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

Phase 1

• Conditions: ALS (Amyotrophic Lateral Sclerosis)
• Interventions: Biological: MNC (Mononuclear cells); Other: Saline

• Registration Number: NCT02286011
• Lead Sponsor: Red de Terapia Celular

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-24
• Study Start: 2014-11
• Study First Submitted QC: 2014-11-06
• Study First Posted: 2014-11-07
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-29
• Last Update Posted: 2017-03-30
• Primary Completion: 2017-12
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
MNC (Mononuclear cells)	MNC (Mononuclear cells)	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
Saline	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).

Primary Outcome Measures

Name	Time	Method
Rate of serious and non-serious adverse events related to the use of bone marrow mononuclear cells in patients with Amyotrophic Lateral Sclerosis.	24 months from baseline

Secondary Outcome Measures

Name	Time	Method
Muscle force MRC (Medical Research Council) score	24 months from baseline
Estimated number of motor units (MUNE)	24 months from baseline	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)	24 months from baseline	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)	24 months from baseline	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.
Maximum force developed in an isometric contraction of the tibialis anterior (TA) muscle.	24 months from baseline	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)	24 months from baseline	The area will be measured in cm2 by echography.

Trial Locations

Locations (1)

Clinical Universitary Hospital Virgen de la Arrixaca; 🇪🇸 El Palmar, Murcia, Spain