Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 1 for:    nct01051882
Previous Study | Return to List | Next Study

Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in ALS Patients.

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.
ClinicalTrials.gov Identifier: NCT01051882
Recruitment Status : Completed
First Posted : January 20, 2010
Last Update Posted : January 10, 2019
Sponsor:
Collaborator:
Hadassah Medical Organization
Information provided by (Responsible Party):
Brainstorm-Cell Therapeutics

Tracking Information
First Submitted Date  ICMJE January 17, 2010
First Posted Date  ICMJE January 20, 2010
Last Update Posted Date January 10, 2019
Study Start Date  ICMJE June 2011
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 27, 2011)
  • 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 ]
    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 ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: January 19, 2010)
To evaluate the safety and tolerability of a single autologous transplantation into the CSF (intrathecal) or the muscles, of adult human bone marrow derived MSC secreting neurotrophic factors (hMSC-NTF cells) in patients with ALS. [ Time Frame: 6-12 months ]
Change History Complete list of historical versions of study NCT01051882 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: June 2, 2010)
  • Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALS-FRS) [ Time Frame: 6 months ]
  • Changes in muscle strength grading (MVIC) by muscle chart [ Time Frame: 6 months ]
  • Changes in forced vital capacity (FVC %) (In the progressive disease stage group only). [ Time Frame: 6 months ]
  • Changes in muscle bulk estimated by MRI of the upper and lower extremities [ Time Frame: 6 months ]
  • Changes in upper and lower extremities circumference (cm) [ Time Frame: 6 months ]
  • Changes in EMG parameters [ Time Frame: 6 months ]
  • Need and time to tracheotomy or permanent assisted ventilation [ Time Frame: 6 months ]
  • Overall survival, calculating time to death [ Time Frame: 6 months ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 19, 2010)
Changes in the progression rate of the disease as evidenced by changes in muscle strength, in the ALS functional rating scale (ALS-FRS), in forced vital capacity (FVC%)', quantitative EMG, muscle bulk estimation by MRI, and overall survival. [ Time Frame: 6-12 months ]
Current Other Outcome Measures  ICMJE Not Provided
Original Other Outcome Measures  ICMJE Not Provided
 
Descriptive Information
Brief Title  ICMJE Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in ALS Patients.
Official Title  ICMJE 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.
Brief Summary 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.
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.

Study Type  ICMJE Interventional
Study Phase Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Amyotrophic Lateral Sclerosis
Intervention  ICMJE
  • Biological: MSC-NTF cells transplantation (IM)
    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 (IT)
    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.
Study Arms
  • Experimental: MSC-NTF cells IM
    Intramuscular administration in early stage patients
    Intervention: Biological: MSC-NTF cells transplantation (IM)
  • Experimental: MSC-NTF cells IT
    Intrathecal administration in progressive stage patients
    Intervention: Biological: MSC-NTF cells transplantation (IT)
Publications * Petrou P, Gothelf Y, Argov Z, Gotkine M, Levy YS, Kassis I, Vaknin-Dembinsky A, Ben-Hur T, Offen D, Abramsky O, Melamed E, Karussis D. Safety and Clinical Effects of Mesenchymal Stem Cells Secreting Neurotrophic Factor Transplantation in Patients With Amyotrophic Lateral Sclerosis: Results of Phase 1/2 and 2a Clinical Trials. JAMA Neurol. 2016 Mar;73(3):337-44. doi: 10.1001/jamaneurol.2015.4321.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: July 2, 2013)
12
Original Estimated Enrollment  ICMJE
 (submitted: January 19, 2010)
24
Actual Study Completion Date March 2013
Actual Primary Completion Date December 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender
Sexes Eligible for Study: All
Ages 20 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Israel
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01051882
Other Study ID Numbers  ICMJE MSC-NTF-001-HMO-CTIL
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement Not Provided
Responsible Party Brainstorm-Cell Therapeutics
Study Sponsor  ICMJE Brainstorm-Cell Therapeutics
Collaborators  ICMJE Hadassah Medical Organization
Investigators  ICMJE
Principal Investigator: Dimitrios Karussis, MD, PhD Hadassah Medical Organization
PRS Account Brainstorm-Cell Therapeutics
Verification Date August 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP