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Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS)

The recruitment status of this study is unknown. The completion date has passed and the status has not been verified in more than two years.
Verified January 2014 by Hadassah Medical Organization.
Recruitment status was:  Active, not recruiting
Sponsor:
ClinicalTrials.gov Identifier:
NCT01777646
First Posted: January 29, 2013
Last Update Posted: February 5, 2014
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Brainstorm-Cell Therapeutics
Information provided by (Responsible Party):
Hadassah Medical Organization
  Purpose
The study will evaluate the safety, tolerability and therapeutic effects of transplantation of escalating doses of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), in patients with amyotrophic lateral sclerosis (ALS).

Condition Intervention Phase
Amyotrophic Lateral Sclerosis Biological: MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase IIa, Open Label, Dose-escalating Clinical Study to Evaluate the Safety, Tolerability and Therapeutic Effects of Transplantation of Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in Patients With Amyotrophic Lateral Sclerosis (ALS).

Resource links provided by NLM:


Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Safety evaluation and tolerability of a single treatment administration in an escalating-dose of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) [ Time Frame: At baseline and up to 6 month following treatment administration ]

Secondary Outcome Measures:
  • Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale [ Time Frame: At baseline and up to 6 month following treatment administration ]
  • Changes in muscle strength grading (MVIC) by muscle chart [ Time Frame: At baseline and up to 6 month following treatment administration ]
  • Changes in muscle bulk estimated by MRI of the upper and lower extremities [ Time Frame: At baseline and up to 6 month following treatment administration ]
  • Change in upper and lower extremities circumference (cm) [ Time Frame: At baseline and up to 6 month following treatment administration ]
  • Changes in EMG parameters [ Time Frame: At baseline and up to 6 month following treatment administration ]

Estimated Enrollment: 14
Study Start Date: December 2012
Estimated Study Completion Date: October 2014
Estimated Primary Completion Date: September 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSC-NTF Biological: MSC_NTF cells transplantation by multiple intramuscular injections at 24 separate sites, in addition to a single intrathechal injection into the CSF

Detailed Description:

This is a phase IIa prospective, open label, dose-escalating, three patient-group clinical study, to evaluate the safety, tolerability and preliminary efficacy of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a potent treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early disease stages. This study is a single center trial. It is anticipated that the study will be conducted at the Department of Neurology & Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem in Israel. In addition, ALS patients could also be referred to the clinical site above by other medical centers.

All patients enrolled will have a documented history of ALS disease prior to study enrollment. Patients diagnosed as early stage ALS disease with duration of less than 2 years. ALS patients identified as "predisposed" will be approached and requested to sign an Informed Consent Form (ICF). Overall, 14 patients will be recruited.

Treatment will start with the lowest dose (94x106 cells) and the dose will be increased to the next medium and high dose (141x106 and 188x106 respectively), for the next patients group only following safety analysis.

The expected duration of patient screening period prior to enrollment into this study is in-between two weeks up to 2 days prior to the study enrollment day during visit 2 (verification of compliance with inclusion/exclusion criteria including clinical laboratory results). Eligible patients will be enrolled into the study and will be observed for every month during a "run in period" of 3 months for determination of the progression rate of the disease (allowing a time window of ± 5 days for all visits). During the "run in period" after about 6 weeks following enrollment, patients of both study groups will undergo a Bone Marrow Aspiration (BMA) procedure and MSC-NTF cells will be produced from the bone marrow aspirate based on Brainstorm Cell Therapeutics Ltd proprietary method. On the last "run in period" visit, patients will undergo the treatment and MSC-NTF will be transplanted by IM+IT to the early ALS patients.

After the MSC-NTF transplantation patients will be observed on a monthly basis for a post treatment follow up period of 6 months (allowing a time window of ± 5 days for all visits). Treatment safety, adverse events and exploratory parameters, to establish ALS progression rate assessment of the disease will be recorded throughout the duration of the "run in period" and the post treatment follow up period.

  Eligibility

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Ages Eligible for Study:   20 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Patient must fulfill El Escorial criteria (APPENDIX 2) for definite or probable ALS (sporadic and not familial)
  2. Participants, either men or non pregnant women are between 20 and 75 years of age.
  3. The patient is mentally intact and psychologically stable
  4. Patients will be with an ALS-FRS-R scale (APPENDIX 3) of at least 30 and disease duration of less than 2 years.
  5. Patient has sufficiently bulky muscles.
  6. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.

Exclusion Criteria:

  1. Patient has a positive test for HBV, HCV or HIV.
  2. Patient has high protein in the CSF (Protein > 70 mg/ml).
  3. Patient has lymphocytosis in the CSF (lymphocytes > 5/ml).
  4. Patient is positive for anti-GM1 antibodies.
  5. Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
  6. The patient is a respiratory dependent patient.
  7. Patients with renal failure (Cr > 2 mg/dl).
  8. Patients with impaired hepatic function (ALT, AST or GGT 2-fold higher than normal upper limit).
  9. Patients suffering from significant cardiac disease, malignant disease or any other disease that may risk the patient or interfere with the ability to interpret the results
  10. Patient with active infections.
  11. Participation in another clinical trial within 1 month prior to start of this study.
  12. Patient has not been treated previously with any cellular therapy.
  13. Subject unwilling or unable to comply with the requirements of the protocol.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01777646


Locations
Israel
Hadassah Medical Organization
Jerusalem, Israel, 91120
Sponsors and Collaborators
Hadassah Medical Organization
Brainstorm-Cell Therapeutics
Investigators
Principal Investigator: Dimitrios Karusis, MD, PhD Hadassah Medical Organization
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01777646     History of Changes
Other Study ID Numbers: MSC-NTF-002-HMO-CTIL
First Submitted: December 12, 2012
First Posted: January 29, 2013
Last Update Posted: February 5, 2014
Last Verified: January 2014

Keywords provided by Hadassah Medical Organization:
Mesenchymal Strmal Cells (MSC)
Amyotrophic Lateral Sclerosis (ALS)
Neuroprotection
Neurodegeneration
Stem cells

Additional relevant MeSH terms:
Sclerosis
Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases