Human study PLS-00121

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

Randomized controlled trial · 39 participants enrolled

Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

Only the abstract was available. Essential methods may be missing, which limits what can be judged.

Reports of this study

Every publication, registration and abstract describing this one study. Participants are counted once.

In vivo mitochondrial ATP production is improved in older adult skeletal muscle after a single dose of elamipretide in a randomized trial.primary · PloS one · 2021-07-15 · PMID 34264994 · DOI

Design and participants

Design: Randomized controlled trial
Population: Healthy older adults aged 60 to 85 years (46% female), enrolled because they had poorly functioning skeletal muscle mitochondria. The first dorsal interosseous muscle was studied.
Conditions: Age-related skeletal muscle mitochondrial dysfunction
Planned enrollment (registry): Not reported
Enrolled: 39
Randomized: Not reported
Completed follow-up: Not reported
Funding: Not stated in the record.
Authors’ conflicts: Not stated in the record.

Intervention and comparator

What each group received. Related peptides, analogs and combinations are never treated as the compound itself.

Elamipretide (intervention) · elamipretide · Elamipretide (ELAM), a mitochondria-targeted cardiolipin-binding peptide · infusion (2-hour) · Single dose given as a 2-hour infusion · Not reported assigned
Placebo (comparator) · Placebo · placebo · infusion (2-hour) · Single 2-hour infusion · Not reported assigned

What the authors reported

As stated in the sources. This is the authors’ account, not Peptide Library’s assessment.

Mitochondrial energetic capacity (ATPmax) during exercise

unclear outcome · surrogate · Immediately after the 2-hour infusion, and day 7 · Non-invasive magnetic resonance and optical spectroscopy of the first dorsal interosseous muscle; reported as change (ΔATPmax) and percent change (%ΔATPmax)

Elamipretide vs Placebo: narrative, p = 0.055 — ΔATPmax was higher with elamipretide than placebo immediately after the infusion
Elamipretide vs Placebo: narrative, p = 0.045 — %ΔATPmax was higher with elamipretide than placebo immediately after the infusion
Elamipretide vs Placebo: narrative — No difference between groups on day 7 after treatment

Resting mitochondrial coupling (P/O, ATP supply per O2 uptake)

unclear outcome · surrogate · After treatment (not further specified) · Magnetic resonance and optical spectroscopy at rest

Elamipretide vs Placebo: narrative — No significant changes in resting muscle mitochondrial coupling

Volitional fatigue resistance

unclear outcome · patient-important · After treatment (not further specified) · Force-time integral over repetitive contractions of the first dorsal interosseous muscle

Elamipretide vs Placebo: narrative — No significant effect of treatment on fatigue resistance

Adverse events

None reported. That is not evidence of safety.

Monitoring: Not reported in the abstract.

The authors concluded (paraphrased): A single elamipretide dose rapidly and reversibly raised muscle mitochondrial capacity in older adults. The authors present this as the first pharmacological reversal of mitochondrial dysfunction in aging human muscle in vivo.

Peptide Library’s assessment

An automated assessment, made by AI separately from the authors’ conclusions and not reviewed by a person. How risk of bias is assessed.

Limitations

abstract only: Only the abstract is available, so randomization, allocation, attrition and arm sizes cannot be checked.
small or imprecise: Only 39 participants were studied, and the main ATPmax result is borderline (P = 0.055 for change, P = 0.045 for percent change).
inappropriate endpoint: The positive finding is a spectroscopic surrogate (ATPmax). The functional fatigue-resistance outcome showed no significant effect.
short follow up: A single dose was assessed only immediately after infusion and on day 7. The effect had disappeared by day 7.
inappropriate population: Participants were healthy older adults, not people with Barth syndrome or primary mitochondrial myopathy.
selective reporting: Two versions of the ATPmax metric are reported, one just above and one just below 0.05, which raises concern about selective emphasis.
other: No adverse events, tolerability or discontinuation data are reported in the abstract.

Mitochondrial energetic capacity (ATPmax) during exercise: Some concerns (Cochrane RoB 2)

Risk of bias in one result of a randomized trial, judged in five domains.

