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Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis (TCIM/ELA)

Primary Purpose

ALS (Amyotrophic Lateral Sclerosis)

Status
Unknown status
Phase
Phase 1
Locations
Spain
Study Type
Interventional
Intervention
MNC (Mononuclear cells)
Saline
Sponsored by
Red de Terapia Celular
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for ALS (Amyotrophic Lateral Sclerosis)

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Diagnosis of definite or probable ALS according to the criteria established by the World Federation of Neurology
  • Patient that provides reasonable assurance of adherence to protocol.
  • Neurophysiological data confirming affectation of lower motor neurons in the lumbar region.
  • Assessment of motor deficits in dorsiflexion of both feet (4 or 5 points on the MRC scale)
  • The patient must fulfill all inclusion criteria.

Exclusion Criteria:

  • Diabetes Mellitus.
  • Other diseases that may present with polyneuropathy.
  • Previous history of stroke.
  • Prior Pathology of the peripheral nervous system affecting one or both lower limbs with or without clinically evident neurological sequelae.
  • Pregnant or breastfeeding patients active.
  • Patients physiologically capable of becoming pregnant, unless they are using reliable contraception.
  • Patients with cardiac disease, renal, hepatic, systemic, immune that may influence patient survival during the test.
  • Positive serology for hepatitis B, hepatitis C or HIV.
  • Clinical and anesthesiologic Criteria, contraindicating either sedation or extraction of MO (Altered coagulation system or anticoagulated patient with inability to withdraw anticoagulation, hemodynamic instability, altered skin puncture site, etc.)
  • Included in other clinical trials in the last 6 months.

Sites / Locations

  • Clinical Universitary Hospital Virgen de la Arrixaca

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

MNC (Mononuclear cells)

Saline

Arm Description

All patients included in the clinical trial will receive an intramuscular infusion of autologous mononuclear cells (MNC) of Bone Marrow (BM) in TA muscle of one of the lower limb (experimental group). The lower limb on the CMN infuse autologous BM will be determined randomly. The average dose is 550 millions of cells (100-1200 million) diluted in 2 ml. saline

All patients included in the clinical trial will receive an intramuscular infusion of 2 mL of saline (placebo) in the TA muscle of the contralateral limb (group control).

Outcomes

Primary Outcome Measures

Rate of serious and non-serious adverse events related to the use of bone marrow mononuclear cells in patients with Amyotrophic Lateral Sclerosis.

Secondary Outcome Measures

Estimated number of motor units (MUNE)
Several techniques for estimating the MUNE, all based on the relationship between the amplitude or area of compound muscle action potential (CMAP) and amplitude or area corresponding to a single motor unit response. The differences between the techniques are due to the different ways of estimating the amplitude of the responses for individual motor units. The study will use two techniques: Incremental Technique: The unitary amplitude (or area) of individual motor units are calculated from the responses to increasing intensities stimuli near of intensity threshold (Dantes and McComas, 1991) Statistical technique: The unit amplitude (or area) of the individual motor units are calculated from the amplitude variations (or area) of the muscle action potential obtained in response to stimuli from a fixed intensity (Daube, 2006)
Compound muscle action potential (CMAP)
CMAP is registered after supramaximal stimulation intensity (0.1-0.2 ms pulses at 1 Hz) of the common peroneal nerve at the level of the head of the fibula. The electrical stimulus is placed in a fixed position during the entire registration process. CMAP will be recorded simultaneously in 5 positions along longitudinally oriented TA muscle. To determine these 5 positions bony landmarks that are reproducible between members and between different patients will be used.
Fiber density (FD)
Quantifies the average number of muscle fibers per motor unit. It is obtained from single fiber recordings made with electrodes. The average number of motor unit potentials is calculated in 20 different positions in the muscle.
Muscle force MRC (Medical Research Council) score
Maximum force developed in an isometric contraction of the tibialis anterior (TA) muscle.
The measurement will be done in Newtons, with a dynamometer during dorsiflexion of the foot (from certain angles).
Maximum transversal area of the tibialis anterior (TA)
The area will be measured in cm2 by echography.

