Serum biomarkers of postanoxic encephalopathy in relation to ghrelin treatment. A secondary analysis of the GRECO trial

Abstract

BACKGROUND AND AIM: In the Ghrelin in Coma (GRECO) trial, treatment with acyl-ghrelin in comatose patients after cardiac arrest was safe. This secondary analysis investigates the effect of acyl-ghrelin on circulating neuro-biomarkers. PRINCIPAL METHODS AND RESULTS: GRECO was a phase 2, double-blind, randomised, placebo-controlled trial of intravenous treatment with 600 µg acyl-ghrelin or placebo, twice daily for 7 days, in comatose patients after cardiac arrest. In 125 of 160 participants (65 intervention), serum samples were collected on days 0, 1, 3, and 7 to measure neuron-specific enolase (NSE), ubiquitin carboxyl hydrolase L1 (UCH-L1), soluble calcium binding protein 100 (S100), glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and Tau phosphorylated at threonine 181 (pTau181). Linear mixed-effect models showed a statistically significant treatment-interaction effect for GFAP on days 1 (estimate = 0.855, p = 0.015) and 3 (estimate = 1.017, p = 0.0037), indicating a smaller GFAP increase in the intervention group. There was no significant effect of acyl-ghrelin on the neuro-biomarkers on other timepoints, except on day 0 for S100, pTau181, and UCH-L1. MAJOR CONCLUSIONS: Acyl-ghrelin treatment during the first week after cardiac arrest was associated with less GFAP elevation in the first three days, suggesting reduced astroglial activation and/or damage. No other significant effects were found, except for S100, pTau181, and UCH-L1 on day 0, possibly indicating baseline imbalances. CLINICAL TRIAL REGISTRATION: Clinicaltrialsregister.eu; EUCTR2018-000005-23-NL.