Clinical Trial in Phase II of Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis.
Overview
- Phase
- Phase 2
- Intervention
- MNC (Mononuclear cells)
- Conditions
- ALS (Amyotrophic Lateral Sclerosis)
- Sponsor
- Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia
- Enrollment
- 100
- Locations
- 1
- Primary Endpoint
- D50 index obtained from stimulus intensity curves
- Last Updated
- 5 years ago
Overview
Brief Summary
Our working hypothesis is that the injection of autologous bone marrow mononuclear cells (BMNC) has a positive effect on the natural loss of motor units and on the increase in the size of the motor unit that occurs in patients with ALS during the evolution of the disease
Detailed Description
Our working hypothesis is that the injection of autologous bone marrow mononuclear cells (BMNC) has a positive effect on the natural loss of motor units and on the increase in the size of the motor unit that occurs in patients with ALS during the evolution of the disease. This hypothesis is based on experimental work done in animal models of ALS and the results of our previous phase I clinical trial. In this clinical trial (TCIM / ALS, ClinicalTrials.gov Identifier: NCT02286011) we studied with electrophysiological techniques (in a small number of patients with ALS) the effects of intramuscular injection of a single dose of BMSC in the tibialis anterioris (TA) muscle. . The results indicate that this is a safe procedure and show the presence of a positive and apparently transitory effect on the size and number of motor units of the TA muscle.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Diagnosis of ALS defined or probable according to the criteria established by the World Federation of Neurology
- •Age between 18 and 70 years.
- •Patient who offers sufficient guarantees of adherence to the protocol.
- •Neurophysiological data confirming lower motor neuron involvement at the lumbar and cervical level.
- •Assessment of the motor deficit in the dorsal flexion of both feet (between 3 and 5 points on the MRC scale).
Exclusion Criteria
- •Mellitus diabetes.
- •Other diseases that may be associated with polyneuropathies.
- •Previous history of cerebral stroke.
- •Previous pathology of the peripheral nervous system that affected one or both lower or upper limbs, with or without clinically evident neurological sequelae.
- •Pregnant or actively breastfeeding patients
- •Patients physiologically capable of becoming pregnant, unless they are using a reliable contraceptive method (Annex III)
- •Patients with cardiac, renal, hepatic, systemic, immune disease that may influence the survival of the patient during the test.
- •Positive serology for hepatitis B, hepatitis C or HIV.
- •Clinical and anesthesiological criteria that contraindicate either sedation or the extraction of BM itself (Alteration of the coagulation system or anticoagulated patient with inability to withdraw anticoagulation, hemodynamic instability, skin alteration in the puncture site, etc.)
- •Inclusion in other clinical trials in the last 6 months.
Arms & Interventions
MNC (Mononuclear cells)
MNC (Mononuclear cells) (patients in which stem cells will be injected into the two muscles on one side and placebo -vehicle- in the two contralateral muscles). This group would consist of 74 patients.
Intervention: MNC (Mononuclear cells)
MNC (Mononuclear cells)
MNC (Mononuclear cells) (patients in which stem cells will be injected into the two muscles on one side and placebo -vehicle- in the two contralateral muscles). This group would consist of 74 patients.
Intervention: Placebo / Saline
Saline
(patients in which placebo -vehicle- will be injected into both muscles on both sides). This group would consist of 26 patients.
Intervention: Placebo / Saline
Outcomes
Primary Outcomes
D50 index obtained from stimulus intensity curves
Time Frame: 48 months from baseline
This parameter quantifies the number and size of the functional motor units of a given muscle.
Rate of serious and non-serious adverse events related to the use of bone marrow mononuclear cells in patients with Amyotrophic Lateral Sclerosis
Time Frame: 48 months from baseline
Secondary Outcomes
- Fiber density (FD)(48 months from baseline)
- Maximum force developed in an isometric contraction of the muscles(48 months from baseline)
- Fuerza muscular (MRC Medical Research Council) score(48 months from baseline)
- Motor unit number index" (MUNIX)(48 months from baseline)
- PAMC area: mV / ms(48 months from baseline)
- Motor unit size index" (MUSIX)(48 months from baseline)
- PAMC amplitude: mV(48 months from baseline)