Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety of Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis by a prospective, single-center, randomized, parallel, double-blind, placebo-controlled phase I clinical trial.

Official Title
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Phase I Clinical Trial on Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis.

Conditions
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ALS (Amyotrophic Lateral Sclerosis)

Intervention / Treatment
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* Biological: MNC (Mononuclear cells)
* Other: Saline


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of definite or probable ALS according to the criteria established by the World Federation of Neurology Patient that provides reasonable assurance of adherence to protocol. Neurophysiological data confirming affectation of lower motor neurons in the lumbar region. Assessment of motor deficits in dorsiflexion of both feet (4 or 5 points on the MRC scale) The patient must fulfill all inclusion criteria. Exclusion Criteria: Diabetes Mellitus. Other diseases that may present with polyneuropathy. Previous history of stroke. Prior Pathology of the peripheral nervous system affecting one or both lower limbs with or without clinically evident neurological sequelae. Pregnant or breastfeeding patients active. Patients physiologically capable of becoming pregnant, unless they are using reliable contraception. Patients with cardiac disease, renal, hepatic, systemic, immune that may influence patient survival during the test. Positive serology for hepatitis B, hepatitis C or HIV. Clinical and anesthesiologic Criteria, contraindicating either sedation or extraction of MO (Altered coagulation system or anticoagulated patient with inability to withdraw anticoagulation, hemodynamic instability, altered skin puncture site, etc.) Included in other clinical trials in the last 6 months.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MNC (Mononuclear cells)<br>All patients included in the clinical trial will receive an intramuscular infusion of autologous mononuclear cells (MNC) of Bone Marrow (BM) in TA muscle of one of the lower limb (experimental group). The lower limb on the CMN infuse autologous BM will be determined randomly. The average dose is 550 millions of cells (100-1200 million) diluted in 2 ml. saline | Biological: MNC (Mononuclear cells)<br>* The cells are infused into the TA muscle of the lower limb randomized as Group A (experimental) intramuscularly. The infusion is made with a needle, 26 gauge, at 4 points of the TA muscle a specific depth given by the neurophysiological study. The total volume infused will be 2 ml, 0.5 ml at each point. For infusion is as painless as possible for the patient to comply exactly with stereotactic indications of neurophysiology, the infusion was made at a uniform controlled rate and for this, the syringe is placed on a Yesargil arm, equipped with a microinjector and controlled infusion device.<br>|
| Placebo Comparator: Saline<br>All patients included in the clinical trial will receive an intramuscular infusion of 2 mL of saline (placebo) in the TA muscle of the contralateral limb (group control). | Other: Saline<br>* The placebo, 2ml of saline, will be infused like in the experimental arm.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of serious and non-serious adverse events related to the use of bone marrow mononuclear cells in patients with Amyotrophic Lateral Sclerosis. |  | 24 months from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Estimated number of motor units (MUNE) | Several techniques for estimating the MUNE, all based on the relationship between the amplitude or area of compound muscle action potential (CMAP) and amplitude or area corresponding to a single motor unit response. The differences between the techniques are due to the different ways of estimating the amplitude of the responses for individual motor units. The study will use two techniques: Incremental Technique: The unitary amplitude (or area) of individual motor units are calculated from the responses to increasing intensities stimuli near of intensity threshold (Dantes and McComas, 1991) Statistical technique: The unit amplitude (or area) of the individual motor units are calculated from the amplitude variations (or area) of the muscle action potential obtained in response to stimuli from a fixed intensity (Daube, 2006) | 24 months from baseline | 
| Compound muscle action potential (CMAP) | CMAP is registered after supramaximal stimulation intensity (0.1-0.2 ms pulses at 1 Hz) of the common peroneal nerve at the level of the head of the fibula. The electrical stimulus is placed in a fixed position during the entire registration process. CMAP will be recorded simultaneously in 5 positions along longitudinally oriented TA muscle. To determine these 5 positions bony landmarks that are reproducible between members and between different patients will be used. | 24 months from baseline | 
| Fiber density (FD) | Quantifies the average number of muscle fibers per motor unit. It is obtained from single fiber recordings made with electrodes. The average number of motor unit potentials is calculated in 20 different positions in the muscle. | 24 months from baseline | 
| Muscle force MRC (Medical Research Council) score |  | 24 months from baseline | 
| Maximum force developed in an isometric contraction of the tibialis anterior (TA) muscle. | The measurement will be done in Newtons, with a dynamometer during dorsiflexion of the foot (from certain angles). | 24 months from baseline | 
| Maximum transversal area of the tibialis anterior (TA) | The area will be measured in cm2 by echography. | 24 months from baseline |