Full Information

First Posted
October 24, 2014
Last Updated
March 29, 2017
Sponsor
Red de Terapia Celular
Collaborators
Spanish National Health System, Hospital Universitario Virgen de la Arrixaca, Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia, Public Health Service, Murcia, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca
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1. Study Identification

Unique Protocol Identification Number
NCT02286011
Brief Title
Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis
Acronym
TCIM/ELA
Official Title
Phase I Clinical Trial on Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis.
Study Type
Interventional

2. Study Status

Record Verification Date
March 2017
Overall Recruitment Status
Unknown status
Study Start Date
November 2014 (undefined)
Primary Completion Date
December 2017 (Anticipated)
Study Completion Date
December 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Red de Terapia Celular
Collaborators
Spanish National Health System, Hospital Universitario Virgen de la Arrixaca, Fundacion para la Formacion e Investigacion Sanitarias de la Region de Murcia, Public Health Service, Murcia, Instituto Murciano de Investigación Biosanitaria Virgen de la Arrixaca

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to evaluate the safety of Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis by a prospective, single-center, randomized, parallel, double-blind, placebo-controlled phase I clinical trial.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
ALS (Amyotrophic Lateral Sclerosis)

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
20 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
MNC (Mononuclear cells)
Arm Type
Experimental
Arm Description
All patients included in the clinical trial will receive an intramuscular infusion of autologous mononuclear cells (MNC) of Bone Marrow (BM) in TA muscle of one of the lower limb (experimental group). The lower limb on the CMN infuse autologous BM will be determined randomly. The average dose is 550 millions of cells (100-1200 million) diluted in 2 ml. saline
Arm Title
Saline
Arm Type
Placebo Comparator
Arm Description
All patients included in the clinical trial will receive an intramuscular infusion of 2 mL of saline (placebo) in the TA muscle of the contralateral limb (group control).
Intervention Type
Biological
Intervention Name(s)
MNC (Mononuclear cells)
Intervention Description
The cells are infused into the TA muscle of the lower limb randomized as Group A (experimental) intramuscularly. The infusion is made with a needle, 26 gauge, at 4 points of the TA muscle a specific depth given by the neurophysiological study. The total volume infused will be 2 ml, 0.5 ml at each point. For infusion is as painless as possible for the patient to comply exactly with stereotactic indications of neurophysiology, the infusion was made at a uniform controlled rate and for this, the syringe is placed on a Yesargil arm, equipped with a microinjector and controlled infusion device.
Intervention Type
Other
Intervention Name(s)
Saline
Intervention Description
The placebo, 2ml of saline, will be infused like in the experimental arm.
Primary Outcome Measure Information:
Title
Rate of serious and non-serious adverse events related to the use of bone marrow mononuclear cells in patients with Amyotrophic Lateral Sclerosis.
Time Frame
24 months from baseline
Secondary Outcome Measure Information:
Title
Estimated number of motor units (MUNE)
Description
Several techniques for estimating the MUNE, all based on the relationship between the amplitude or area of compound muscle action potential (CMAP) and amplitude or area corresponding to a single motor unit response. The differences between the techniques are due to the different ways of estimating the amplitude of the responses for individual motor units. The study will use two techniques: Incremental Technique: The unitary amplitude (or area) of individual motor units are calculated from the responses to increasing intensities stimuli near of intensity threshold (Dantes and McComas, 1991) Statistical technique: The unit amplitude (or area) of the individual motor units are calculated from the amplitude variations (or area) of the muscle action potential obtained in response to stimuli from a fixed intensity (Daube, 2006)
Time Frame
24 months from baseline
Title
Compound muscle action potential (CMAP)
Description
CMAP is registered after supramaximal stimulation intensity (0.1-0.2 ms pulses at 1 Hz) of the common peroneal nerve at the level of the head of the fibula. The electrical stimulus is placed in a fixed position during the entire registration process. CMAP will be recorded simultaneously in 5 positions along longitudinally oriented TA muscle. To determine these 5 positions bony landmarks that are reproducible between members and between different patients will be used.
Time Frame
24 months from baseline
Title
Fiber density (FD)
Description
Quantifies the average number of muscle fibers per motor unit. It is obtained from single fiber recordings made with electrodes. The average number of motor unit potentials is calculated in 20 different positions in the muscle.
Time Frame
24 months from baseline
Title
Muscle force MRC (Medical Research Council) score
Time Frame
24 months from baseline
Title
Maximum force developed in an isometric contraction of the tibialis anterior (TA) muscle.
Description
The measurement will be done in Newtons, with a dynamometer during dorsiflexion of the foot (from certain angles).
Time Frame
24 months from baseline
Title
Maximum transversal area of the tibialis anterior (TA)
Description
The area will be measured in cm2 by echography.
Time Frame
24 months from baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Diagnosis of definite or probable ALS according to the criteria established by the World Federation of Neurology Patient that provides reasonable assurance of adherence to protocol. Neurophysiological data confirming affectation of lower motor neurons in the lumbar region. Assessment of motor deficits in dorsiflexion of both feet (4 or 5 points on the MRC scale) The patient must fulfill all inclusion criteria. Exclusion Criteria: Diabetes Mellitus. Other diseases that may present with polyneuropathy. Previous history of stroke. Prior Pathology of the peripheral nervous system affecting one or both lower limbs with or without clinically evident neurological sequelae. Pregnant or breastfeeding patients active. Patients physiologically capable of becoming pregnant, unless they are using reliable contraception. Patients with cardiac disease, renal, hepatic, systemic, immune that may influence patient survival during the test. Positive serology for hepatitis B, hepatitis C or HIV. Clinical and anesthesiologic Criteria, contraindicating either sedation or extraction of MO (Altered coagulation system or anticoagulated patient with inability to withdraw anticoagulation, hemodynamic instability, altered skin puncture site, etc.) Included in other clinical trials in the last 6 months.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Joaquín A Gómez Espuch, MD
Organizational Affiliation
Hospital Universitario Virgen de la Arrixaca
Official's Role
Principal Investigator
Facility Information:
Facility Name
Clinical Universitary Hospital Virgen de la Arrixaca
City
El Palmar
State/Province
Murcia
ZIP/Postal Code
30120
Country
Spain

