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

Sponsor

Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud (Other)

Overall Status

Completed

CT.gov ID

NCT02290886

Collaborator

Iniciativa Andaluza en Terapias Avanzadas (Other)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Amyotrophic Lateral Sclerosis	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	Phase 1/Phase 2

Detailed Description

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

Randomized

Intervention Model:

Single Group Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jul 1, 2014

Actual Primary Completion Date :

Mar 2, 2022

Actual Study Completion Date :

Mar 2, 2022

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Placebo Intravenous administration of placebo	Other: Intravenous administration of placebo
Experimental: 1 million of MSC Intravenous administration of 1 million of MSC/ kg	Drug: Intravenous administration of 1 million of MSC
Experimental: 2 million of MSC Intravenous administration of 2 million of MSC/ kg	Drug: Intravenous administration of 2 million of MSC
Experimental: 4 million of MSC Intravenous administration of 4 million of MSC/ kg	Drug: Intravenous administration of 4 million of MSC

Outcome Measures

Primary Outcome Measures

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)
Complications in the place of the infusion [6 months]
To evaluate the safety of the intravenous administration of 3 doses of autologous
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

Secondary Outcome Measures

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Hospital Regional Universitario Reina Sofía	Cordoba	Spain	14004
2	Hospital Regional Universitario de Málaga	Málaga	Spain	29010
3	Hospital Universitario Virgen Macarena, Servicio de Neurología	Seville	Spain	41009
4	Hospital Universitario Virgen del Rocío	Seville	Spain	41013