MEPI-AVC: Effects of Mepivacaine on the Neurological Sequelae of Cerebral Infarction
Study Details
Study Description
Brief Summary
A patient, suffering from cortical blindness after a bi-occipital infarction 1 year earlier, regained near-normal vision in the right visual hemifield a few minutes after subcutaneous administration of mepivacaine. The effect was maintained for several days, and was repeated with each injection of mepivacaine. This clinical improvement is associated with functional changes in the peri-lesional areas on resting-state functional MRI.
The investigator team hypothesizes that in some patients with chronic neurological symptoms of stroke, the investigator team will observe a favorable response to subcutaneous mepivacaine injection.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
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Phase 2 |
Detailed Description
A patient, suffering from cortical blindness after a bi-occipital infarction 1 year earlier, regained near-normal vision in the right visual hemifield a few minutes after subcutaneous administration of mepivacaine. The effect was maintained for several days, and was repeated with each injection of mepivacaine. This clinical improvement is associated with functional changes in the peri-lesional areas on resting-state functional MRI. The investigator team hypothesizes that in some patients with chronic neurological symptoms of stroke, investigator team will observe a favorable response to subcutaneous mepivacaine injection.
The team will include patients with clinically significant sequelae of ischemic stroke, as was the case with the initial patient. In addition,
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The team hypothesizes that the mechanism of action is not specific to the visual cortex, and therefore should not be limited to visual scotomas
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It is also preferable to consider only deficits that can be objectively quantified in a sufficiently reliable way to be able to evaluate the effect of the treatment
The investigator teamwill therefore include patients with sequelae of at least one of the following three types:
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motor deficit: score =< 56 on the Fugl-Meyer scale, minimal deficit allowing to observe an improvement of 4 points
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aphasia: score >= 4 on the Aphasia Rapid Test (ART) , minimal deficit allowing to observe an improvement of 4 points
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visual scotoma: observable on a clinical assessment of the visual field "on confrontation"
Only patients more than 30 days after the occurrence of the stroke will be included. Indeed, the rapid recovery phase after a stroke lasts about 3 weeks and it is difficult to interpret rapid clinical changes and to attribute them to the treatment (since investigator team do not know the time of onset of the effect of mepivacaine) over this temporal period.
Mepivacaine will be administered as a single injection, subcutaneously, at a dose of 3 mL of mepivacaine hydrochloride (20 mg/mL), or 60mg. If mepivacaine is effective, research participants will experience a temporary reduction in neurological symptoms.
Time course of experiment
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Signing of consent
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Verification of inclusion and exclusion criteria (1h)
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ECG for all patients
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Urine dipstick if female of childbearing age
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Motor, language and visual field scales, depending on the deficit(s) present
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Blood sampling
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Evaluation of the neurological deficit before treatment (1h)
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VAS to evaluate the intensity of symptoms by the patient
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NIHSS
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MRI n°1 (duration 45 min to 1h)
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Administration of mepivacaine 7 Evaluation of the neurological deficit after treatment, at T= 30 +/- 15 minutes after administration (duration 1h)
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Motor, language and visual field scales, depending on the deficit(s) present
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VAS to evaluate the intensity of the symptoms by the patient
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NIHSS
8/ MRI n°2 (duration 30 to 45min) 1h30 after administration 9/ Call of the patient 1 week later for follow-up of SAEs and evaluation of the duration of the effect, if any.
Brain imaging
MRI will be performed on a SIEMENS 3 Tesla machine, without injection of contrast medium. The duration of the MRI will be approximately 45 minutes to one hour for MRI n°1 (baseline) and 30 to 45 minutes for MRI n°2 performed after the injection of mepivacaine.
