A Multicenter Phase I/II Clinical Trial to Evaluate Safety of Mesenchymal Stem Cell in Patients With Amyotrophic Sclerosis Lateral

Study Overview
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Brief Summary
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A multicenter phase I/II Clinical trial,randomized, controlled with placebo, triple blind to evaluate the safety of the intravenous administration of 3 doses of autologous mesenchymal stem cells cells from adipose tissue in patients with Amyotrophic Lateral Sclerosis (ALS).

Detailed Description
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A multicenter phase I/II Clinical trial,randomized, controlled with placebo, triple blind to evaluate the safety of the intravenous administration of 3 doses of autologous mesenchymal stem cells cells from adipose tissue in patients with Amyotrophic Lateral Sclerosis (ALS). 40 patients will be enrolled and will be randomized into one of the following 4 arms: 10 patients in the control group (placebo) 10 patients received a dose of 1 million MSC / kg 10 patients received a dose of 2 million MSC / kg. 10 patients received a dose of 4 million MSC / kg The follow-up phase of each patient from the cell infusion/placebo will be 6 months. At the time that each patient completed the follow-up period (i.e., 6 months after the infusion of the cellular product or placebo), the blind will be open, and patients who have been assigned to the control group, will receive the cell product as secondary treatment. These patients will be randomized to receive each of the doses used in the first phase. From this point, they begin a second period of follow up of 6 months. In addition, after 6 months of MSC infusion, every patient will continue in an open extension study for 36 months to assess the safety of MSC.

Official Title
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A Multicenter Phase I/II Clinical Trial, Randomized, Controlled With Placebo, Triple Blind to Evaluate Safety, and Indications of Efficiency of the Intravenous Administration of the Therapy With 3 Doses of MSC in Patients With ASL Moderated to Severe

Conditions
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Amyotrophic Lateral Sclerosis

Intervention / Treatment
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* Other: Intravenous administration of placebo
* Drug: Intravenous administration of 1 million of MSC
* Drug: Intravenous administration of 2 million of MSC
* Drug: Intravenous administration of 4 million of MSC


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Women and males over 18-year-old. Good understanding of the protocol and aptitude to grant the informed assent. Diagnosis of sporadic ALS, with diagnosis of certainty, that is to say, definite or probable, in agreement with the criteria of El Escorial, of the World Federation of Neurology. Forced vital capacity of at least 50 % of the one that would correspond to them for sex, height and age. More than 6 and less than 36 months of evolution of the disease (from the beginning of the symptoms). Possibility of obtaining, at least, 50gr of adipose tissue. Treatment with riluzole, for at least, a month before the inclusion. Exclusion Criteria: Any concomitant disease that under investigator's criteria could concern the measures of the clinical variables of the trial (hepatic, renal or cardiac insufficiency, diabetes mellitus, etc). Previous therapy with stem cells. Participation in another clinical trial during 3 months previous to the entry in this trial. Any disease lymphoproliferative Tracheostomy and /or gastrostomy. Haemophilia, diathesis hemorrhagic or anticoagulative current therapy. Hypersensitivity known to the bovine foetal whey or the gentamicin. Medical precedents of infection of the HIV or any serious condition of immunocompromised. Positive HBV or HCV serology Levels of creatinine in whey > 3.0 in subjects not submitted to haemodialysis.

Ages Eligible for Study
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Minimum Age: 18 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: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Intravenous administration of placebo | Other: Intravenous administration of placebo<br> <br> |
| Experimental: 1 million of MSC<br>Intravenous administration of 1 million of MSC/ kg | Drug: Intravenous administration of 1 million of MSC<br> <br> |
| Experimental: 2 million of MSC<br>Intravenous administration of 2 million of MSC/ kg | Drug: Intravenous administration of 2 million of MSC<br> <br> |
| Experimental: 4 million of MSC<br>Intravenous administration of 4 million of MSC/ kg | Drug: Intravenous administration of 4 million of MSC<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of adverse serious unexpected reactions or not, attributable to the treatment (SUSSARs or SAE) | To evaluate the safety of the intravenous administration of 3 doses of autologous mesenchymal stem cells (MSC) from adipose tissue in patients with Amyotrophic lateral Sclerosis (ALS) ABSENCE of: complications in the place of the infusion, appearance of a new neurological effect not attributable to the natural progression of this pathology and adverse serious unexpected reactions or not, attributable to the treatment (SUSSARs or SAE) | 6 months | 
| Complications in the place of the infusion | To evaluate the safety of the intravenous administration of 3 doses of autologous | 6 months | 
| Appearance of a new neurological effect not attributable to the natural progression of this pathology | To evaluate the safety of the intravenous administration of 3 doses of autologous | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in the progression of the disease (modifications in the scale of functionality of the ALS) |  | 6 months | 
| Changes in the degree of muscular force |  | 6 months | 
| Changes in the vital forced capacity |  | 6 months | 
| Changes of the muscular mass estimated by Nuclear Magnetic Resonance (NMR) of the upper and low extremities |  | 6 months | 
| Changes in neurophysiological parameters and of quality of life |  | 6 months | 
| Need and time to tracheotomy or permanent assisted ventilation |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ALS, safety evaluation, intravenous administration, 3 doses of autologous MSC