Autologous Bone Marrow Mesenchymal Stem Cells in the Treatment of Patients With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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The goal of this study is to investigate the safety and tolerability of autologous bone marrow-derived mesenchymal stem cells administration in the individuals with diagnosed amyotrophic lateral sclerosis.

Detailed Description
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Amyotrophic lateral sclerosis (ALS) is one of the progressive neurodegenerative disorders, affecting upper and lower motor neurons in the cerebral cortex, brainstem and spinal cord. Hence, the signs of damage motor neurons are both at the peripheral (eg. atrophy), and central (eg. spasticity) level. There is no effective treatment for ALS and the majority of patients die within 5 years after diagnosis, usually due to respiratory failure. Numerous studies on murine models revealed that mesenchymal stem cells (MSCs) successfully improve the clinical and pathological features of ALS. The goal of this nonrandomized, open label study is to investigate the safety and tolerability of autologous bone marrow-derived mesenchymal stem cell transplantation into the individuals with diagnosed amyotrophic lateral sclerosis. This clinical trial is conducted to test the therapeutic (neuroprotective and paracrine) effect of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients are recruited for a clinical trial not longer than 1 year from disease diagnosis. Then, patients are divided into two groups: Group I - patients receiving intrathecally one application of BM-MSCs and Group II - patients receiving intrathecally three applications (each administration every two months) of BM-MSCs. Subsequently, autologous bone marrow-derived mesenchymal stem cell transplantation to the cerebrospinal fluid at the site of the spinal cord will be performed. Finally, treatment safety, adverse events and exploratory parameters, including electromyographic (EMG) studies, forced vital capacity (FVC) and functional rating scale (FRS) to establish ALS progression rate will be recorded throughout the duration and in the post-treatment follow up period.

Official Title
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Evaluation of Mesenchymal Stem Cell Culturing Protocols in the Treatment of Amyotrophic Lateral Sclerosis

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Other: Biological: Cell-based therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosis of the ALS disease before the cell transplantation (diagnose established following the El Escorial criteria for definite ALS) good understanding of the protocol and willingness to consent signed informed consent disease duration: up to 2 years FVC > 50% / pulmonologist certificate about respiratory function of the patient Exclusion Criteria: cancer, autoimmune diseases renal failure, subject is a respiratory dependent. subject unwilling or unable to comply with the requirements of the protocol pregnancy, breastfeeding

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous BM-MSCs injection<br>Intervention: Biological: Cell-based therapy of autologous bone marrow-derived mesenchymal stem cells which are transplanted intrathecally (via a standard lumbar puncture) into the ALS subjects. | Other: Biological: Cell-based therapy<br>* Human autologous bone marrow-derived mesenchymal stem cell transplantation in ALS patients.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS) between patients before and after stem cell transplantation. | ALSFRS is ordinal rating scale questionnaire (rating 0-4 for each question, 4 is most functional, 0-48 total) of 12 functional activities. The most functional total score is 48. The First time the ALSFRS questionnaire has been dane after enrolment of the patients and then after 6 months of observation and stem cell injections the ALSFRS has been dane every 2 months up to 1,5 year of follow-up period. | From day of enrolment until the date of first stem cell injection (6 months - first time ALSFRS) + and then every 2 months up to 1,5 year of the trial |