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Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in ALS Patients.
This study is currently recruiting participants.
Verified June 2011 by Hadassah Medical Organization

First Received on January 17, 2010.   Last Updated on June 22, 2011   History of Changes
Sponsor: Hadassah Medical Organization
Collaborator: Brainstorm Cell Therapeutics Ltd.
Information provided by: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT01051882
  Purpose

The study will evaluate the safety, tolerability and therapeutic effects (preliminary efficacy) of injection of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF), as a possible treatment for patients with Amyotrophic Lateral Sclerosis (ALS) at the early and progressive disease stages.


Condition Intervention Phase
Amyotrophic Lateral Sclerosis
 Biological: MSC-NTF cells transplantation (i.m.)
Biological: MSC-NTF cells transplantation (i.t.)
 Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II, Open Label Study to Evaluate Safety, Tolerability and Therapeutic Effects of Transplantation of Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in ALS Patients.

Resource links provided by NLM:

MedlinePlus related topics: Amyotrophic Lateral Sclerosis
Drug Information available for: Neurotrophin-3
U.S. FDA Resources

Further study details as provided by Hadassah Medical Organization:

Primary Outcome Measures:
  • Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) by multiple intramuscular injections (IM) at 24 separate sites on the biceps and triceps muscles to patients with ALS at the early disease stage

  • Safety evaluation and tolerability of single intrathecal injection (IT) into the cerebrospinal fluid (CSF) of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    Safety evaluation and tolerability of single intrathecal injection (IT) into the cerebrospinal fluid (CSF) of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF),to patients with ALS at the progressive disease stage.


Secondary Outcome Measures:
  • Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALS-FRS) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Changes in muscle strength grading (MVIC) by muscle chart [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Changes in forced vital capacity (FVC %) (In the progressive disease stage group only). [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Changes in muscle bulk estimated by MRI of the upper and lower extremities [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Changes in upper and lower extremities circumference (cm) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Changes in EMG parameters [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Need and time to tracheotomy or permanent assisted ventilation [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Overall survival, calculating time to death [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 24
Study Start Date: June 2011
Estimated Study Completion Date: March 2013
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: MSC-NTF Biological: MSC-NTF cells transplantation (i.m.)
In early ALS subjects: Autologous MSC-NTF cells will be transplanted under mild anesthesia, intramuscularly into patients' clinically unaffected (or only mildly affected) upper arm biceps and triceps muscles according to a pre-designed grid. Intramuscular injections will be by a 26 gauge needle to a 1.5cm depth (ensuring that injection is into muscle and not adipose tissue). The patients will be injected at 24 sites with a total of 24 million cells
Biological: MSC-NTF cells transplantation (i.t.)
In progressive ALS subjects: Autologous MSC-NTF cells will be transplanted under mild anesthesia intrathecally(via a standard lumbar puncture)with a total of 60 million cells.

Detailed Description:

This study is a single center trial to be conducted at the Department of Neurology & Laboratory of Neuroimmunology, at the Hadassah Hebrew University Medical Center, Jerusalem in Israel. All patients enrolled will have a documented history of ALS disease prior to study enrolment. Patients diagnosed as early stage ALS disease with duration of less than 6 months and patients diagnosed with progressive stage ALS disease with duration of 6-12 months. Overall, 24 patients will be recruited and allocated based on their ALS disease severity to 2 treatment groups: Group A - 12 patients of early ALS disease stage and Group B - 12 patients of progressive ALS disease.

Eligible patients will be enrolled into the study and will be observed for every 2 weeks during a "run in period" of 3 months for determination of the progression rate of the disease. During the "run in period" after about 6 weeks following enrollment, patients of both study groups will undergo a Bone Marrow Aspiration 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 of both study groups will undergo the treatment and MSC-NTF will be transplanted by IM or IT injection to the early and progressive ALS patients respectively.

After the MSC-NTF transplantation patients will be observed on a monthly basis for a post treatment follow up period of 6 months.

  Eligibility

Ages Eligible for Study:   20 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. El Escorial criteria for definite or probable ALS
  2. Either men or non pregnant women between 20-75 years of age.
  3. Patient is mentally intact and psychologically stable
  4. For early stage ALS- Patients will be with ALS-FRS-R scale of at least 30 and disease duration of less than 2 years.Or, for progressive stage ALS- Patients will be with an ALS-FRS-R scale of 15-30 and disease duration of less than 2 years
  5. For early stage ALS- Patient has sufficiently bulky muscles. Or, for progressive stage ALS- Patient with at least 60% FVC
  6. Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.

Exclusion Criteria:

  1. Positive test for HBV, HCV, HIV and Mycoplasma.
  2. High protein in the CSF.
  3. Lymphocytosis in the CSF.
  4. 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.
  7. Renal failure, impaired hepatic function
  8. Patients suffering from significant cardiac disease, malignant diseases or any other disease that may risk the patient or interfere with the ability to interpret the results
  9. Active infections.
  10. Participation in another clinical trial within 1 month prior to start of this study.
  11. Subject unwilling or unable to comply with the requirements of the protocol.
  12. Patient has not been treated previously with any cellular therapy.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01051882

Contacts
Contact: Dimitrios Karussis, MD, PhD +972-2-6776939 karus@cc.huji.ac.il
Contact: Adi Vaknin-Dembinsky, MD, PhD +972-2-6776939 adembinsky@yahoo.com

Locations
Israel
Hadassah Medical Organization Recruiting
Jerusalem, Israel, 91120
Contact: Dimitrios Karussis, MD, PhD     +972-2-6776939     karus@cc.huji.ac.il    
Sponsors and Collaborators
Hadassah Medical Organization
Brainstorm Cell Therapeutics Ltd.
Investigators
Principal Investigator: Dimitrios Karussis, MD, PhD Hadassah Medical Organization
  More Information

No publications provided

Responsible Party: Adrian Harel, Brainstorm Cell Therapeutics Ltd.
ClinicalTrials.gov Identifier: NCT01051882     History of Changes
Other Study ID Numbers: MSC-NTF-001-HMO-CTIL
Study First Received: January 17, 2010
Last Updated: June 22, 2011
Health Authority: Israel: Ministry of Health

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

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

ClinicalTrials.gov processed this record on May 24, 2012



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