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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-004801-25 | EudraCT Number |
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| Name | Class |
|---|---|
| Spanish National Health System | OTHER |
| Hospital Universitario Virgen de la Arrixaca | OTHER |
| Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| MNC (Mononuclear cells) | Experimental | 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 |
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| Saline | Placebo Comparator | 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). |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| MNC (Mononuclear cells) | Biological | 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. |
| 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 |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| JoaquÃn A Gómez Espuch, MD | Hospital Universitario Virgen de la Arrixaca | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Universitary Hospital Virgen de la Arrixaca | El Palmar | Murcia | 30120 | Spain |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22415951 | Result | Blanquer M, Moraleda JM, Iniesta F, Gomez-Espuch J, Meca-Lallana J, Villaverde R, Perez-Espejo MA, Ruiz-Lopez FJ, Garcia Santos JM, Bleda P, Izura V, Saez M, De Mingo P, Vivancos L, Carles R, Jimenez J, Hernandez J, Guardiola J, Del Rio ST, Antunez C, De la Rosa P, Majado MJ, Sanchez-Salinas A, Lopez J, Martinez-Lage JF, Martinez S. Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study. Stem Cells. 2012 Jun;30(6):1277-85. doi: 10.1002/stem.1080. | |
| 32265627 |
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| ID | Term |
|---|---|
| D000690 | Amyotrophic Lateral Sclerosis |
| ID | Term |
|---|---|
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D016472 | Motor Neuron Disease |
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| ID | Term |
|---|---|
| D012965 | Sodium Chloride |
| ID | Term |
|---|---|
| D002712 | Chlorides |
| D006851 | Hydrochloric Acid |
| D017606 | Chlorine Compounds |
| D007287 | Inorganic Chemicals |
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| Public Health Service, Murcia |
| OTHER |
| Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca | OTHER |
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| Saline | Other | The placebo, 2ml of saline, will be infused like in the experimental arm. |
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| 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 |
| Derived |
| Geijo-Barrientos E, Pastore-Olmedo C, De Mingo P, Blanquer M, Gomez Espuch J, Iniesta F, Iniesta NG, Garcia-Hernandez A, Martin-Estefania C, Barrios L, Moraleda JM, Martinez S. Intramuscular Injection of Bone Marrow Stem Cells in Amyotrophic Lateral Sclerosis Patients: A Randomized Clinical Trial. Front Neurosci. 2020 Mar 24;14:195. doi: 10.3389/fnins.2020.00195. eCollection 2020. |
| D019636 | Neurodegenerative Diseases |
| D057177 | TDP-43 Proteinopathies |
| D009468 | Neuromuscular Diseases |
| D057165 | Proteostasis Deficiencies |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D017670 |
| Sodium Compounds |