Multiple SclerosisPhase 1/2MSC-pMSNCT04823000
Effects of Repeated Mesenchymal Stem Cells (MSC) in Patients With Progressive Multiple Sclerosis
A Phase 1/2 study testing Mesenchymal Stem Cells (MSC) in people with Multiple Sclerosis, run by Hadassah Medical Organization.
Trial summary
An open prospective study with multiple (every 6-12 months) intrathecal or intravenous injections of autologous MSC in patients with progressive forms of MS (secondary progressive, primary progressive or relapsing-progressive), who failed to respond to first and second lines of immunomodulatory treatments and… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Multiple Sclerosis
- What is being tested?
- Mesenchymal Stem Cells (MSC)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2013to 1 Apr 2020
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Consenting patients fulfilling the Poser's criteria for definite MS
- Age 18-70
- Male and female
- EDSS rate 5.5-7.5 (moderate to high disability)
- Failure to two lines of the currently available registered immunomodulatory treatments for MS. The lack of response to these treatments was determined by either an increase in EDSS or the appearance of at least two relapses of MS during the year prior to inclusion.
Who cannot join
- Patients who were treated with cytotoxic medications during the last three months prior to the infusion.
- Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results.
- Patients with active infections.
- Patients with cognitive decline or inability to understand and sign the informed consent.
About this study
Official title: Long Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cells (MSC) Injections in Patients With Progressive Forms of Multiple Sclerosis (MS)
An open prospective study with multiple (every 6-12 months) intrathecal or intravenous injections of autologous MSC in patients with progressive forms of MS (secondary progressive, primary progressive or relapsing-progressive), who failed to respond to first and second lines of immunomodulatory treatments and deteriorated (at least 0.5 degree in the EDSS scale) during the year preceding their inclusion to our study or had at least one major relapse without sufficient recovery.
Read the detailed description
An open prospective study with multiple intrathecal or intravenous injections of autologous MSC in 24 patients with progressive forms of MS (secondary progressive, primary progressive or relapsing-progressive), who failed to respond to first and second lines of immunomodulatory treatments and deteriorated (at least 0.5 degree in the EDSS scale) during the year preceding their inclusion to our study or had at least one major relapse without sufficient recovery. Patients will be treated with 1x10 million MSC per kg of body weight, intrathecally and intravenously and subsequently with up to 8 courses of IT- or IV-injections of MSC (at the same dose), at intervals of 6-12 months. The duration of the trial is 4 years.
Patients will be followed up every 3 months for the whole duration of the trial, for safety assessment and changes in the disability scores (EDSS).
Immunological analysis will be performed at 4 time points (day 1, month 1, month 3 and month 6) following the first MSC-treatment and will include a fluorescent cell sorter (FACS) analysis to evaluate the proportions of the lymphocytes expressing markers of immune activation or of regulatory cell phenotype.
- Conditions
- Multiple Sclerosis
- Being tested
- Mesenchymal Stem Cells (MSC)
- Keywords
- Multiple Sclerosis, Mesenchymal Stem Cells
- Medical subject headings
- Multiple Sclerosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mesenchymal Stem Cells (MSC)Biological
Also called MSC
Repeated intrathecal and intravenous injection of autologous mesenchymal stem cells (1 million cells per Kg of body weight) at 6 months intervals.
| Study group | Role | What they receive |
|---|---|---|
| Repeated MSCs treatment in MS patients | Experimental | Treatment with intrathecal and intravenous injection of autologous MSC (1 million cells per Kg of body weight) Receives: Biological: Mesenchymal Stem Cells (MSC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Appearance of adverse events
To evaluate the safety and tolerability of MSCs repeated treatment in progressive MS patients
Measured: 48 months following first treatment
The changes in Expanded Disability Status Scale (EDSS) score 0-10 scale, higher scores show worsening of disability)
To evaluate the changes in Expanded Disability Status Scale (EDSS) score after repeated MSC treatments compared to run-in period.
Measured: 48 months
Secondary outcomes (4)
Changes in the percentage of CD4/CD25/FoxP3 triple positive stained cells (T regulatory cells), following MSC-treatment
The percentage of CD4/CD25/FoxP3 triple positive stained cells, will be tested in the peripheral blood mononuclear cells obtained from MSC-treated patients using a fluorescent cell sorter (FACS) at 1 day, 1, 3 and 6 months post-MSC treatment and compared to baseline (before treatment) values for each patient. The mean post treatment values will be compared to the respective pre-treatmnent values at each time point.
Measured: up to 6 months
Changes in the percentage of CD3+CD69+ cells (activated lymphocytes), following MSC-treatment
The percentage of CD3+CD69+ cells (activated lymphocytes), will be tested in the peripheral blood mononuclear cells obtained from MSC-treated patients using a fluorescent cell sorter (FACS) at 1 day, 1, 3 and 6 months post-MSC treatment and compared to baseline (before treatment) values for each patient. The mean post treatment values will be compared to the respective pre-treatmnent values at each time point.
