Evidence map›Paper›PMID 24808022›Full record

ArticleNeurology2014

PDE5 inhibition alleviates functional muscle ischemia in boys with Duchenne muscular dystrophy.

Michael D Nelson, Florian Rader, Xiu Tang, Jane Tavyev, Stanley F Nelson, M Carrie Miceli, Robert M Elashoff, H Lee Sweeney, Ronald G Victor

Registry-linked trialOpen access · bronzeAbstract readControlled Clinical Trial
PubMed Full text at PMC Publisher
In one paragraph

Article in Neurology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06290713 (Vasodilators and Exercise as Adjuvant Therapy for Duchenne Muscular Dystrophy), which is not on this map. Cited by 57 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
57citing papers in PubMed, 2 pooled it
43.0field-weighted citation impact, top 1% 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.

NCT06290713 phase2recruitingnot on this mapstarted 2024, after this paper: background citation

Vasodilators and Exercise as Adjuvant Therapy for Duchenne Muscular Dystrophy (VASO-REx Study)

TypeinterventionalSponsorUniversity of FloridaRan2024 to 2026Enrolled50ConditionsDuchenne Muscular Dystrophy, Duchenne Disease, Muscular Dystrophy, Muscular Dystrophy in ChildrenArmsTadalafil, Placebo, Exercise Training
3 · Its place in the literature

Who cites it

57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 105 citations in OpenAlex.

  1. Pooled it
  2. Guideline
  3. Trial
  4. Trial
  5. Trial
  6. Effects of Sildenafil on Cerebrovascular Reactivity in Patients with Becker Muscular Dystrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017
    Trial
  7. Trial
  8. Article
  9. HHandbook of experimental pharmacology · 2026
    Review
  10. Review
  11. Article
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Review
  18. Article
  19. Article
  20. Article
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

9 authors at 1 institution in 1 country.

Michael D NelsonFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
Florian RaderFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
Xiu TangFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
Jane TavyevFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
Stanley F NelsonFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
M Carrie MiceliFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
Robert M ElashoffFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
H Lee SweeneyFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia.
Ronald G VictorFrom The Heart Institute (M.D.N., F.R., X.T., R.G.V.), and Department of Pediatrics (J.T.), Cedars-Sinai Medical Center, Los Angeles; Departments of Human Genetics (S.F.N.) and Pathology and Laboratory Medicine (S.F.N.), David Geffen School of Medicine at UCLA, Los Angeles; Department of Microbiology Immunology and Molecular Genetics (M.C.M.), David Geffen School of Medicine and College of Letters and Sciences, UCLA, Los Angeles; Department of Biomathematics (R.M.E.), and Department of Biostatistics, School of Public Health (R.M.E.), University of California, Los Angeles; and Pennsylvania Muscle Institute (H.L.S.), Department of Medicine, University of Pennsylvania, Philadelphia. Ronald.Victor@cshs.org.
University of California, Los Angeles · US

Funding

Women's CancersP30CA016042 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Samuel Wheeler French · 1985 to 2026
$134.5M
SURGICAL ONCOLOGY WITH COMBINATION THERMO-CHEMOTHERAPYP01CA029605 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI COCHRAN, ALISTAIR JOHN · 1985 to 2013
$75.2M
UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Training and education CoreU54AR052646 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI MCNALLY, ELIZABETH M, SWEENEY, H LEE · 2005 to 2020
$24.1M
Pharmacology CoreU54NS058572 · NINDS · UNIVERSITY OF PENNSYLVANIA · PI SWEENEY, H LEE · 2007 to 2011
$15.1M
Pathology and Molecular Imaging CoreP01HL110869 · NHLBI · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI MILEWICZ, DIANNA M · 2012 to 2016
$10.4M
MOCSLID-DCCR01HL089901 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ELASHOFF, ROBERT M · 2008 to 2012
$9.1M
UCLA Muscular Dystrophy Core CenterP30AR057230 · NIAMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SPENCER, MELISSA JAN · 2009 to 2018
$6.2M
Structure and Function of Myosin VIR01DC009100 · NIDCD · UNIVERSITY OF PENNSYLVANIA · PI SWEENEY, H LEE · 2007 to 2022
$6.0M
Rapid Phenotyping for Rare Variant Discovery in AutismR01NS073871 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI NELSON, STANLEY F. · 2011 to 2015
$3.1M
Planning a Multicenter Trial of PDE5A Inhibition for Duchenne Muscular DystrophyU34AR062893 · NIAMS · CEDARS-SINAI MEDICAL CENTER · PI VICTOR, RONALD G · 2012 to 2012
$443k
Cellular models of microvillus inclusion diseaseR21DK096463 · NIDDK · UNIVERSITY OF PENNSYLVANIA · PI SWEENEY, H LEE · 2012 to 2013
$432k
NCATS NIH HHS UL1 TR000124NCATS NIH HHS UL1TR000124NCI NIH HHS P01 CA029605NCI NIH HHS P30 CA016042NCI NIH HHS P30CA016042NHLBI NIH HHS P01 HL110869NHLBI NIH HHS R01 HL089901NIAMS NIH HHS P30 AR057230NIAMS NIH HHS U34AR062893NIAMS NIH HHS U54 AR052646NIDCD NIH HHS R01 DC009100NIDDK NIH HHS R21 DK096463NINDS NIH HHS R01 NS073871NINDS NIH HHS U54 NS058572
6 · The paper itself

Abstract

objectiveTo determine whether phosphodiesterase type 5 (PDE5) inhibition can alleviate exercise-induced skeletal muscle ischemia in boys with Duchenne muscular dystrophy (DMD).

methodsIn 10 boys with DMD and 10 healthy age-matched male controls, we assessed exercise-induced attenuation of reflex sympathetic vasoconstriction, i.e., functional sympatholysis, a protective mechanism that matches oxygen delivery to metabolic demand. Reflex vasoconstriction was induced by simulated orthostatic stress, measured as the decrease in forearm muscle oxygenation with near-infrared spectroscopy, and performed when the forearm muscles were rested or lightly exercised with rhythmic handgrip exercise. Then, the patients underwent an open-label, dose-escalation, crossover trial with single oral doses of tadalafil or sildenafil.

resultsThe major new findings are 2-fold: first, sympatholysis is impaired in boys with DMD-producing functional muscle ischemia-despite contemporary background therapy with corticosteroids alone or in combination with cardioprotective medication. Second, PDE5 inhibition with standard clinical doses of either tadalafil or sildenafil alleviates this ischemia in a dose-dependent manner. Furthermore, PDE5 inhibition also normalizes the exercise-induced increase in skeletal muscle blood flow (measured by Doppler ultrasound), which is markedly blunted in boys with DMD.

conclusionsThese data provide in-human proof of concept for PDE5 inhibition as a putative new therapeutic strategy for DMD. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that in patients with DMD, PDE5 inhibition restores functional sympatholysis.

Indexed as

Muscle, SkeletalAdolescentCarbolinesChildExerciseForearmHumansIschemiaMaleMuscular Dystrophy, DuchennePhosphodiesterase 5 InhibitorsPiperazinesPurinesSildenafil CitrateSpectroscopy, Near-InfraredSulfonesCarbolinesPhosphodiesterase 5 InhibitorsPiperazinesPurinesSildenafil CitrateSulfonesTadalafil

Identifiers

PMID24808022
PMCPMC4118495
OpenAlexW2161203480

What OpenQuestion holds

Textmetadata
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.