The Multicenter Randomized trial of Ghrelin in anterior circulation ischemic stroke treated with endovascular thrombectomy (MR GENTLE) is a randomized phase 2 trial with a PROBE design. The primary objective of this study is to assess the effect of intravenous acyl-ghrelin – as a potential neuroprotective drug – on the severity of the neurological deficit at seven days after symptom onset in patients with acute ischemic stroke caused by large vessel occlusion of the anterior circulation and treated with EVT. Inclusion started in November 2024 and is expected to end in Q1/Q2 2026. The trial is registered with EU trial number: 2024-515705-26-00.
Rationale and aim
About half of the patients with acute ischemic stroke treated with endovascular thrombectomy (EVT) remains dependent or dies in the first 90 days. We hypothesise that treatment with acyl-ghrelin will improve early recovery and long-term functional outcome in these patients. Ghrelin is a naturally occurring hormone and mildly excitatory neurotransmitter that improved functional, histological, and cytological recovery in in vitro and in vivo ischemia-reperfusion models. Acyl-ghrelin (i.e., the bioactive form) has demonstrated safety in a range of populations, including patients with cardiovascular or neurodegenerative disease.
Study design
MR GENTLE is an investigator-initiated, phase 2, randomised clinical trial with open-label treatment and blinded endpoint assessment in eighty patients with acute ischemic stroke in the anterior circulation treated with EVT and a pre-EVT NIHSS score ≥ 10 in four centres in the Netherlands. Patients are randomised to intravenous acyl-ghrelin, 600µg twice daily for five days, started within six hours after stroke onset, in addition to standard care or to standard care alone. The primary outcome is the NIHSS score on day 7, adjusted for baseline characteristics. Secondary outcomes include infarct size on MRI (day 3), adverse events, and functional recovery at 90 days. Informed consent is obtained within 72 hours following randomization through a deferred consent procedure.
Study overview:
Study protocol and documents
Informed consent form legal representative
Informed consent form patient 2nd instance
Informed consent form patient deferred consent
Participating centers
Rijnstate Hospital, Arnhem – coordinating centre
UMC Utrecht, Utrecht
Isala, Zwolle
Medisch Spectrum Twente, Enschede
Principle investigators
Professor J. (Jeannette) Hofmeijer, MD, PhD (neurologist at Rijnstate hospital Arnhem)
Professor H.B. (Bart) van der Worp, MD, PhD (neurologist at UMC Utrecht)
C.J.B.A. (Clemens) Kersten, MD, PhD (neurologist at Isala Zwolle)
R.M. (Renate) Arntz, MD, PhD (neurologist at Medisch Spectrum Twente)
Coordinating investigator
Q.P.M. (Quinty) Omes, MD, PhD candidate University of Twente, coordinating investigator at Rijnstate hospital.
Contact
Quinty Omes – trial coordinator: qomes@rijnstate.nl
Jeannette Hofmeijer – PI: j.hofmeijer@utwente.nl
Study progress
Study start date: 22 November 2024
Expected study end date: 1 March 2026
Current number of inclusions (19-1-2026): 55
