RCT of Ghrelin in Stroke Patients (MR GENTLE)

Multicentre Randomized Trial of Ghrelin in Anterior Circulation Ischemic Stroke Treated With Endovascular Thrombectomy. A Randomized Phase 2 Trial

About half of the patients with acute ischemic stroke treated with endovascular thrombectomy (EVT) remain dependent on the help of others or die in the first 90 days. We hypothesize that treatment with ghrelin, started in the first six hours after stroke onset, improves early recovery and long-term functional outcome in these patients. Ghrelin is a naturally occurring hormone and mildly excitatory neurotransmitter also known as the 'hunger hormone.' Treatment with acylated ghrelin consistently improved functional and histological recovery in in vitro and in vivo models of ischemic stroke.

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke, Ischemic
• Intervention / Treatment: Drug: Ghrelin

Detailed Description

We will include 80 patients with acute ischemic stroke caused by large vessel occlusion of the anterior circulation, eligible for EVT. The study population will be drawn from adult patients with acute ischemic stroke treated with EVT at UMC Utrecht, Rijnstate, MST or Isala.

Treatment in the intervention group will consist of intravenous acylated ghrelin, 600micrg dissolved in 50cc normal saline, by bolus (short term) infusion in 30 minutes, twice daily, for five days. This treatment will be additional to standard treatment, including intravenous thrombolysis, if indicated.

• Study Type: Interventional
• Enrollment (Estimated): 80
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Jeannette Hofmeijer, MD, PhD; Phone Number: 0880058877; Email: jhofmeijer@rijnstate.nl
• Study Contact Backup: Name: Daphne van der Veen, MSc; Email: vascularsurgery@rijnstate.nl

Study Locations

• Netherlands
  • Enschede, Netherlands
    • Medisch Spectrum Twente
    • Contact: Renate Arntz; Email: Renate.Arntz@mst.nl
    • Principal Investigator: Renate Arntz
  • Utrecht, Netherlands
    • University Medical Center Utrecht
    • Contact: Bart van der Worp; Email: H.B.vanderWorp@umcutrecht.nl
    • Principal Investigator: Bart van der Worp
  • Zwolle, Netherlands
    • Isala

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• a clinical diagnosis of acute ischemic stroke, caused by intracranial large vessel occlusion of the anterior circulation (distal intracranial carotid artery or middle (M1/proximal M2) cerebral artery) confirmed by neuro-imaging (CTA or MRA),
• treatment with EVT, defined as groin puncture in the angio suite,
• CT or MRI ruling out intracranial hemorrhage,
• a pre-EVT score of at least 10 on the NIHSS,
• age of 18 years or older,
• written informed consent (deferred).

Exclusion Criteria:

• pre-stroke disability defined as mRS ≥ 2,
• life expectancy shorter than one year,
• child-bearing potential.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ghrelin treatment; Treatment in the intervention group will consist of intravenous acylated ghrelin, 600micrg dissolved in 50cc normal saline, by bolus (short term) infusion in 30 minutes, twice daily, for five days. This treatment will be additional to standard treatment, including intravenous thrombolysis, if indicated.	Drug: Ghrelin; Treatment in the intervention group will consist of intravenous acylated ghrelin, 600micrg dissolved in 50cc normal saline, by bolus (short term) infusion in 30 minutes, twice daily, for five days. This treatment will be additional to standard treatment, including intravenous thrombolysis, if indicated.
No Intervention: Standard care; Treatment in the standard group consists of local practices for the treatment of stroke, including intravenous thrombolysis, if indicated.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
National Institutes of Health Stroke Scale score	The primary outcome measure is the score on the National Institutes of Health Stroke Scale at seven days (±1) after stroke onset or at discharge, if earlier. The NIHSS is a continuous scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.	7 days after stroke onset

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mortality	Mortality at 90 days	90 days after stroke onset
Blood glucose levels	Blood glucose levels at days 1-7 (or until discharge)	Days 1-7 after stroke onset
Blood pressure	Blood pressure at days 1-7 (or until discharge)	Days 1-7 after stroke onset
Body temperature	Body temperature at days 1-7 (or until discharge)	Days 1-7 after stroke onset
Modified Rankin Scale score	The score on the Modified Rankin Scale at 90 days after stroke onset. The mRS is an ordinal hierarchical scale that describes disabilities encountered post stroke, incorporating six categories from 0 (complete recovery) up to and including 5 (severe disability). 'Death' is assigned a score of 6 .	90 days after stroke onset
National Institutes of Health Stroke Scale score	Scores on National Institutes of Health Stroke Scale at 24 hours after stroke onset. The NIHSS is a continuous scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit. The NIHSS is a continuous scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.	24 hours after stroke onset
National Institutes of Health Stroke Scale score	Scores on National Institutes of Health Stroke Scale at 72 hours after stroke onset. The NIHSS is a continuous scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit. The NIHSS is a continuous scale to evaluate the severity of stroke by assessing a patient's performance. Scores range from 0 to 42, with higher scores indicating a more severe deficit.	72 hours after stroke onset
Telephonic Montreal Cognitive Assessment	Score on the telephone version of the Montreal Cognitive Assessment at 90 days. The MoCA 5-minute protocol consists of 4 subtests examining 5 cognitive domains, including attention, verbal learning and memory, executive functions/language, and orientation. Total scores of the MoCA 5-minute protocol range between 0 and 30 with lower scores indicating a better cognition.	90 days after stroke onset
Infarct size	Infarct size at 72 hours (based on Magnetic resonance imaging measurements)	72 hours after stroke onset

Collaborators and Investigators

• Sponsor: Rijnstate Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2023
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2024

Study Registration Dates

• First Submitted: February 1, 2023
• First Submitted That Met QC Criteria: February 1, 2023
• First Posted (Actual): February 13, 2023

Study Record Updates

• Last Update Posted (Actual): July 25, 2023
• Last Update Submitted That Met QC Criteria: July 22, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: Ghrelin; Endovascular thrombectomy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke; Ischemic Stroke
• Other Study ID Numbers: MR GENTLE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No