Human Neural Stem Cell Transplantation in Amyotrophic Lateral Sclerosis (ALS)

Study Overview
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Brief Summary
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Primary aim of the trial to verify safety and tolerability of expanded human fetal neural stem cells to verify safety and tolerability of a microsurgery human fetal neural stem cells transplantation model to recognize each change in patient's quality of life Secondary aim of the trial assessment of the impact of human neural stem cells transplantation on the disability of ALS in a clinically significant and measurable way Assessment of the impact of human neural stem cells transplantation on mortality (all causes)

Detailed Description
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18 patients diagnosed as definite ALS according to the El Escorial criteria will be recruited during two years. The patients will be divided into 3 groups with different severity. Each group will be less compromised than the group that went before them. Their breathing measurements must be at least 60%. Subjects will receive injections of the human foetal neural stem cells into the spinal cord. A variety of tests and examinations will take place every month for the first year and every three months for the next two in order to monitor the course of the disease and the adverse events.

Official Title
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Intra-spinal Cord Delivery of Human Neural Stem Cells in ALS Patients: Proposal for a Phase I Study/ Trapianto Intramidollare di Cellule Staminali Neurali Umane Come Terapia Putativa Per la SLA: Proposta di un Trial Clinico di Fase I

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Biological: Human Neural Stem Cells


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of definite or possible ALS according to revised EL Escorial criteria Age: 20-75 years documented progression of disease during the last 6 months. Absence of concomitant diseases Adequate assurances of adherence to protocol The patient must be able to communicate verbally or with the use of non-verbal communication system Group 1 maximum score of 1 on walking item of ALS functional rating scale forced vital capacity > or equal to 60 Group 2 forced vital capacity > or equal to 60 ambulation difficulties (maximum score of 2 on walking item of ALS functional rating scale) Group 3 Independent ambulation (score 4 on a scale ALS-FRS) forced vital capacity > or equal to 70 Exclusion Criteria: The presence of at least one of the following will lead to patient exclusion. psychiatric diseases or other neurological diseases different from ALS other systemic diseases Neoplasms or other diseases reducing life expectancy Antecedent polio infection corticosteroids, immunoglobulin or immunosuppressive treatment involvement in other clinical trials 2 or more critical items in MMPI neuropsychological evaluation suggestive of mental deterioration or cognitive sphere disturbance. Impediments to MRI patients unable to understand informed consent form and study aims. women who are pregnant or childbearing potential for the duration of the study. Non-pregnant status will be documented by beta-HCG negative test 7 days before treatment start

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 75 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

Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Human Neural Stem Cells Suspension<br>50,000 cells/µl. Patients received either unilateral or bilateral hNSCs microinjections (3 microinjections on each side) into the lumbar spinal cord. Each microinjection consisted of 15 µl of the above 50,000cells/µl suspension, yielding a total of 750,000 cells per injection site. | Biological: Human Neural Stem Cells<br>* Surgical microinjection of human neural stem cells on spinal cord of ALS patients<br>* Other names: Human Neural Stem Cells Suspension;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety of a microsurgery human neural stem cells transplantation into spinal cord of ALS patients | Percentage of subjects (%) with treatment-related mortality defined as death due to procedure and not to the course of the disease Number of adverse events related to the procedure Changes in neuroradiological (MRI) and neurophysiological variables (SEP, MEP) Changes in neuropsychological variables | Participants will be followed for at least 3 years. Monthly in the first year and every three months the following two years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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amyotrophic lateral sclerosis, motor neuron disease, stem cells, safety, ALS-FRS-Functional scale R and FVC (%) variation, Survival analysis, Changes in quality of life scales