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

• Neurological variables: The Amyotrophic Lateral Sclerosis Functional Rating Scale (ALS-FRS), Medical Research Council (MRC) and Norris scales [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Absence of adverse events [ Time Frame: Every week / month depending on the study phase ] [ Designated as safety issue: Yes ]
• Neurophysiological variables: Electromyography, polysomnography, evoked potentials [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Neuroradiological variables: Spinal Magnetic Resonance Imaging (MRI) [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Respiratory variables: Maximal inspiratory pressure (PIM), Maximal expiratory pressure (PEM), sniff nasal, oxymetry. [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Psychological variables: Health Questionnaire (EuroQol-5D), The Profile of Mood States (POMS) [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]

• Neurological variables: ALS-FRS, MRC and Norris scales [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Absence of adverse events [ Time Frame: Every week / month depending on the study phase ] [ Designated as safety issue: Yes ]
• Neurophysiological variables: Electromyography, polysomnography, evoked potentials [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Neuroradiological variables: Spinal RMN [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Respiratory variables: PIM(VR), PEM (CPT), sniff nasal, PO2, PCO2, oxymetry [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
• Psychological variables: EuroQol-5D, POMS [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]

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.

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.

• Procedure: Laminectomy and bone marrow stem cells transplantation

  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

• Procedure: Intrathecal infusion of autologous bone marrow stem cells

  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.

• Procedure: Intrathecal infusion of placebo (saline solution).
  Patients were infused 2 ml of saline solution

• Experimental: Autologous bone marrow stem cells intraspinal transplantation
  T3-T4 laminectomy and bone marrow ficoll separated mononuclear autologous cells intraspinal transplantation
  Intervention: Procedure: Laminectomy and bone marrow stem cells transplantation
• Experimental: Intrathecal infusion of autologous bone marrow stem cells
  Patients were drawn 2 ml of cerebrospinal fluid and infused 2 ml (two 1 ml syringes) of Autologous Stem Cells.
  Intervention: Procedure: Intrathecal infusion of autologous bone marrow stem cells
• Placebo Comparator: Intrathecal infusion of placebo (saline solution).
  Patients were infused 2 ml of saline solution
  Intervention: Procedure: Intrathecal infusion of placebo (saline solution).

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

• Instituto de Salud Carlos III
• Hospital Universitario Virgen de la Arrixaca
• Hospital General Universitario Morales Meseguer
• Fundación Diógenes