Clinical trial to value the safety and efficacy of administration of stem cells derived from own patient for the treatment of Amyotrophic Lateral Sclerosis (ALS).

• Register: EUCTR
• Last refreshed on: 25 February 2013
• Main ID: EUCTR2011-006254-85-ES
• Date of registration: 09/08/2012
• Prospective Registration: Yes
• Primary sponsor: FUNDACIÓN PROGRESO Y SALUD
• Public title: Clinical trial to value the safety and efficacy of administration of stem cells derived from own patient for the treatment of Amyotrophic Lateral Sclerosis (ALS).
• Scientific title: Placebo controlled, randomized and triple blind multicentric phase I/II clinical trial to evaluate the safety, feasibility and valoration of efficacy trends of intravenous administration of three doses of autologous adipose derived autologous mesenchymal stem cells (CeTMAd) in moderate/severe ALS patients.
• Date of first enrolment: 08/02/2013
• Recruitment status: Authorised-recruitment may be ongoing or finished
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-006254-85
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

Spain

Contacts

• Name: ROSARIO MATA ALCAZAR-CABALLERO
• Affiliation: FUNDACIÓN PROGRESO Y SALUD

• Name: ROSARIO MATA ALCAZAR-CABALLERO
• Affiliation: FUNDACIÓN PROGRESO Y SALUD

Key inclusion & exclusion criteria

Inclusion criteria:
?Subjects > 18 years of age.
?Signed informed consent
?Diagnose established following the Escorial criteria from World Federation of Neurology
?Vital Capacity ? 50%
?More than 6 and less than 36 months of evolution of the disease
?Possibility of obtaining at least 50 grams of adipose tisue.
?Treated with riluzole
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 40
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 40

Exclusion criteria:
1.Any concurrent illness that could affect the measure of the clinical trial variables (hepatic, renal, cardiac insufficiency, diabetes mellitus, others)
2.Previous stem cell therapy.
3.Any lymphoproliferative disease.
4.Riluzole with 4 weeks of study entry and at any time during the study.
5.Hemophiliacs or subjects with bleeding disorders.
6.Known hypersensitivity to fetal bovine serum
7.HIV infection.
8.Serum creatinine > 3.0 in subjects not on hemodialysis.
9.Skin infection at the infusion site or systemic infection
10.Active drug or alcohol addiction
11.Pregnant, planning to become pregnant or not on accepted birth control method if subject is of child bearing potential.
12.Subjects that are breast feeding
13.Any condition that the Principal Investigator considers would render the subject unfit for the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Amyotrophic lateral sclerosis (ALS)
MedDRA version: 14.1 Level: PT Classification code 10002026 Term: Amyotrophic lateral sclerosis System Organ Class: 10029205 - Nervous system disorders

Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Intervention(s)

Product Name: Células madre mesenquimales de tejido adiposo autólogo
Pharmaceutical Form: Suspension for infusion
INN or Proposed INN: NA
CAS Number: NA
Current Sponsor code: NA
Other descriptive name: Células Mesenquimales de tejido adiposo
Concentration unit: kg kilogram(s)
Concentration type: range
Concentration number: 4000000-1000000
Pharmaceutical form of the placebo: Suspension for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: Safety evaluation and tolerability of the IV administration of 3 doses of autologous CeTMAd, measured by the ABSENCE of:
-Complications at the site of infusion
-Appearance of new neurological deficit not attributed to the natural progression of the disease:
-Adverse events (OMS scale: clinical, haematological, bioquemical)

Timepoint(s) of evaluation of this end point: Not applicable

Primary end point(s): -Adverse events (OMS scale): cuantitative variable (number of events); cualitative variable (severity)
-Complications at the site of infusion: cuantitative variable (number of events); cualitative variable (severity)
-Appearance of new neurological deficit not attributed to the natural progression of the disease: cuantitative variable (number of events); cualitative variable (severity)
-Laboratory analysis: cuantitative variables.

Secondary Objective: a) Evaluation of clinical efficacy of intravenous administration of 3 doses of autologous CeTMAd, measured by:

?Progression rate of the neurological dysfunction of the disease
?Muscle strength grading
?Changes in forced vital capacity
?Changes in muscle bulk and circumference of the upper and lower extremities:
?Changes in neurophysiological, neuropsychological and Quality of Life parameters
?Changes in the spasticity and pain measures
?Need of and time to tracheotomy or permanent assisted ventilation
?Need of and time to gastrostomy
?Overall survival, calculating time to death
b) Inmmunological effects:
?Regulatory cell populations affecting the inflammatory and tolerogenic status and
?Immunological control mechanisms mediated by TLRs.

c) Adquisition of metabolomic profiling data as an alternative tool for monitoring and identification of new markers in ALS.

Secondary Outcome(s)

Secondary end point(s): Secondary variables:
Clinical variables
? Sex: cualitative variable variable (male, female).
? Age: cuantitative variable (years)
? Age at beginning of illness: cuantitative variable (years)
? Neurological dysfunction measured by Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) at beginning of the clinical trial: cuantitative variable
?Progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALSFRS-R): cuantitative variable
?Muscle strength grading (measured by Manual Muscular Testing (MMT) and the Maximal Voluntary Isometric Contraction (MVIC): cuantitative variables
?Changes in forced vital capacity (FVC %): cuantitative variable
?Changes in upper and lower extremities circumference (cm): cuantitative variables
?Need of tracheotomy or permanent assisted ventilation: cualitative variable
?Time to tracheotomy or permanent assisted ventilation: cuantitative variable
?Overall survival, calculating time to death: cualitative variable
?Changes in the spasticity Ashworth scale: cuantitative variable
?Changes in the Visual analogue scale (VAS) of pain and in McGill Pain Questionnaire: cuantitative variable

Inmmunological análisis:

?Cellular subpopulations ( T CD4+, T CD8+, NK y monocytes): cuantitative variable (nº,%).
?IFN-?, TNF-?, IL-2, IL-12, IL-4, IL-5, IL-10, IL-17A, IL-23 and IL-6: cuantitative variables.

Neurophysiological variables: cuantitative variables:
?Changes in Neurophysiological Index (NI)
?in Motor unit number estimation (MUNE)
? in magnetic Motor evoked potentials (MEP) amplitude
?in excitability thereshold of MEP

Magnetic Resonance Imaging (MRI) variables:
?Changes in muscle bulk estimated by MRI of the upper and lower extremities: cuantitative variables
Neuropsychological variables :
?Escala de Inteligencia de Wechsler para Adultos. WAIS-III:
Variables cuantitativas
Quality of life variables:
?Changes in the quality of life measured by Sickness Impact Profile: cuantitative variable

Timepoint(s) of evaluation of this end point: Not applicable

Secondary ID(s)

CeTMad/ELA/2011

Source(s) of Monetary Support

FUNDACIÓN PROGRESO Y SALUD