12. IPD Sharing Statement

Citations:
PubMed Identifier
22415951
Citation
Blanquer M, Moraleda JM, Iniesta F, Gomez-Espuch J, Meca-Lallana J, Villaverde R, Perez-Espejo MA, Ruiz-Lopez FJ, Garcia Santos JM, Bleda P, Izura V, Saez M, De Mingo P, Vivancos L, Carles R, Jimenez J, Hernandez J, Guardiola J, Del Rio ST, Antunez C, De la Rosa P, Majado MJ, Sanchez-Salinas A, Lopez J, Martinez-Lage JF, Martinez S. Neurotrophic bone marrow cellular nests prevent spinal motoneuron degeneration in amyotrophic lateral sclerosis patients: a pilot safety study. Stem Cells. 2012 Jun;30(6):1277-85. doi: 10.1002/stem.1080.
Results Reference
result
PubMed Identifier
32265627
Citation
Geijo-Barrientos E, Pastore-Olmedo C, De Mingo P, Blanquer M, Gomez Espuch J, Iniesta F, Iniesta NG, Garcia-Hernandez A, Martin-Estefania C, Barrios L, Moraleda JM, Martinez S. Intramuscular Injection of Bone Marrow Stem Cells in Amyotrophic Lateral Sclerosis Patients: A Randomized Clinical Trial. Front Neurosci. 2020 Mar 24;14:195. doi: 10.3389/fnins.2020.00195. eCollection 2020.
Results Reference
derived

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Intramuscular Infusion of Autologous Bone Marrow Stem Cells in Patients With Amyotrophic Lateral Sclerosis

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