Terminated Early Phase 1 Results DMC FDA Drug

• 2 other identifiers: 2017P0010201R01HL134893-01A1
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Obesity

Keywords

Pulmonary Hypertension; BMI; Echocardiography; CPET; 6-minute walk test; Cardio Metabolic disease

Outcome Measures

Primary Outcomes (2)

• 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

• 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 Outcomes (1)

• Effect on Pulmonary Artery Endothelial Cell Phenotypes

  baseline and 3 months

Study Arms (2)

Metformin

ACTIVE COMPARATOR

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

Drug: Metformin

Placebo

PLACEBO COMPARATOR

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

Drug: Placebo

Interventions

Metformin 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

Metformin

Placebo 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

Eligibility Criteria

• Age: 30 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Obesity; Hypertension, Pulmonary

Interventions

Metformin

Condition Hierarchy (Ancestors)

Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Limitations and Caveats

After discussion with the Data Safety Monitoring Board and NIH, the randomized clinical trial involving metformin vs. placebo was terminated due to slow enrollment in the setting of the COVID-19 pandemic, resulting in small numbers of subjects analyzed.

Results Point of Contact

• Title: Dr. Jennifer Ho
• Organization: Beth Israel Deaconness Medical Center

jho@bidmc.harvard.edu

617-735-4102

Study Officials

• Jennifer E Ho, MD

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Physician in Medicine

Study Record Dates

• First Submitted: June 6, 2017
• First Posted: November 22, 2017
• Study Start: November 27, 2017
• Primary Completion: December 22, 2020
• Study Completion: December 22, 2020
• Last Updated: January 21, 2022
• Results First Posted: January 21, 2022

Record last verified: 2021-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)