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

Phase 1

Completed

Interventions: Other: Intravenous administration of placebo
Drug: Intravenous administration of 1 million of MSC
Drug: Intravenous administration of 4 million of MSC
Drug: Intravenous administration of 2 million of MSC

Lead Sponsor: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud

Brief Summary: 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: 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.

Recruitment & Eligibility

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.

Arm && Interventions

Group	Intervention	Description
Placebo	Intravenous administration of placebo	Intravenous administration of placebo
1 million of MSC	Intravenous administration of 1 million of MSC	Intravenous administration of 1 million of MSC/ kg
4 million of MSC	Intravenous administration of 4 million of MSC	Intravenous administration of 4 million of MSC/ kg
2 million of MSC	Intravenous administration of 2 million of MSC	Intravenous administration of 2 million of MSC/ kg

Primary Outcome Measures

Name	Time	Method
Number of adverse serious unexpected reactions or not, attributable to the treatment (SUSSARs or SAE)	6 months	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)
Appearance of a new neurological effect not attributable to the natural progression of this pathology	6 months	To evaluate the safety of the intravenous administration of 3 doses of autologous
Complications in the place of the infusion	6 months	To evaluate the safety of the intravenous administration of 3 doses of autologous

Secondary Outcome Measures

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

Locations (4): Hospital Regional Universitario Reina Sofía
🇪🇸
Cordoba, Spain
Hospital Regional Universitario de Málaga
🇪🇸
Málaga, Spain
Hospital Universitario Virgen Macarena, Servicio de Neurología
🇪🇸
Seville, Spain
Hospital Universitario Virgen del Rocío
🇪🇸
Seville, Spain