MR GENTLE-multicentre randomised controlled trial of ghrelin in anterior circulation ischaemic stroke treated with...

About half of the patients with acute ischaemic stroke treated with endovascular thrombectomy (EVT) remains dependent or dies in the first 90 days. Ghrelin is a naturally occurring hormone and mildly excitatory neurotransmitter that improved functional, histological, and cytological recovery in in vitro and in vivo ischaemia-reperfusion models. Acylated ghrelin (i.e. the bioactive form) has shown safety in a range of populations, including patients with cardiovascular or neurodegenerative disease. We hypothesise that treatment with acylated ghrelin improves early recovery and long-term functional outcome in patients with ischaemic stroke treated with EVT.

We propose an investigator-initiated, phase 2, randomised, clinical trial with open-label treatment and blinded endpoint assessment in 80 patients with anterior circulation ischaemic stroke treated with EVT and a pre-EVT National Institutes of Health Stroke Scale (NIHSS) score ≥ 10. Patients will be randomised to intravenous acylated ghrelin, 600 µg twice daily for 5 days and started within 6 h of symptom onset, in addition to standard care vs. standard care alone. The primary outcome is the NIHSS score on day 7 adjusted for pre-EVT NIHSS and other relevant baseline characteristics. Secondary outcomes include infarct size on MRI at day 3, adverse events, and functional recovery at 90 days. The primary analysis will be a single comparison between the treatment groups of the primary outcome according to the intention-to-treat principle. The primary effect variable will be the adjusted beta for the difference in NIHSS score, estimated with multi-variable linear regression analysis.

If administration of acylated ghrelin is found safe and potentially effective in patients with ischaemic stroke treated with EVT, this study can inform the sample size calculation for a subsequent randomised phase 3 trial to assess efficacy.

The trial has been approved and registered on ClinicalTrials.gov (NCT05726240). The first patient has been included in November 2024.