PMID-23559086 – Macimorelin-Stimulated GH Test Validation Phase 2
Garcia JM, Swerdloff R, Wang C, et al. Macimorelin (AEZS-130)-stimulated growth hormone (GH) test: validation of a novel oral stimulation test for the diagnosis of adult GH deficiency. J Clin Endocrinol Metab. 2013;98(6):2422-2429.
Quick Reference
| Property | Value |
|---|---|
| PMID | 23559086 |
| DOI | 10.1210/jc.2013-1157 |
| Year | 2013 |
| Journal | Journal of Clinical Endocrinology & Metabolism |
| Study Type | RCT (Phase 2 Diagnostic Accuracy Study) |
| Evidence Level | II |
| Sample | n=68 (39 AGHD patients + 29 healthy controls) |
| Peptide(s) Studied | Macimorelin |
Key Findings
- First clinical validation of oral macimorelin as a diagnostic test for adult GH deficiency
- Macimorelin (0.5 mg/kg oral) stimulated a robust GH response in healthy controls but a blunted response in AGHD patients
- ROC analysis yielded optimal GH cut-point of 2.7 ng/mL with 82% sensitivity, 92% specificity, and 13% misclassification rate
- GH peak typically occurred at 30-45 minutes post-dose, making this a convenient 90-minute office-based test
- Well tolerated: most common adverse events were dysgeusia (taste alteration), dizziness, and headache (all mild)
- No serious adverse events; no significant hemodynamic changes (unlike ITT-induced hypoglycemia)
- Macimorelin is a non-peptide peptidomimetic that acts as a GHS-R1a (ghrelin receptor) agonist
Study Design
Open-label, Phase 2, multicenter diagnostic study. Subjects with confirmed or suspected adult GH deficiency and healthy matched controls received a single oral dose of macimorelin (0.5 mg/kg dissolved in water). Serum GH measured at 0, 15, 30, 45, 60, and 90 minutes. Compared to ITT and GHRH+arginine as reference standards. ROC analysis performed to determine optimal diagnostic cut-points.
Limitations
- Moderate sample size (n=68)
- Single oral dose — no assessment of repeated testing variability in this study
- Obese subjects may have attenuated GH response (not fully stratified by BMI)
- Phase 2 study — further validation needed (subsequently done in Phase 3, PMID: 29860473)
- Comparison primarily against ITT — GHRH+arginine comparisons were limited
Clinical Relevance
This Phase 2 validation study established the proof-of-concept for oral GH stimulation testing using a ghrelin receptor agonist. The study is clinically significant because it demonstrated that GHS-R1a activation via oral administration produces a diagnostically useful GH response within 90 minutes — eliminating the need for IV access, insulin-induced hypoglycemia (ITT), or combination IV infusions (GHRH+arginine). For the vault, this study links to the GH axis category by validating the ghrelin receptor as a reliable switch for pituitary GH secretion. The mechanism is identical to ipamorelin and MK-677 (both GHS-R1a agonists), but macimorelin is optimized for single-dose diagnostic use rather than chronic GH elevation.
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#research #RCT #macimorelin #evidence-level-II #gh-axis