Evidence map›Paper›PMID 33167773›Full record

Trial reportJournal of the American Heart Association2020

Mechanistic Phase II Clinical Trial of Metformin in Pulmonary Arterial Hypertension.

Evan L Brittain, Kevin Niswender, Vineet Agrawal, Xinping Chen, Run Fan, Meredith E Pugh, Todd W Rice, Ivan M Robbins, Haocan Song, Christopher Thompson and 6 more

2 registry-linked trialsOpen access · goldAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Journal of the American Heart Association, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 55 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
55citing papers in PubMed, 1 pooled it
5.8field-weighted citation impact, top 3% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

NCT05853601 phase1 / phase2active not recruitingnot on this mapstarted 2023, after this paper: background citation

Theophylline Prophylaxis During Hypothermia to Limit Neonatal Nephron Damage

TypeinterventionalSponsorMedical College of WisconsinRan2023 to 2027Enrolled30ConditionsAcute Kidney Injury, HIEArmsSingle Dose Theophylline, Repeat Dose Theophylline
NCT07120971 early_phase1recruitingnot on this mapstarted 2025, after this paper: background citation

A Phase 0/Phase 1 Trial of Metformin for Premature Infants With Bronchopulmonary Dysplasia

TypeinterventionalSponsorMedical College of WisconsinRan2025 to 2030Enrolled40ConditionsBronchopulmonary Dysplasia (BPD)ArmsMetformin (open-label)
3 · Its place in the literature

Who cites it

55 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

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  10. Proteomic and metabolomic profiling nominates druggable targets and biomarkers for pulmonary arterial hypertension-associated myopathy and exercise intolerance in male monocrotaline rats.The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors at 1 institution in 1 country.

Evan L BrittainDivision of Cardiovascular Medicine Vanderbilt University Medical Center Nashville TN.
Kevin NiswenderDivision of Diabetes, Endocrinology, and Metabolism Vanderbilt University Medical Center Nashville TN.
Vineet AgrawalDivision of Cardiovascular Medicine Vanderbilt University Medical Center Nashville TN.
Xinping ChenDivision of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN.
Run FanDepartment of Biostatistics Vanderbilt University Medical Center Nashville TN.
Meredith E PughDivision of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN.
Todd W RiceDivision of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN.
Ivan M RobbinsDivision of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN.
Haocan SongDepartment of Biostatistics Vanderbilt University Medical Center Nashville TN.
Christopher ThompsonVanderbilt University Institute of Imaging ScienceVanderbilt University Medical Center Nashville TN.
Fei YeDepartment of Biostatistics Vanderbilt University Medical Center Nashville TN.
Chang YuDepartment of Biostatistics Vanderbilt University Medical Center Nashville TN.
He ZhuVanderbilt University Institute of Imaging ScienceVanderbilt University Medical Center Nashville TN.
James WestDivision of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN.
John H NewmanDivision of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN.
Anna R HemnesDivision of Allergy, Pulmonary and Critical Care Medicine Vanderbilt University Medical Center Nashville TN.
Vanderbilt University Medical Center · US

Funding

Vanderbilt Institute for Clinical and Translational Research (VICTR) -Identifying correlates of functional immunity in SARS-CoV-2 convalescent plasmaUL1TR002243 · NCATS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI Paul A. Harris, Wesley H Self · 2017 to 2026
$130.7M
Sex Hormones in Pulmonary Arterial HypertensionP01HL108800 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI NEWMAN, JOHN HUGHES · 2012 to 2021
$22.0M
Interventions Against the Molecular Etiology of BMPR2-induced PAHR01HL095797 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI WEST, JAMES D · 2010 to 2022
$6.7M
Lipid Deposition in the Right Ventricle in Pulmonary Arterial HypertensionR01HL122417 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI HEMNES, ANNA R · 2015 to 2019
$2.7M
NCATS NIH HHS UL1 TR002243NHLBI NIH HHS P01 HL108800NHLBI NIH HHS R01 HL095797NHLBI NIH HHS R01 HL122417
6 · The paper itself

Abstract

Background Metabolic dysfunction is highly prevalent in pulmonary arterial hypertension (PAH) and likely contributes to both pulmonary vascular disease and right ventricular (RV) failure in part because of increased oxidant stress. Currently, there is no cure for PAH and human studies of metabolic interventions, generally well tolerated in other diseases, are limited in PAH. Metformin is a commonly used oral antidiabetic that decreases gluconeogenesis, increases fatty acid oxidation, and reduces oxidant stress and thus may be relevant to PAH. Methods and Results We performed a single-center, open-label 8-week phase II trial of up to 2 g/day of metformin in patients with idiopathic or heritable PAH with the co-primary end points of safety, including development of lactic acidosis and study withdrawal, and plasma oxidant stress markers. Exploratory end points included RV function via echocardiography, plasma metabolomic analysis performed before and after metformin therapy, and RV triglyceride content by magnetic resonance spectroscopy in a subset of 9 patients. We enrolled 20 patients; 19/20 reached the target dose and all completed the study protocol. There was no clinically significant lactic acidosis or change in oxidant stress markers. Metformin did not change 6-minute walk distance but did significantly improve RV fractional area change (23±8% to 26±6%,

Indexed as

AdultCohort StudiesFemaleHumansHypoglycemic AgentsLipidsMaleMetforminMiddle AgedOxidative StressPulmonary Arterial HypertensionTriglyceridesVentricular Dysfunction, RightHypoglycemic AgentsLipidsMetforminTriglyceridesinsulin resistancemetforminpulmonary arterial hypertensionright ventricle

Identifiers

PMID33167773
PMCPMC7763730
OpenAlexW3100556329

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.