Evidence map›Paper›PMID 34264994›Full record

Trial reportPloS one2021

In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial.

Baback Roshanravan, Sophia Z Liu, Amir S Ali, Eric G Shankland, Chessa Goss, John K Amory, H Thomas Robertson, David J Marcinek, Kevin E Conley

Open access · goldAbstract readRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
2.3field-weighted citation impact, top 11% 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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 35 citations in OpenAlex.

  1. Trial
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  9. Contemporary insights into elamipretide's mitochondrial mechanism of action and therapeutic effects.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2025
    Review
  10. Review
  11. Review
  12. What can ATP content tell us about Barth syndrome muscle phenotypes?Journal of translational genetics and genomics · 2025
    Article
  13. Article
  14. Review
  15. Article
  16. Article
  17. Mitochondrial Targeted Interventions for Aging.Cold Spring Harbor perspectives in medicine · 2024
    Review
  18. Review
  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 2 institutions in 1 country.

Baback RoshanravanDepartment of Medicine, Division of Nephrology, University of California Davis, Sacramento, California, United States of America.
Sophia Z LiuDepartment of Radiology, University of Washington, Seattle, Washington, United States of America.
Amir S AliDepartment of Radiology, University of Washington, Seattle, Washington, United States of America.
Eric G ShanklandDepartment of Radiology, University of Washington, Seattle, Washington, United States of America.
Chessa GossInstitute of Translational Health Sciences, University of Washington, Seattle, Washington, United States of America.
John K AmoryDepartment of Medicine, University of Washington, Seattle, Washington, United States of America.
H Thomas RobertsonDepartment of Medicine, University of Washington, Seattle, Washington, United States of America.
David J MarcinekDepartment of Radiology, University of Washington, Seattle, Washington, United States of America.ORCID 0000-0001-5187-2149
Kevin E ConleyDepartment of Radiology, University of Washington, Seattle, Washington, United States of America.
University of Washington · USUniversity of California, Davis · US

Funding

Institute of Translational Health SciencesUL1TR000423 · NCATS · UNIVERSITY OF WASHINGTON · PI DISIS, MARY L. · 2012 to 2016
$49.4M
SPECIFICITY OF OXYGEN DNA DAMAGE AND MUTAGENESISP01AG001751 · NIA · UNIVERSITY OF WASHINGTON · PI MACCOSS, MICHAEL · 1985 to 2021
$29.6M
Skeletal muscle dysfunction in persons with chronic kidney diseaseK23DK099442 · NIDDK · UNIVERSITY OF WASHINGTON · PI ROSHANRAVAN, BABACK · 2013 to 2017
$777k
MR Console UpgradeS10OD016201 · OD · UNIVERSITY OF WASHINGTON · PI CONLEY, KEVIN E · 2013 to 2013
$575k
MULTIDIRECTIONAL POSTURAL CONTROLF32AG005738 · NIA · EMANUEL HOSPITAL AND HEALTH CENTER · PI HENRY, SHARON M · 1996 to 1996
–
NCATS NIH HHS UL1 TR000423NIA NIH HHS F32 AG005738NIA NIH HHS P01 AG001751NIDDK NIH HHS K23 DK099442NIH HHS S10 OD016201
6 · The paper itself

Abstract

backgroundLoss of mitochondrial function contributes to fatigue, exercise intolerance and muscle weakness, and is a key factor in the disability that develops with age and a wide variety of chronic disorders. Here, we describe the impact of a first-in-class cardiolipin-binding compound that is targeted to mitochondria and improves oxidative phosphorylation capacity (Elamipretide, ELAM) in a randomized, double-blind, placebo-controlled clinical trial.

methodsNon-invasive magnetic resonance and optical spectroscopy provided measures of mitochondrial capacity (ATPmax) with exercise and mitochondrial coupling (ATP supply per O2 uptake; P/O) at rest. The first dorsal interosseous (FDI) muscle was studied in 39 healthy older adult subjects (60 to 85 yrs of age; 46% female) who were enrolled based on the presence of poorly functioning mitochondria. We measured volitional fatigue resistance by force-time integral over repetitive muscle contractions.

resultsA single ELAM dose elevated mitochondrial energetic capacity in vivo relative to placebo (ΔATPmax; P = 0.055, %ΔATPmax; P = 0.045) immediately after a 2-hour infusion. No difference was found on day 7 after treatment, which is consistent with the half-life of ELAM in human blood. No significant changes were found in resting muscle mitochondrial coupling. Despite the increase in ATPmax there was no significant effect of treatment on fatigue resistance in the FDI.

conclusionsThese results highlight that ELAM rapidly and reversibly elevates mitochondrial capacity after a single dose. This response represents the first demonstration of a pharmacological intervention that can reverse mitochondrial dysfunction in vivo immediately after treatment in aging human muscle.

Indexed as

Adenosine TriphosphateMuscle, SkeletalOligopeptidesAgedAged, 80 and overDouble-Blind MethodExerciseFemaleHumansMaleMiddle AgedMitochondria, MuscleMuscle ContractionMuscle FatigueAdenosine Triphosphatearginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamideOligopeptides

Identifiers

PMID34264994
PMCPMC8282018
OpenAlexW3180296007

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.