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

Q P M Omes; S Nutma; A Beishuizen; P M G Filius; H B van der Worp; N A Foudraine; J G Krabbe; I A Strate; M J A M van Putten; J Hofmeijer

doi:10.1016/j.resuscitation.2026.110980

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

Q P M Omes^*
, S Nutma
, A Beishuizen
, P M G Filius
, H B van der Worp
, N A Foudraine
, J G Krabbe
, I A Strate
, M J A M van Putten
, J Hofmeijer
,

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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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.

Original language	English
Article number	110980
Journal	Resuscitation
Volume	220
Early online date	20 Jan 2026
DOIs	https://doi.org/10.1016/j.resuscitation.2026.110980
Publication status	Published - Mar 2026

Keywords

Ghrelin
Neuroprotection
Postanoxic encephalopathy
Serum biomarkers

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Serum biomarkers of postanoxic encephalopathy in relation to ghrelin treatment. A secondary analysis of the GRECO trialFinal published version, 514 KBLicence: CC BY

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Omes, Q. P. M., Nutma, S., Beishuizen, A., Filius, P. M. G., van der Worp, H. B., Foudraine, N. A., Krabbe, J. G., Strate, I. A., van Putten, M. J. A. M., Hofmeijer, J. (2026). Serum biomarkers of postanoxic encephalopathy in relation to ghrelin treatment. A secondary analysis of the GRECO trial. Resuscitation, 220, Article 110980. https://doi.org/10.1016/j.resuscitation.2026.110980

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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.",

keywords = "Ghrelin, Neuroprotection, Postanoxic encephalopathy, Serum biomarkers",

author = "Omes, \{Q P M\} and S Nutma and A Beishuizen and Filius, \{P M G\} and \{van der Worp\}, \{H B\} and Foudraine, \{N A\} and Krabbe, \{J G\} and Strate, \{I A\} and \{van Putten\}, \{M J A M\} and J Hofmeijer",

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year = "2026",

month = mar,

doi = "10.1016/j.resuscitation.2026.110980",

language = "English",

volume = "220",

journal = "Resuscitation",

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TY - JOUR

T1 - Serum biomarkers of postanoxic encephalopathy in relation to ghrelin treatment. A secondary analysis of the GRECO trial

AU - Omes, Q P M

AU - Nutma, S

AU - Beishuizen, A

AU - Filius, P M G

AU - van der Worp, H B

AU - Foudraine, N A

AU - Krabbe, J G

AU - Strate, I A

AU - van Putten, M J A M

AU - Hofmeijer, J

PY - 2026/3

Y1 - 2026/3

N2 - 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.

AB - 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.

KW - Ghrelin

KW - Neuroprotection

KW - Postanoxic encephalopathy

KW - Serum biomarkers

UR - https://www.scopus.com/pages/publications/105029115163

U2 - 10.1016/j.resuscitation.2026.110980

DO - 10.1016/j.resuscitation.2026.110980

M3 - Article

C2 - 41570882

SN - 0300-9572

VL - 220

JO - Resuscitation

JF - Resuscitation

M1 - 110980

ER -

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

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