Domain judgments
Randomization process	Some concerns	The abstract states the trial was randomized but does not describe sequence generation, allocation concealment or baseline balance.
Deviations from intended interventions	Some concerns	The trial is described as double-blind and placebo-controlled, but infusion delivery and any deviations are not reported.
Missing outcome data	Some concerns	Numbers randomized, analyzed and lost are not reported in the abstract.
Measurement of the outcome	Some concerns	Outcome is an objective spectroscopy measure under double-blinding, but assessor procedures are not detailed in the abstract.
Selection of the reported result	Some concerns	Both absolute and percent ATPmax change are reported with borderline p-values, and no prespecified analysis plan is cited.

Blinded RCT with an objective measure, but reporting is abstract-only and the choice among analyses is unclear.

Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · RoB 2 (2019-08-22) · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

Resting mitochondrial coupling (P/O, ATP supply per O2 uptake): Some concerns (Cochrane RoB 2)

Risk of bias in one result of a randomized trial, judged in five domains.

Domain judgments
Randomization process	Some concerns	Randomization is stated, but methods and baseline balance are not described in the abstract.
Deviations from intended interventions	Some concerns	Double-blind placebo control is reported, but adherence and deviations are not described.
Missing outcome data	Some concerns	Analyzed numbers and dropouts are not given in the abstract.
Measurement of the outcome	Some concerns	Objective spectroscopic measure with blinding, but measurement details are not reported in the abstract.
Selection of the reported result	Some concerns	Reported only narratively as no significant change, without estimates or a prespecified analysis plan.

Abstract-only reporting of a blinded RCT leaves several domains unclear.

Volitional fatigue resistance: Some concerns (Cochrane RoB 2)

Risk of bias in one result of a randomized trial, judged in five domains.

Domain judgments
Randomization process	Some concerns	Randomization is stated, but sequence generation and concealment are not described in the abstract.
Deviations from intended interventions	Some concerns	Double-blind design is stated, but deviations from the intended intervention are not reported.
Missing outcome data	Some concerns	Number of participants analyzed for fatigue resistance is not reported.
Measurement of the outcome	Some concerns	Volitional force-time integral depends on participant effort; blinding is stated, but procedures are not described.
Selection of the reported result	Some concerns	Result is given only narratively as non-significant, without timepoint or estimate in the abstract.

Blinded RCT, but abstract-only reporting and an effort-dependent measure leave concerns.

Claims this study informs

Improves function in Barth syndrome: not eligible (wrong population) for “Muscle strength, exercise capacity and fatigue”
Improves exercise capacity in primary mitochondrial myopathy: not eligible (wrong population) for “Six-minute walk distance and fatigue”
Is safe for human administration: not eligible (insufficient data) for “Adverse events, including injection-site reactions, and discontinuations”

Where each value comes from

arms: PMID 34264994, abstract (Results, sentence 1) · extracted by AI (automated, not verified by a person) · abstract only
author_conclusion: PMID 34264994, abstract (Conclusions, sentences 1-2) · extracted by AI (automated, not verified by a person) · abstract only
design: PMID 34264994, abstract (Background, sentence 2) · extracted by AI (automated, not verified by a person) · abstract only
limitations: PMID 34264994, abstract (Results, sentences 1-4) · extracted by AI (automated, not verified by a person) · abstract only
outcomes: PMID 34264994, abstract (Methods, sentences 1 and 3) · extracted by AI (automated, not verified by a person) · abstract only
participants: PMID 34264994, abstract (Methods, sentence 2) · extracted by AI (automated, not verified by a person) · abstract only
population: PMID 34264994, abstract (Methods, sentence 2) · extracted by AI (automated, not verified by a person) · abstract only
results: PMID 34264994, abstract (Results, sentences 1-4) · extracted by AI (automated, not verified by a person) · abstract only

Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.

These assessments describe published research. Records marked automated were produced by AI under the published methodology and have not been reviewed by a person; they can contain errors. None of this is medical advice, not a statement about any product’s safety for human use, and not a regulatory approval. Peptide Library’s vendor and partner relationships play no part in them (editorial independence).