Amyotrophic Lateral Sclerosis
Conditions
Interventions
Product Name: autologous adult bone marrow mononuclear cells (BM-MNC) unexpanded
Pharmaceutical Form: Solution for injection/infusion in pre-filled syringe
INN or Propo
Sponsors
Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
Eligibility
Sex/Gender
All
Inclusion 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 that offers sufficient guarantees of adherence to the protocol. - Neurophysiological data that confirm lower motor neuron involvement at lumbar and cervical level. - Assessment of the motor deficit in the dorsiflexion of both feet (between 3 and 5 points on the MRC scale). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 90 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: Mellitus diabetes. - Other diseases that may occur with polyneuropathies. - Previous history of cerebral stroke. - Previous pathology of the peripheral nervous system that affects one or both lower or upper limbs, with or without clinically evident neurological sequelae. - Pregnant or breast-feeding patients - Patients who are physiologically capable of becoming pregnant, unless they are using a reliable method of contraception (Annex III) - Patients with cardiac, renal, hepatic, systemic, immune disease that may influence the patient's survival during the trial. - Positive serology for hepatitis B, hepatitis C or HIV. - Clinical and anesthesiological criteria that contraindicate either sedation or the extraction of MO 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. - Inability to understand informed consent.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 1. To determine if the infusion of autologous intramuscular MON CMN in the tibialis anterior and 1st dorsal inteosseus muscles of patients with ALS can stop or slow down the progressive loss of functional motor units in these muscles. 2. To study, in a sufficient sample of patients with ALS, whether the different degree of involvement and the different evolution of the pathological process in different muscles, characteristic very typical of this disease, translates into an efficacy different from the intramuscular injection of CMN of MO. Clinical heterogeneity and the presence of muscles with different degrees of involvement will be completed with genetic studies 3. Determine the safety of the procedure. ; Secondary Objective: 1. To make a detailed study and a prolonged follow-up of the functional (electrophysiological) properties of the motor units of two upper and lower extemity muscles in ALS patients. Determine which electrophysiological parameters (fundamentally those related to the estimation of the number of functional motor units) correlate better with the evolution of the disease. 2. To determine the utility of muscle ultrasound for the monitoring of muscle morphology in the evolution of patients with ALS. 3. Carry out a genetic study of the patients included in the trial in order to correlate clinical aspects of the disease and the effect of the procedure with the presence of genetic alterations recently described and related to sporadic ALS (e.g. C9orf72). ; Primary end point(s): D50 index obtained from the stimulus intensity curves - size of the PAMC (D50, number without dimensions) Absence of AAG with possible, probable or defined relationship with the procedure. Rate of non-serious adverse events with possible, probable or defined relationship with the procedure. ; | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Neurophysiological: -Techniques for estimating the number of functional motor units (MUNE) by: 1. Quantification of the PAMC curve using the D50 index (no.). 2. "Motor unit number index (MUNIX and MUSIX) (number and microV respectively). - Density of fibers (DF): No. Quantifies the average number of muscle fibers per motor unit. It is obtained from records made with concentric needle electrodes. The average number of motor unit potentials is calculated at 20 different positions in the muscle. - Compound muscle action potential (PAMC) o Amplitude of the PAMC: mV o Area of ??the PAMC: mV / ms PAMC is recorded after stimulation with supramaximal intensity (pulses of 0.1-0.2 ms 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. In the TA PAMC it will be registered simultaneously in 5 positions oriented longitudinally along the TA muscle. To determine these 5 positions, bone references that are reproducible between members and between different patients will be used. From among the records obtained in these 5 positions, the one in which the amplitude and / or area of ??the PAMC is maximum will be selected and all the parameters obtained from the records in this position (MUNE and DF) will be used for the statistical analysis. This registration position will also be used as a reference for the infusion in the TA muscle of the autologous MON CMNs (experimental) or placebo (control). In the PID, the optimal point of registration will be determined, which will also be the reference for intramuscular injection. ;Timepoint(s) of evaluation of this end point: 24 months | — |
Countries
Spain
Contacts
Public ContactLola Serna Guirao
Fundación para la Formación e Investigación Sanitarias de la Región de Murcia
Outcome results
None listed