Peptide LibraryMuscle strength, exercise capacity and fatigue
Insufficient information to assessPatient-important outcome · 2 studies · 31 participants
Not enough evidence to tell
The certainty of evidence that elamipretide improves muscle strength, exercise capacity or fatigue in Barth syndrome is very low. In the only placebo-controlled trial, which had just 12 patients, elamipretide did not clearly beat placebo on its main measures. Improvements were seen later, when patients knew they were receiving the drug and when they were compared with past untreated patients. Such comparisons can easily overstate benefits, so whether elamipretide truly helps remains uncertain.
What the research measured: In the randomized crossover (12 patients, 12-week periods), the primary endpoints, 6-minute walk distance and BTHS-SA symptom score, were not met versus placebo. In the open-label extension, 6MWT improved by +95.9 m (p=0.024) and BTHS-SA by -2.1 points (p=0.031) at 36 weeks, with reported improvements in knee extensor strength and global impression. A propensity-score comparison of 8 extension patients with 19 natural history controls reported LS mean differences in 6MWT of 79.7 m (week 64) and 91.0 m (week 76), and in handheld dynamometry strength of 40.8 N and 56.7 N.
What remains unknown: There are no larger, longer placebo-controlled trials. Fatigue was not measured directly as a separate outcome. Safety and adverse event data were not reported in these records. Effects in different age groups and disease severities are unknown, and the full trial methods could not be checked because only abstracts were available.
Reviewers’ note: At least one included study has no risk-of-bias assessment, so no certainty rating is given.
How the certainty was judged
| Domain | Judgment | Why |
|---|---|---|
| Starting level | — | |
| Risk of bias | — | The only randomized placebo-controlled evidence (crossover, 12 subjects) did not meet its primary endpoints, and the positive results come from open-label, uncontrolled extension or a retrospective natural history comparison. Both studies were abstract-only, effort-dependent or self-reported outcomes were unblinded, and no formal risk-of-bias judgments were available. |
| Inconsistency | — | In the randomized placebo-controlled part, the 6MWT and symptom primary endpoints were not met. The open-label extension and the natural history comparison reported large improvements. The controlled and uncontrolled evidence point in different directions. |
| Indirectness | — | The study with significant between-group differences used untreated historical natural history controls, not placebo. The open-label extension has no comparator. Only the crossover part 1 directly matches the PICO, and it was null on its primary endpoints. |
| Imprecision | — | Only 12 patients were randomized and 8 reached 36 weeks of the extension. No effect estimate or confidence interval is reported for the placebo-controlled comparison. The historical-control study had 8 treated patients, who likely overlap with the trial. |
| Publication bias | — | Only two small related studies were found, and no unpublished registered trials were identified in the records. Publication bias could not be formally assessed. |
Included studies
- Natural history comparison study to assess the efficacy of elamipretide in patients with Barth syndrome. (Retrospective cohort)
- A phase 2/3 randomized clinical trial followed by an open-label extension to evaluate the effectiveness of elamipretide in Barth syndrome, a genetic disorder of mitochondrial cardiolipin metabolism. (Randomized controlled trial, 12 participants)
Version 1 · published November 8, 2026 · evidence through November 8, 2026 · research snapshot 2026.1.1 · methodology ev-1 · GRADE (handbook, 2013) · Automated assessment by AI (claude-opus-5-5 and claude-sonnet-5-5), not reviewed by a person.