Clinical Trial on The Use of Autologous Bone Marrow Stem Cells in Amyotrophic Lateral Sclerosis (Extension CMN/ELA)

Study Overview
=================
Brief Summary
-----------------
The purpose of this clinical trial is to assess the feasibility and the security of the intraspinal and intrathecal infusion of autologous bone marrow stem cells for the treatment of Amyotrophic Lateral Sclerosis patients.

Detailed Description
-----------------
Patients with Amyotrophic Lateral Sclerosis (ALS) typically endure a progressive paralysis due to the continued loss of motoneurons that leads them to death in less than 5 years. No treatment has changed its natural history. Intraspinal injections of bone marrow mononuclear cells (MNC) have been able to ameliorate the course of ALS in murine models, acting as pumps of trophic factors that keep the motoneurons functional. Moreover, the clinical trial (Study NCT00855400 on www.ClinicalTrials.gov) conducted by our research group to determine the safety and efficacy of Autologous Stem Cell transplantation in Amyotrophic Lateral Sclerosis in humans, found that this procedure is feasible and safe. Continuing with that study, we have designed a phase I/II clinical trial to check the feasibility of the intraspinal and intrathecal infusion of autologous bone marrow stem cells.

Official Title
-----------------
Phase I/II Clinical Trial on The Use of Autologous Bone Marrow Stem Cells in Amyotrophic Lateral Sclerosis (Extension CMN/ELA)

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

Intervention / Treatment
-----------------
* Procedure: Laminectomy and bone marrow stem cells transplantation
* Procedure: Intrathecal infusion of autologous bone marrow stem cells
* Procedure: Intrathecal infusion of placebo (saline solution).


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnose established following the World Federation of Neurology criteria More than 6 and less than 36 months of evolution of the disease Medullar onset of the disease More than 18 and less than 70 years old Forced Vital Capacity ≥ 50% Total time of oxygen saturation <90% inferior to 5% of the sleeping time Signed informed consent Exclusion Criteria: Neurological or psychiatric concomitant disease Need of parenteral or enteral nutrition through percutaneous endoscopic gastrostomy or nasogastric tube Concomitant systemic disease Treatment with corticosteroids, immunoglobulins or immunosuppressors during the last 12 months Inclusion in other clinical trials Unability to understand the informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

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

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

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

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Autologous bone marrow stem cells intraspinal transplantation<br>T3-T4 laminectomy and bone marrow ficoll separated mononuclear autologous cells intraspinal transplantation | Procedure: Laminectomy and bone marrow stem cells transplantation<br>* Autologous bone marrow cells collection under sedation. Sixty ml are obtained and processed through a ficoll gradient. T3-T4 laminectomy and bone marrow ficoll separated mononuclear autologous cells intraspinal transplantation<br>|
| Experimental: Intrathecal infusion of autologous bone marrow stem cells<br>Patients were drawn 2 ml of cerebrospinal fluid and infused 2 ml (two 1 ml syringes) of Autologous Stem Cells. | Procedure: Intrathecal infusion of autologous bone marrow stem cells<br>* Autologous bone marrow cells collection under sedation. Sixty ml are obtained and processed through a ficoll gradient. Patients were drawn 2 ml of cerebrospinal fluid and infused 2 ml (two 1 ml syringes) of Autologous Stem Cells.<br>|
| Placebo Comparator: Intrathecal infusion of placebo (saline solution).<br>Patients were infused 2 ml of saline solution | Procedure: Intrathecal infusion of placebo (saline solution).<br>* Patients were infused 2 ml of saline solution<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Forced vital capacity |  | Every 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neurological variables: The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS-FRS), Medical Research Council (MRC) and Norris scales |  | Every 3 months | 
| Absence of adverse events |  | Every week / month depending on the study phase | 
| Neurophysiological variables: Electromyography, polysomnography, evoked potentials |  | Every 3 months | 
| Neuroradiological variables: Spinal Magnetic Resonance Imaging (MRI) |  | Every 3 months | 
| Respiratory variables: Maximal inspiratory pressure (PIM), Maximal expiratory pressure (PEM), sniff nasal, oxymetry. |  | Every 3 months | 
| Psychological variables: Health Questionnaire (EuroQol-5D), The Profile of Mood States (POMS) |  | Every 3 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Amyotrophic Lateral Sclerosis, Bone marrow, Stem cells, Autologous, Safety