Clinical trial NCT04488965: Study of the Therapeutic Effects of Cortical Autograft Implantation in Patients With Cerebral Ischemia
Official title: Study of the Therapeutic Effects of Cortical Autograft Implantation in Patients With Cerebral Ischemia
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Ischemic Stroke
Keywords: autologous transplant
brain cell therapy
motor cortex lesion
cortical autograft
Lead sponsor: Centre Hospitalier Universitaire Vaudois
Sponsor class: OTHER
First posted: 2020-07-28
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: monocentric, non-randomized, open-label with single-arm design
Primary purpose: TREATMENT

Brief summary: Brain lesions in the adult have dramatic consequences, because the spontaneous capacity of the brain to functionally recover is limited. Besides existing rehabilitative therapeutic approaches (e.g. physiotherapy), several lines of research aim at developing treatments to promote and refine brain plasticity to enhance functional recovery following brain injury.

This pilot clinical study aims at enrolling subjects victim of a stroke with neuronal destruction leading to a disabling motor deficit. Usually these patients benefit from intensive neurorehabilitation which allows them to progress up to a certain point but when their recovery plateau is reached; current medicine is disarmed and no effective treatment allows, to date, to improve further their performance. This monocentric pilot study aims at evaluating the feasibility and safety of Autologous Neural Cell Ecosystems (ANCE), which is a cortical autograft intended to be used on stroke patients, for the replacement of motor neurons destroyed during an ischemic stroke.

Detailed description: Using neural grafts to restore function after lesions of the central nervous system is a challenging strategy. Most of the transplantation experience acquired the last decades was focused on fetal neuronal grafts. However, despite the great enthusiasm generated by this approach, ethical controversies, immune rejection, and lack of fetal donors remain a major problem. Therefore, autotransplantation of adult brain cells represents an attractive restoration alternative to bypass the caveats of fetal grafting.

The optimization of the procedure to obtain ANCE, a cortical autograft obtained from cortical biopsy, was first successfully demonstrated in producing long-term primary culture of adult human brain cells from temporal lobe tissues obtained from epilepsy and trauma neurosurgical patients. ANCE has been characterized as an ecosystem of autologous neural cells in suspension, composed of several cell types: astrocytes, proliferative progenitors and quiescent progenitors.

The production of ANCE has been implemented to prepare long-term primary culture from primate cortical biopsies. This allowed assessing the feasibility of autotransplantation from brain biopsy to reimplantation of cultured brain cells in a non-human primate model of motor cortex lesion. On the same model of cerebral cortex lesion in nonhuman primates, further study demonstrated, by quantitative behavioral evidence, the beneficial outcome of cell therapy following injury of the cerebral cortex.

Based on the encouraging results from past experiences on non-human primate model of motor cortex lesion, this monocentric pilot study aims at evaluating the feasibility and safety of ANCE (Autologous Neural Cell Ecosystems), which is cortical autograft intended to be used on stroke patients, for the replacement of motor neurons destroyed during an ischemic stroke.

Eligibility criteria: Inclusion Criteria:

* Be between 18 and 75 years old.
* Victim of a first ischemic stroke in superficial Sylvian territory with at least frontal damage.
* Cerebral ischemic lesion demonstrated by MRI.
* Stroke older than one year.
* Presence of a motor hemi-syndrome with at least one involvement of the upper limb.
* Stable neurological deficit in motor function of the limb greater than two months apart before enrolling the patient in the study.
* Woman of childbearing potential with a negative blood pregnancy test before the biopsy and using a reliable method of contraception during the study.
* Patient capable of discernment and of giving informed consent himself.
* Absence of other serious pathologies or comorbidities.

Exclusion Criteria:

* Brain lesions or a history of stroke or brain hemorrhage.
* Signs of peripheral neurological damage, such as radicular or trunk involvement
* History of spinal cord problems.
* History of neurosurgical intervention in the brain.
* surgical intervention contraindications.
* Anticoagulation, if it cannot be interrupted one week before and one week after each of the 2 brain surgeries.
* Coagulation disorders.
* Treatment of botulinum toxin during the last 3 months before inclusion.
* Seizures or anti-epileptic treatment.
* Global cognitive disorders, such as degenerative or vascular dementia.
* High blood pressure difficult to control.
* Alcohol or drug abuse.
* Known neoplasia.
* Inability to understand or cooperate in the study.
* MRI contraindication
* Pregnancy
* Penicillin intolerance or allergy

Primary outcomes:
measure: Assess the feasibility and safety of ANCE treatment by evaluating the incidence of treatment-related adverse events
timeFrame: 54 months (Visits will be carried out 2 years and 4 years after reimplantation in order to ensure that there is no long-term complication of ANCE reimplantation)
Secondary outcomes:
measure: Change in the medium term of the participant score when assessing the "Catherine Bergego Scale" (CBS)
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the participant score when assessing the NIHSS
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the participant score when assessing the Modified Rankin Scale
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the patient score when assessing the Action Research Arm Test (ARAT)
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the patient score when assessing the Box and Block Test (BBT)
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the patient score when assessing the Resistance to passive movement scale (Repas)
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the patient score when assessing Activities of Daily Living (ADL)
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the patient score when assessing Rivermead Mobility Index
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the patient score when assessing Berg Balance Scale
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
measure: Change in the medium term of the patient score when assessing London Handicap Scale (LHS)
timeFrame: up to 54 months (Assessment is performed at each visit up to the last visit 4 years after reimplantation)
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Centre Hospitalier Universitaire Vaudois
state: Canton De Vaud
Study officials:
References: