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

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

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).

Study Overview

• Status: Completed
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: 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

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.

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Spain
  • Cordoba, Spain, 14004
    • Hospital Regional Universitario Reina Sofía
  • Málaga, Spain, 29010
    • Hospital Regional Universitario de Malaga
  • Seville, Spain, 41013
    • Hospital Universitario Virgen del Rocio
  • Seville, Spain, 41009
    • Hospital Universitario Virgen Macarena, Servicio de Neurología

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Women and males over 18-year-old.
2. Good understanding of the protocol and aptitude to grant the informed assent.
3. 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.
4. Forced vital capacity of at least 50 % of the one that would correspond to them for sex, height and age.
5. More than 6 and less than 36 months of evolution of the disease (from the beginning of the symptoms).
6. Possibility of obtaining, at least, 50gr of adipose tissue.
7. Treatment with riluzole, for at least, a month before the inclusion.

Exclusion Criteria:

1. 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).
2. Previous therapy with stem cells.
3. Participation in another clinical trial during 3 months previous to the entry in this trial.
4. Any disease lymphoproliferative
5. Tracheostomy and /or gastrostomy.
6. Haemophilia, diathesis hemorrhagic or anticoagulative current therapy.
7. Hypersensitivity known to the bovine foetal whey or the gentamicin.
8. Medical precedents of infection of the HIV or any serious condition of immunocompromised.
9. Positive HBV or HCV serology
10. Levels of creatinine in whey > 3.0 in subjects not submitted to haemodialysis.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: Triple

Number of Arms

4

Arms and Interventions

Participant Group / 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

What is the study measuring?

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	Time Frame
Need and time to tracheotomy or permanent assisted ventilation	6 months
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

Collaborators and Investigators

• Sponsor: Andalusian Initiative for Advanced Therapies - Fundación Pública Andaluza Progreso y Salud
• Collaborators: Iniciativa Andaluza en Terapias Avanzadas
• Investigators: Study Chair: Óscar Fernández, MD, Hospital Regional U. de Málaga

Publications and helpful links

General Publications

• Ilieva H, Maragakis NJ. Motoneuron Disease: Clinical. Adv Neurobiol. 2017;15:191-210. doi: 10.1007/978-3-319-57193-5_7.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2014
• Primary Completion (Actual): March 2, 2022
• Study Completion (Actual): March 2, 2022

Study Registration Dates

• First Submitted: October 9, 2014
• First Submitted That Met QC Criteria: November 11, 2014
• First Posted (Estimate): November 14, 2014

Study Record Updates

• Last Update Posted (Actual): April 6, 2022
• Last Update Submitted That Met QC Criteria: April 5, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: ALS; intravenous administration; safety evaluation; 3 doses of autologous MSC
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuromuscular Diseases; Neurodegenerative Diseases; Spinal Cord Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Sclerosis; Motor Neuron Disease; Amyotrophic Lateral Sclerosis
• Other Study ID Numbers: CeTMAd/ELA/2011