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

Primary Purpose

Amyotrophic Lateral Sclerosis

Status

Completed

Phase

Phase 1

Locations

Israel

Study Type

Interventional

Intervention

MSC-NTF cells transplantation (IM)

MSC-NTF cells transplantation (IT)

About this trial

This is an interventional treatment trial for Amyotrophic Lateral Sclerosis focused on measuring Mesenchymal Stromal Cells (MSC), Amyotrophic Lateral Sclerosis (ALS), Neuroprotection, Neurodegeneration, Stem cells, ALS

Eligibility Criteria

20 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

El Escorial criteria for definite or probable ALS
Either men or non pregnant women between 20-75 years of age.
Patient is mentally intact and psychologically stable
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
For early stage ALS- Patient has sufficiently bulky muscles. Or, for progressive stage ALS- Patient with at least 60% FVC
Participant understands the nature of the procedure and provides written informed consent prior to any study procedure.

Exclusion Criteria:

Positive test for HBV, HCV, HIV and Mycoplasma.
High protein in the CSF.
Lymphocytosis in the CSF.
Positive for anti-GM1 antibodies.
Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies.
The patient is a respiratory dependent.
Renal failure, impaired hepatic function
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
Active infections.
Participation in another clinical trial within 1 month prior to start of this study.
Subject unwilling or unable to comply with the requirements of the protocol.
Patient has not been treated previously with any cellular therapy.

Sites / Locations

Hadassah Medical Organization

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Arm Label

MSC-NTF cells IM

MSC-NTF cells IT

Arm Description

Intramuscular administration in early stage patients

Intrathecal administration in progressive stage patients

Outcomes

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)

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)

Secondary Outcome Measures

Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALS-FRS)

Changes in muscle strength grading (MVIC) by muscle chart

Changes in forced vital capacity (FVC %) (In the progressive disease stage group only).

Changes in muscle bulk estimated by MRI of the upper and lower extremities

Changes in upper and lower extremities circumference (cm)

Changes in EMG parameters

Need and time to tracheotomy or permanent assisted ventilation

Overall survival, calculating time to death

Full Information

NCT ID

NCT01051882

First Posted

January 17, 2010

Last Updated

January 8, 2019

Sponsor

Brainstorm-Cell Therapeutics

Collaborators

Hadassah Medical Organization

1. Study Identification

Unique Protocol Identification Number

NCT01051882

Brief Title

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

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.

Study Type

Interventional

2. Study Status

Record Verification Date

August 2012

Overall Recruitment Status

Completed

Study Start Date

June 2011 (undefined)

Primary Completion Date

December 2012 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Brainstorm-Cell Therapeutics

Collaborators

Hadassah Medical Organization

4. Oversight

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Amyotrophic Lateral Sclerosis

Keywords

Mesenchymal Stromal Cells (MSC), Amyotrophic Lateral Sclerosis (ALS), Neuroprotection, Neurodegeneration, Stem cells, ALS

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

12 (Actual)

8. Arms, Groups, and Interventions

Arm Title

MSC-NTF cells IM

Arm Type

Experimental

Arm Description

Intramuscular administration in early stage patients

Arm Title

MSC-NTF cells IT

Arm Type

Experimental

Arm Description

Intrathecal administration in progressive stage patients

Intervention Type

Biological

Intervention Name(s)

MSC-NTF cells transplantation (IM)

Intervention Description

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

Intervention Type

Biological

Intervention Name(s)

MSC-NTF cells transplantation (IT)

Intervention Description

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.

Primary Outcome Measure Information:

Title

Safety evaluation and tolerability of a single treatment administration of autologous cultured mesenchymal bone marrow stromal cells secreting neurotrophic factors (MSC-NTF)

Description

Time Frame

6 months

Title

Description

Time Frame

6 months

Secondary Outcome Measure Information:

Title

Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALS-FRS)

Time Frame

6 months

Title

Changes in muscle strength grading (MVIC) by muscle chart

Time Frame

6 months

Title

Changes in forced vital capacity (FVC %) (In the progressive disease stage group only).

Time Frame

6 months

Title

Changes in muscle bulk estimated by MRI of the upper and lower extremities

Time Frame

6 months

Title

Changes in upper and lower extremities circumference (cm)

Time Frame

6 months

Title

Changes in EMG parameters

Time Frame

6 months

Title

Need and time to tracheotomy or permanent assisted ventilation

Time Frame

6 months

Title

Overall survival, calculating time to death

Time Frame

6 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

20 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: El Escorial criteria for definite or probable ALS Either men or non pregnant women between 20-75 years of age. Patient is mentally intact and psychologically stable 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 For early stage ALS- Patient has sufficiently bulky muscles. Or, for progressive stage ALS- Patient with at least 60% FVC Participant understands the nature of the procedure and provides written informed consent prior to any study procedure. Exclusion Criteria: Positive test for HBV, HCV, HIV and Mycoplasma. High protein in the CSF. Lymphocytosis in the CSF. Positive for anti-GM1 antibodies. Patient has significant conduction blocks or slow nerve conduction velocities (a reduction of more than 30%) confirmed by nerve conduction velocity - EMG studies. The patient is a respiratory dependent. Renal failure, impaired hepatic function 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 Active infections. Participation in another clinical trial within 1 month prior to start of this study. Subject unwilling or unable to comply with the requirements of the protocol. Patient has not been treated previously with any cellular therapy.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Dimitrios Karussis, MD, PhD

Organizational Affiliation

Hadassah Medical Organization

Official's Role

Principal Investigator

Facility Information:

Facility Name

Hadassah Medical Organization

City

Jerusalem

ZIP/Postal Code

91120

Country

Israel

12. IPD Sharing Statement

Citations:

PubMed Identifier

26751635

Citation

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.

Results Reference

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

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