Biological Treatment of Amyotrophic Lateral Sclerosis (NeuStem-ALS)

Safety/Efficacy Study for the Biological Treatment of Amyotrophic Lateral Sclerosis With Autologous Stem/Progenitor Cells

The purpose of this study is to test the safety and effectiveness of an autologous bone marrow-derived stem/progenitor cells infusion in the subjects with diagnosed amyotrophic lateral sclerosis.

Study Overview

• Status: Unknown
• Conditions: Amyotrophic Lateral Sclerosis
• Intervention / Treatment: Other: Biological: Cell-based therapeutics; Other: Symptomatic treatment of ALS

Detailed Description

Amyotrophic lateral sclerosis (ALS) is a universally fatal neurodegenerative condition that causes weakness leading to paralysis and death. Life expectancy is less that 5 years. The cause is generally unknown and there is no effective treatment. Patients with ALS typically exhibit a progressive paralysis due to the continued loss of motoneurons. Intraspinal injections of bone marrow mononuclear cells have been able to ameliorate the course of ALS in murine models. The purpose of this prospective, nonrandomized, open label, pilot study is to conduct the investigation of the safety and efficacy of infusion of autologous bone marrow-isolated stem/progenitor cells with different selected phenotypes into the subjects with diagnosed ALS. Especially, this clinical trial is designated to test the therapeutic (pro-regenerative and neuro-protective) functions of different stem/progenitor cell populations able to secrete bioactive neurotrophic factors. All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage of ALS with the duration of disease less than 6 months and patients diagnosed with advanced stage of ALS disease with duration of 6-12 months will be recruited and allocated based on their disease severity to two treatment groups: Group I - patients of early ALS disease stage and Group II - patients of advanced ALS disease. Next, autologous bone marrow-isolated stem/progenitor cells administration to the cerebrospinal fluid at the site of the spinal cord will be performed. Finally, treatment safety, adverse events and exploratory parameters, including electromyographic (EMG) studies, forced vital capacity (FVC), functional rating scale (FRS) and maximum voluntary isometric contraction-arm (MVIC-arm) evaluation, to establish ALS progression rate will be recorded throughout the duration of the post-treatment follow up period.

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Phase 1

Contacts and Locations

Study Locations

• Poland
  • Szczecin, Poland, 71-252
    • Department of Neurology of Pomeranian Medical University in Szczecin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• diagnosis of the ALS disease before the cell transplantation (diagnose established following the El Escorial criteria for definite ALS)
• good understanding of the protocol and willingness to consent
• patient is mentally intact and psychologically stable
• signed informed consent

Exclusion Criteria:

Concomitant of other systemic disease or diseases:

• inflammation (high protein or lymphocytosis in the CSF), active infections.
• diabetes,
• cardio-vascular disorders,
• cancer,
• autoimmune diseases
• renal failure,
• impaired hepatic function.
• subject is a respiratory dependent.
• subject unwilling or unable to comply with the requirements of the protocol.
• patient has been treated previously with any cellular therapy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Stem/progenitor cells transplantation.; Intervention: Biological: Cell-based therapeutics Autologous bone marrow-derived stem/progenitor cells will be transplanted intrathecally (via a standard lumbar puncture) into early vs. progressive ALS subjects.	Other: Biological: Cell-based therapeutics; Human autologous bone marrow-derived stem/progenitor cell transplantation in ALS patients.
Sham Comparator: Standard treatment of ALS; Symptomatic treatment of ALS without biologic cell-based treatment	Other: Symptomatic treatment of ALS; Symptomatic neurological treatment of ALS

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety of autologous bone marrow stem/progenitor cell infusion in enrolled patients	Confirm the safety of autologous bone marrow stem/progenitor cell infusion in enrolled patients by repeated follow-up over one year with clinical and laboratory evaluations.	1 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Efficacy of autologous bone marrow stem/progenitor cell infusion in enrolled patients.	Confirm the efficacy of autologous bone marrow stem/progenitor cell infusion in enrolled patients by repeated follow-up over one year with clinical and laboratory evaluation tests for neurodegeneration processes analysis and general health outcomes.	1 year

Collaborators and Investigators

• Sponsor: Pomeranian Medical University Szczecin
• Investigators: Study Director: Boguslaw Machalinski, MD, PhD, Pomeranian Medical University Szczecin; Study Chair: Przemyslaw Nowacki, MD, PhD, Pomeranian Medical University Szczecin

Publications and helpful links

General Publications

• Pawlukowska W, Baumert B, Golab-Janowska M, Meller A, Machowska-Sempruch K, Welnicka A, Paczkowska E, Rotter I, Machalinski B, Nowacki P. Comparative assessment and monitoring of deterioration of articulatory organs using subjective and objective tools among patients with amyotrophic lateral sclerosis. BMC Neurol. 2019 Oct 19;19(1):241. doi: 10.1186/s12883-019-1484-2.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: July 16, 2014
• First Submitted That Met QC Criteria: July 17, 2014
• First Posted (Estimate): July 18, 2014

Study Record Updates

• Last Update Posted (Estimate): July 18, 2014
• Last Update Submitted That Met QC Criteria: July 17, 2014
• Last Verified: July 1, 2014

More Information

Terms related to this study

• Keywords: cell-based therapy; autologous bone marrow-derived stem/progenitor cells; stem cell infusion, stem cell transplantation; biological therapy with neurotrophic factors; bioactive neurotrophic factors
• 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; Dermatologic Agents; Keratolytic Agents; Coal Tar
• Other Study ID Numbers: ZPO 02; ZPO 02, ALS-BMSC #01 (Other Identifier: Department of General Pathology, PMU in Szczecin)