First registered human RCT of MOTS-c: Phase 2a insulin-sensitivity trial (NCT07505745)
Provenance: registered interventional RCT (recruiting — no results yet)
ClinicalTrials.gov record NCT07505745, confirmed on the registry (and mirrored at Veeva CTV and ICH-GCP). This appears to be the first registered, randomized, double-blind, placebo-controlled human trial of administered MOTS-c. Recruiting; no results.
Key findings
- NCT07505745 — Phase 2a, randomized 1:1 subcutaneous MOTS-c vs placebo, double-blind, placebo-controlled, in adults with prediabetes and overweight/obesity, all receiving standardized lifestyle counseling.
- Primary endpoint: change from baseline in OGTT-derived insulin sensitivity (Matsuda Index) after 12 weeks of treatment.
- Secondary endpoints: HbA1c, fasting glucose, 2-hour OGTT glucose, and immunogenicity. Safety followed through Week 16 (treatment-emergent adverse events).
- Rationale: MOTS-c (16-aa mitochondrial-derived peptide from the 12S rRNA ORF) regulates insulin sensitivity via skeletal-muscle AMPK activation in preclinical models; circulating levels decline with age and rise with exercise.
Why it matters for this base
- MOTS-C is a catalog peptide whose human evidence has been preclinical + observational only; this upgrades it to a registered Phase 2a RCT with a hard metabolic endpoint — the same “registered but unreported” credibility step the KB already tracks for BPC-157 (SOURCE-bpc157-hamstring-rct-nct07437547) and TB-500 (SOURCE-tb500-ascvd-rct-nct07487363).
- Timely: MOTS-c is simultaneously on the FDA PCAC 503A agenda for “obesity and osteoporosis” (SOURCE-fda-pcac-503a-peptide-review-2026) — trial + regulatory review moving in parallel.
- If it reads out positive, this becomes P0/P1 news for the Fat Loss / Metabolic and mitochondrial clusters.
Caveats
- Recruiting / registered only — no results. Registration ≠ efficacy or safety conclusion. Phase 2a is small and early. MOTS-c remains not FDA-approved; research/educational use only.
Corroborating sources
- ClinicalTrials.gov NCT07505745 (primary); Veeva Clinical Trials Vault; ICH-GCP registry mirror. Mechanistic background: Diabetes Metab J MOTS-c review; PMC9905433; Frontiers Physiol 2025 (T2D heart).