RCT of Ghrelin in Stroke Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Stroke, Ischemic

Intervention / Treatment
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* Drug: Ghrelin


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This will be a phase 2 multicenter clinical trial with random treatment allocation, open label treatment and blinded endpoint assessment (PROBE design). The intervention contrast will be intravenous acylated ghrelin in addition to standard care (intervention group) vs. standard care alone (control group).
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ghrelin treatment<br>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<br>* 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.<br>|
| No Intervention: Standard care<br>Treatment in the standard group consists of local practices for the treatment of stroke, including intravenous thrombolysis, if indicated. | |

What is the study measuring?
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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 |
| --- | --- | --- |
| 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 | 
| Mortality | Mortality at 90 days | 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 | 
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Endovascular thrombectomy, Ghrelin