Evidence map›Paper›PMID 29500292›Full record

Trial reportNeurology2018

Randomized dose-escalation trial of elamipretide in adults with primary mitochondrial myopathy.

Amel Karaa, Richard Haas, Amy Goldstein, Jerry Vockley, W Douglas Weaver, Bruce H Cohen

Erratum issuedOpen access · hybridAbstract readClinical Trial, Phase IClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Neurology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 88 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
88citing papers in PubMed, 1 pooled it
7.5field-weighted citation impact, top 2% 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

88 citing papers in PubMed, 1 synthesis or guideline pooled it, 143 citations in OpenAlex.

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28 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 4 institutions in 1 country.

Amel KaraaFrom the Genetics Unit (A.K.), Massachusetts General Hospital, Boston; UC San Diego School of Medicine (R.H.), La Jolla, CA; Children's Hospital of Pittsburgh (A.G., J.V.), PA; Stealth BioTherapeutics (W.D.W.), Newton, MA; and Akron Children's Hospital (B.H.C.), OH. akaraa@mgh.harvard.edu.
Richard HaasFrom the Genetics Unit (A.K.), Massachusetts General Hospital, Boston; UC San Diego School of Medicine (R.H.), La Jolla, CA; Children's Hospital of Pittsburgh (A.G., J.V.), PA; Stealth BioTherapeutics (W.D.W.), Newton, MA; and Akron Children's Hospital (B.H.C.), OH.
Amy GoldsteinFrom the Genetics Unit (A.K.), Massachusetts General Hospital, Boston; UC San Diego School of Medicine (R.H.), La Jolla, CA; Children's Hospital of Pittsburgh (A.G., J.V.), PA; Stealth BioTherapeutics (W.D.W.), Newton, MA; and Akron Children's Hospital (B.H.C.), OH.
Jerry VockleyFrom the Genetics Unit (A.K.), Massachusetts General Hospital, Boston; UC San Diego School of Medicine (R.H.), La Jolla, CA; Children's Hospital of Pittsburgh (A.G., J.V.), PA; Stealth BioTherapeutics (W.D.W.), Newton, MA; and Akron Children's Hospital (B.H.C.), OH.
W Douglas WeaverFrom the Genetics Unit (A.K.), Massachusetts General Hospital, Boston; UC San Diego School of Medicine (R.H.), La Jolla, CA; Children's Hospital of Pittsburgh (A.G., J.V.), PA; Stealth BioTherapeutics (W.D.W.), Newton, MA; and Akron Children's Hospital (B.H.C.), OH.
Bruce H CohenFrom the Genetics Unit (A.K.), Massachusetts General Hospital, Boston; UC San Diego School of Medicine (R.H.), La Jolla, CA; Children's Hospital of Pittsburgh (A.G., J.V.), PA; Stealth BioTherapeutics (W.D.W.), Newton, MA; and Akron Children's Hospital (B.H.C.), OH.
Akron Children's Hospital · USStealth BioTherapeutics (United States) · USChildren's Hospital of Pittsburgh · USMassachusetts General Hospital · US

Funding

The North American Mitochondrial Disease Consortium (NAMDC)U54NS078059 · NINDS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI HIRANO, MICHIO · 2011 to 2023
$17.5M
NINDS NIH HHS U54 NS078059
6 · The paper itself

Abstract

objectiveTo assess the safety and efficacy of elamipretide, an aromatic-cationic tetrapeptide that readily penetrates cell membranes and transiently localizes to the inner mitochondrial membrane where it associates with cardiolipin, in adults with primary mitochondrial myopathy (PMM).

methodsA Study Investigating the Safety, Tolerability, and Efficacy of MTP-131 for the Treatment of Mitochondrial Myopathy (MMPOWER) was a phase I/II multicenter, randomized, double-blind, placebo-controlled trial of elamipretide in 36 participants with genetically confirmed PMM. Participants were randomized to intravenous elamipretide (0.01, 0.1, and 0.25 mg/kg/h or placebo for 2 hours in a dose-escalating sequence). The primary efficacy measure was the change in distance walked in the 6-minute walk test (6MWT) after 5 days of treatment. Other efficacy measures included changes in cardiopulmonary exercise testing parameters, in participant-reported symptoms, and in serum and urinary biomarkers. Safety, tolerability, and pharmacokinetics were also measured.

resultsParticipants who received the highest dose of elamipretide walked a mean of 64.5 m farther at day 5 compared to a change of 20.4 m in the placebo group (

conclusionsElamipretide increased exercise performance after 5 days of treatment in patients with PMM without increased safety concerns. These findings, as well as additional functional and patient-reported measures, remain to be tested in larger trials with longer treatment periods to detect other potential therapeutic benefits in individuals affected by this condition. CLASSIFICATION OF EVIDENCE: This trial provides Class I evidence that for patients with PMM, elamipretide improved the distance walked on the 6MWT.

Indexed as

Administration, IntravenousAdultDose-Response Relationship, DrugDouble-Blind MethodFemaleHumansMaleMitochondrial MyopathiesNeuromuscular AgentsOligopeptidesTreatment OutcomeWalk Testarginyl-2,'6'-dimethyltyrosyl-lysyl-phenylalaninamideNeuromuscular AgentsOligopeptides

Identifiers

PMID29500292
PMCPMC5890606
OpenAlexW2793770005

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.