MRI acquisitions will include the following sequences:
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T1 (only during MRI n°1 in baseline)
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FLAIR (only during baseline MRI n°1)
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Diffusion sequence (multishell, multiband)
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Perfusion sequence (Arterial Spin Labelling, ASL)
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Resting state BOLD sequence
Drug treatment :
Mepivacaine will be administered:
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Subcutaneously
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In the shoulder on the non-dominant side, or on the non-deficient side in case of hemiplegia
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Dose: 3 mL of mepivacaine hydrochloride (20 mg/mL), or 60mg
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With at disposal
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Resuscitation equipment (in particular, a source of oxygen)
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lipid emulsion to be administered in case of intoxication with clinical signs of neurotoxicity or cardiotoxicity
Genetic samples :
The gene coding for brain-derived neurotrophic factor (BDNF) is of particular interest. BDNF is a protein that contributes to neurogenesis and neuronal differentiation, participates in the creation of new synapses and influences the survival of existing neurons. It is thus currently considered as a crucial element influencing brain plasticity . This could also be an explanatory factor in identifying responders to mepivacaine.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Mepivacaine arm mepivacaine injection |
Drug: Carbocaine Injectable Product
One injection per patient
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Outcome Measures
Primary Outcome Measures
- improvement of clinical scores [1 Day]
The response is defined as an improvement 1h (+/- 30min) after injection, compared to the evaluation before mepivacaine injection, on at least one of the clinical scores specific to the symptoms considered (language, motor skills, visual field)
Secondary Outcome Measures
- language-related symptoms [1 Day]
Relative change, in percentage, in the number of correctly named images on a standardized battery (DO80) between pre- and post-injection to measure language-related symptoms.
- ART Scale changes [1 Day]
Absolute change, in number of points, on the ART scale between before and after injection to measure language-related symptoms.
- motor symptoms changes [1Day]
Absolute change, in number of points, on the Fugl-Meyer scale, between before and after injection to measure motor symptoms.
- Visual symptoms changes [1 Day]
Relative evolution, in percentage, of static perimetry score between before and after injection to measure visual symptoms.
- NIHSS score changes [1 Day]
Change in severity of neurological sequelae measured by the relative change in the National Institutes of Health Stroke Scale (NIHSS score) between before and after injection.
Eligibility Criteria
Criteria
Inclusion Criteria:
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Ischemic stroke more than 30 days old
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Age between 18 and 85 years old
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At least one deficit among:
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motor deficit: score < 56 on the Fugl-Meyer scale
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aphasia: score ≥4 on the Aphasia Rapid Test,
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presence of a clinically observable visual scotoma
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Having given their written consent
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Be affiliated with a social security scheme, Universal Medical Coverage (CMU) or any equivalent scheme
Exclusion Criteria:
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Hypersensitivity to amide-bonded local anesthetics.
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Atrioventricular conduction disorders requiring permanent electro-systolic training not yet performed.
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Epilepsy not controlled by treatment.
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Porphyritic subjects.
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Patients with a motor deficit (but no aphasia or scotomas) in whom there is spasticity leading to a major reduction in joint amplitude in passive motion
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Minor patients, under curatorship or guardianship, under legal protection, deprived of liberty, pregnant or breastfeeding women
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Pathologies involving the vital prognosis or compromising follow-up during the study period
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Patient undergoing local amine anesthesia in the 7 days preceding V1.
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Patients currently treated with no anti-arrhythmics such as tocainide, aprindine and mexiletine
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Patients with a contraindication to MRI (ferro-magnetic surgical clips, eye implants, metallic foreign body intraocular or in the nervous system, implants or metallic objects likely to contain the radiofrequency field, cochlear implants, cerebral or cardiac pacemaker , implantable cardiac defibrillators)
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Patients participating in research involving the therapeutic human person who may modify functional recovery (whether by medication or by medical device) or subject to an exclusion period for another research
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Hôpital Pitié Salpetrière | Paris | France | 75013 |
Sponsors and Collaborators
- Assistance Publique - Hôpitaux de Paris
Investigators
None specified.Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- APHP190723
- 2021-005507-13