Exploring the Effect of Lactate Administration After Ischemic Stroke on Brain Metabolism

Study Overview
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Brief Summary
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In this exploratory randomized double blind placebo controled trial, lactate solution or placebo will be administered to acute ischemic stroke patients selected for endovascular treatment (EVT) without intravenous thrombolysis. The treatment will be administered within one hour after EVT. Primary outcome measures will be lactate and metabolite concentrations in the ischemic lesion, in the penumbra and contralaterally, evaluated by magnetic resonance spectroscopy(MRS). Secondary outcome measures will be evolution of the ischemic penumbra, clinical outcome at 3 months.The trial will end when 10 patients per group have completed the study.

Detailed Description
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This is an exploratory randomized double blind placebo controled trial on acute ischemic stroke patients. Lactate solution or placebo will be administered to acute ischemic stroke patients selected for endovascular treatment (EVT) without intravenous thrombolysis. Magnetic resonance spectroscopy will be performed before EVT to measure metabolite concentrations in the ischemic core, penumbra and in the contralateral hemisphere. The treatment will be administered within one hour after EVT. As soon as the patient is stabilized, she/he will undergo an additional magnetic resonance imaging (MRI) with magnetic resonance spectroscopy (MRS). MRS will also be performed during the control MRI after 24 hours. Neurological deficits will be evaluated on admission, at 24 hours using the National Institute of Health Stroke Scale (NIHSS), and at 3 months, with both NIHSS and the modified Rankin scale. Primary outcome measures will be lactate and metabolite concentrations changes in the ischemic lesion, in the penumbra and the contralateral side, evaluated by magnetic resonance spectroscopy after intervention compared to baseline MRS values. Secondary outcome measures will be evolution of the ischemic penumbra and clinical outcome at 3 months. The trial will end when 10 patients per group have completed the study.

Official Title
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Exploration de l'Effet Sur le métabolisme cérébral de l'Administration de Lactate après Accident Vasculaire cérébral Chez l'Homme (French Title)

Conditions
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Stroke, Acute

Intervention / Treatment
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* Drug: Lactate
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Acute ischemic stroke with arterial occlusion affecting middle cerebral artery (segment M1or segment 2) or internal carotid artery (T-type or L-type occlusion) selected for EVT not eligible for intravenous thrombolysis (IVT) Moderate to severe stroke (NIHSS > or = 4), and preadmission mRS > or = 3) Perfusion - diffusion mismatch Obtain consent from independent Doctor Randomisation criteria If possible oral consent from patient or relatives Treatment administration possible within 1h from EVT Exclusion Criteria: Rapid neurological recovery Clinically unstable patient Contraindications to MRI Blood Na+ > 155 mmol/l or plasma osmolality > 320 mosmol/l Medical history of traumatic brain injury (TBI), neurodegenerative disease, intracranial hemorrhage, cerebral aneurysm, brain tumour Medical history of psychiatric disorders Liver insufficiency Heart failure Pregnancy (pregnancy test required in women aged under 50 unless patient or relatives indicate that the patient is not pregnant) Participation in another clinical trial in the last 30 days Lack of consent of an independent Doctor

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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: placebo<br>patients will be injected with placebo | Drug: Placebo<br>* Intravenous injection (20 min)<br>* Other names: Saline solution administration;|
| Active Comparator: Lactate<br>patients will be injected with lactate solution | Drug: Lactate<br>* Intravenous injection (20 min), 300 mmol/L, 1mmol/Kg body weight,<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Does the administered lactate reach the brain | Measurement of lactate and other metabolites in lesion, penumbra, contralateral side using magnetic resonance spectroscopy measured after intervention and compared to baseline values. After intervention, the MRS will be performed as soon as possible considering that these patients have an EVT under general anesthesia and need to be stabilised after the EVT and study treatment intervention before the MRS. | Measurement after intervention (as soon as the patient condition allows performing an MRI; estimated between 1 and 2 hours) | 
| Does the administered lactate persist in the brain at 24 hours | Measurement of lactate and other metabolites in lesion, penumbra, contralateral side using magnetic resonance spectroscopy measured at 24 hours and compared to baseline values. | The MRS will be performed during the routine clinical MRI approximately 24 hours after EVT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effect of lactate on neuronal death after intervention | Assessment of N-acetyl aspartate (NAA), a neuronal marker, using MRS and compared to baseline values, in the ischemic core and in the ischemic penumbra. | Measurement after intervention (as soon as the patient condition allows performing an MRI; estimated between 1 and 2 hours) | 
| Effect of lactate on neuronal death at 24 hours | Assessment of N-acetyl aspartate (NAA), a neuronal marker, using MRS and compared to baseline values, in the ischemic core and in the ischemic penumbra. | Measurement at during the routine control MRS, approximately 24 hours after EVT | 
| Effect of lactate on evolution of lesion at 24 hours | Assessment of lesion using diffusion weighted Imaging (DWI) compared to baseline value | At 24 hours | 
| Effect of lactate on evolution of penumbra at 24 hours | Check impact of intervention on the penumbra using perfusion weighted imaging (PWI) at 24 hours compared to baseline | This evaluation will be based on the routine MRI evaluation performed approximately 24 hours after EVT | 
| Clinical outcome at 24 hours | Evolution of the neurological score (NIHSS) and compared to baseline assessment | at 24 hours | 
| Clinical outcome at 3 months | Evolution of neurological score (NIHSS) compared to baseline value | Measurement at follow up (3 months) | 
| Handicap at 3 months | Evolution of neurological handicap (mRS) compared to baseline value | Measurement at follow up (3 months) |