Amyotrophic Lateral SclerosisPhase 1/2NCT01051882
Autologous Cultured Mesenchymal Bone Marrow Stromal Cells Secreting Neurotrophic Factors (MSC-NTF), in ALS Patients.
A Phase 1/2 study testing MSC-NTF cells transplantation (IM) and MSC-NTF cells transplantation (IT) in people with Amyotrophic Lateral Sclerosis, run by Brainstorm-Cell Therapeutics at 1 site in Israel.
Trial 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… Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Amyotrophic Lateral Sclerosis
- What is being tested?
- MSC-NTF cells transplantation (IM) and MSC-NTF cells transplantation (IT)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteIsrael
- Study dates
- Jun 2011to Mar 2013
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Conditions
- Amyotrophic Lateral Sclerosis
- Being tested
- MSC-NTF cells transplantation (IM), MSC-NTF cells transplantation (IT)
- Keywords
- Mesenchymal Stromal Cells (MSC), Amyotrophic Lateral Sclerosis (ALS), Neuroprotection, Neurodegeneration, Stem cells, ALS
- Medical subject headings
- Amyotrophic Lateral Sclerosis, Nerve Degeneration
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MSC-NTF cells transplantation (IM)Biological
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
MSC-NTF cells transplantation (IT)Biological
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 group | Role | What they receive |
|---|---|---|
| MSC-NTF cells IM | Experimental | Intramuscular administration in early stage patients Receives: Biological: MSC-NTF cells transplantation (IM) |
| MSC-NTF cells IT | Experimental | Intrathecal administration in progressive stage patients Receives: Biological: MSC-NTF cells transplantation (IT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
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.
Measured: 6 months
Secondary outcomes (8)
Changes in the progression rate of the disease as evidenced by changes in the ALS functional rating scale (ALS-FRS)
Measured: 6 months
Changes in muscle strength grading (MVIC) by muscle chart
Measured: 6 months
Changes in forced vital capacity (FVC %) (In the progressive disease stage group only).
Measured: 6 months
Changes in muscle bulk estimated by MRI of the upper and lower extremities
Measured: 6 months
Changes in upper and lower extremities circumference (cm)
Measured: 6 months
Changes in EMG parameters
Measured: 6 months
Need and time to tracheotomy or permanent assisted ventilation
Measured: 6 months
Overall survival, calculating time to death
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Jan 2010 (estimated)
- Study startJun 2011
- Primary completionDec 2012
- Study completionMar 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Amyotrophic Lateral SclerosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brainstorm-Cell Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Responsible party
- Sponsor
- Investigators
- Dimitrios Karussis, MD, PhD, Principal investigator, Hadassah Medical Organization
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01051882
- Sponsor's protocol ID
- MSC-NTF-001-HMO-CTIL
- Status last verified
- Aug 2012
- First submitted
- 17 Jan 2010
- Last updated
- 10 Jan 2019
- Results posted
- No
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.
PubMed 26751635
Study at a glance
From the registry record, last updated by the sponsor on 10 Jan 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT01051882
- Acronym / sponsor ID
- MSC-NTF-001-HMO-CTIL
- Conditions
- Amyotrophic Lateral Sclerosis
- Keywords
- Mesenchymal Stromal Cells (MSC), Amyotrophic Lateral Sclerosis (ALS), Neuroprotection, Neurodegeneration, Stem cells, ALS
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Brainstorm-Cell TherapeuticsIndustry (pharma, biotech, devices)
- Collaborators
- Hadassah Medical Organization
- Study start
- Jun 2011
- Primary completion
- Dec 2012 (actual)
- Study completion
- Mar 2013 (actual)
- First posted
- 20 Jan 2010 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| MSC-NTF cells IM | Experimental | Biological: MSC-NTF cells transplantation (IM)Intramuscular administration in early stage patients |
| MSC-NTF cells IT | Experimental | Biological: MSC-NTF cells transplantation (IT)Intrathecal administration in progressive stage patients |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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 IM |
| 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. | Biological | MSC-NTF cells IT |
Primary outcome
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.
8 secondary outcomes
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jan 2019.
- Derived from this study: PubMed 26751635Petrou 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Dimitrios Karussis, MD, PhD principal investigator
Hadassah Medical Organization
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing MSC-NTF cells transplantation (IM) and MSC-NTF cells transplantation (IT) in people with Amyotrophic Lateral Sclerosis, run by Brainstorm-Cell Therapeutics at 1 site in Israel.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Israel. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01051882, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jan 2019.