Biological Treatment of Amyotrophic Lateral Sclerosis

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to test the safety and effectiveness of an autologous bone marrow-derived stem/progenitor cells infusion in the subjects with diagnosed amyotrophic lateral sclerosis.

Detailed Description
-----------------
Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative condition that causes weakness leading to paralysis and death. Life expectancy is less that 5 years. The cause is generally unknown and there is no effective treatment. Patients with ALS typically exhibit a progressive paralysis due to the continued loss of motoneurons. Intraspinal injections of bone marrow mononuclear cells have been able to ameliorate the course of ALS in murine models. The purpose of this prospective, nonrandomized, open label, pilot study is to conduct the investigation of the safety and efficacy of infusion of autologous bone marrow-isolated stem/progenitor cells with different selected phenotypes into the subjects with diagnosed ALS. Especially, this clinical trial is designated to test the therapeutic (pro-regenerative and neuro-protective) functions of different stem/progenitor cell populations able to secrete bioactive neurotrophic factors. All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage of ALS with the duration of disease less than 6 months and patients diagnosed with advanced stage of ALS disease with duration of 6-12 months will be recruited and allocated based on their disease severity to two treatment groups: Group I - patients of early ALS disease stage and Group II - patients of advanced ALS disease. Next, autologous bone marrow-isolated stem/progenitor cells administration 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), functional rating scale (FRS) and maximum voluntary isometric contraction-arm (MVIC-arm) evaluation, to establish ALS progression rate will be recorded throughout the duration of the post-treatment follow up period.

Official Title
-----------------
Safety/Efficacy Study for the Biological Treatment of Amyotrophic Lateral Sclerosis With Autologous Stem/Progenitor Cells

Conditions
-----------------
Amyotrophic Lateral Sclerosis

Intervention / Treatment
-----------------
* Other: Biological: Cell-based therapeutics
* Other: Symptomatic treatment of ALS


Participation Criteria
=================
Eligibility Criteria
-----------------
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 patient is mentally intact and psychologically stable signed informed consent Exclusion Criteria: Concomitant of other systemic disease or diseases: inflammation (high protein or lymphocytosis in the CSF), active infections. diabetes, cardio-vascular disorders, cancer, autoimmune diseases renal failure, impaired hepatic function. subject is a respiratory dependent. subject unwilling or unable to comply with the requirements of the protocol. patient has been treated previously with any cellular therapy.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Stem/progenitor cells transplantation.<br>Intervention: Biological: Cell-based therapeutics Autologous bone marrow-derived stem/progenitor cells will be transplanted intrathecally (via a standard lumbar puncture) into early vs. progressive ALS subjects. | Other: Biological: Cell-based therapeutics<br>* Human autologous bone marrow-derived stem/progenitor cell transplantation in ALS patients.<br>|
| Sham Comparator: Standard treatment of ALS<br>Symptomatic treatment of ALS without biologic cell-based treatment | Other: Symptomatic treatment of ALS<br>* Symptomatic neurological treatment of ALS<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of autologous bone marrow stem/progenitor cell infusion in enrolled patients | Confirm the safety of autologous bone marrow stem/progenitor cell infusion in enrolled patients by repeated follow-up over one year with clinical and laboratory evaluations. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of autologous bone marrow stem/progenitor cell infusion in enrolled patients. | Confirm the efficacy of autologous bone marrow stem/progenitor cell infusion in enrolled patients by repeated follow-up over one year with clinical and laboratory evaluation tests for neurodegeneration processes analysis and general health outcomes. | 1 year | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
cell-based therapy, autologous bone marrow-derived stem/progenitor cells, stem cell infusion, stem cell transplantation, biological therapy with neurotrophic factors, bioactive neurotrophic factors