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

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

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.

Study Overview

• Status: Completed
• 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).

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.

• Study Type: Interventional
• Enrollment (Actual): 63
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Murcia
    • El Palmar, Murcia, Spain
      • Hospital Universitario Virgen de La Arrixaca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Autologous bone marrow stem cells intraspinal transplantation; T3-T4 laminectomy and bone marrow ficoll separated mononuclear autologous cells intraspinal transplantation	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
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.	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.
Placebo Comparator: Intrathecal infusion of placebo (saline solution).; Patients were infused 2 ml of saline solution	Procedure: Intrathecal infusion of placebo (saline solution).; Patients were infused 2 ml of saline solution

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Forced vital capacity	Every 3 months

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
• Collaborators: Instituto de Salud Carlos III; Hospital Universitario Virgen de la Arrixaca; Hospital General Universitario Morales Meseguer; Diógenes Foundation
• Investigators: Study Director: Jose María Moraleda Jiménez, M.D. PhD., Hospital Universitario Virgen de La Arrixaca

Publications and helpful links

Helpful Links

• Spanish Cell Therapy Network
• Amyotrophic Lateral Sclerosis

Study record dates

Study Major Dates

• Study Start: October 1, 2010
• Primary Completion (Actual): November 20, 2015
• Study Completion (Actual): November 20, 2015

Study Registration Dates

• First Submitted: December 3, 2010
• First Submitted That Met QC Criteria: December 3, 2010
• First Posted (Estimate): December 6, 2010

Study Record Updates

• Last Update Posted (Actual): March 30, 2017
• Last Update Submitted That Met QC Criteria: March 29, 2017
• Last Verified: November 1, 2015

More Information

Terms related to this study

• Keywords: Safety; Amyotrophic Lateral Sclerosis; Stem cells; Autologous; Bone marrow
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: Extension CMN/ELA; 2006-003096-12 (EudraCT Number); EC07/90762 (Other Identifier: ISCIII)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No