Measured: up to 6 months
Changes in the percentage of CD11c+/CD86+/Lin- cells (dendritic cells and antigen-presenting macrophages), following MSC-treatment
The percentage of CD11c+/CD86+/Lin- cells (dendritic cells and antigen-presenting macrophages), will be tested in the peripheral blood mononuclear cells obtained from MSC-treated patients using a fluorescent cell sorter (FACS) at 1 day, 1, 3 and 6 months post-MSC treatment and compared to baseline (before treatment) values for each patient. The mean post treatment values will be compared to the respective pre-treatmnent values at each time point.
Measured: up to 6 months
Changes in the proliferation ability of mononuclear cells to PHA, following MSC-treatment
The proliferation ability of mononuclear cells to PHA will be tested in the peripheral blood mononuclear cells obtained from MSC-treated patients using a standard proliferative Thymidine-uptake assay at 1 day, 1, 3 and 6 months post-MSC treatment and compared to baseline (before treatment) values for each patient. The mean post treatment value (proliferation index) will be compared to the respective pre-treatmnent values at each time point.
Measured: up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Mar 2021
- Study start1 Jan 2013
- Primary completion1 Dec 2016
- Study completion1 Apr 2020
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 Multiple SclerosisStudies of the same condition, open and under way.
- More trials run by Hadassah Medical OrganizationThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Model description
- Single Center, Open phase study
- Masking
- None (open label)
- Enrolment
- 24 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hadassah Medical Organization
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Dimitrios Karussis, PhD, Principal investigator, Hadassah HMO
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04823000
- Sponsor's protocol ID
- MSC-MS-001
- Acronym
- MSC-pMS
- Status last verified
- Nov 2020
- First submitted
- 11 Jan 2021
- Last updated
- 30 Mar 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Petrou P, Kassis I, Ginzberg A, Halimi M, Yaghmour N, Abramsky O, Karussis D. Long-Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cell Injections in Patients With Progressive Forms of Multiple Sclerosis. Front Neurol. 2021 May 31;12:639315. doi: 10.3389/fneur.2021.639315. eCollection 2021.
PubMed 34135843
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Long Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cells (MSC) Injections in Patients With Progressive Forms of Multiple Sclerosis (MS)
- ClinicalTrials.gov ID
- NCT04823000
- Acronym / sponsor ID
- MSC-pMS / MSC-MS-001
- Conditions
- Multiple Sclerosis
- Keywords
- Multiple Sclerosis, Mesenchymal Stem Cells
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 24 participants (actual)
- Lead sponsor
- Hadassah Medical OrganizationUniversity, hospital or other
- Study start
- 1 Jan 2013 (actual)
- Primary completion
- 1 Dec 2016 (actual)
- Study completion
- 1 Apr 2020 (actual)
- First posted
- 30 Mar 2021 (actual)
- 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.
An open prospective study with multiple (every 6-12 months) intrathecal or intravenous injections of autologous MSC in patients with progressive forms of MS (secondary progressive, primary progressive or relapsing-progressive), who failed to respond to first and second lines of immunomodulatory treatments and deteriorated (at least 0.5 degree in the EDSS scale) during the year preceding their inclusion to our study or had at least one major relapse without sufficient recovery.
Detailed description
An open prospective study with multiple intrathecal or intravenous injections of autologous MSC in 24 patients with progressive forms of MS (secondary progressive, primary progressive or relapsing-progressive), who failed to respond to first and second lines of immunomodulatory treatments and deteriorated (at least 0.5 degree in the EDSS scale) during the year preceding their inclusion to our study or had at least one major relapse without sufficient recovery. Patients will be treated with 1x10 million MSC per kg of body weight, intrathecally and intravenously and subsequently with up to 8 courses of IT- or IV-injections of MSC (at the same dose), at intervals of 6-12 months. The duration of the trial is 4 years.
Patients will be followed up every 3 months for the whole duration of the trial, for safety assessment and changes in the disability scores (EDSS).
Immunological analysis will be performed at 4 time points (day 1, month 1, month 3 and month 6) following the first MSC-treatment and will include a fluorescent cell sorter (FACS) analysis to evaluate the proportions of the lymphocytes expressing markers of immune activation or of regulatory cell phenotype.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single Center, Open phase study
| Arm | Type | Receives |
|---|---|---|
| Repeated MSCs treatment in MS patients | Experimental | Biological: Mesenchymal Stem Cells (MSC)Treatment with intrathecal and intravenous injection of autologous MSC (1 million cells per Kg of body weight) |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Consenting patients fulfilling the Poser's criteria for definite MS
- Age 18-70
- Male and female
- EDSS rate 5.5-7.5 (moderate to high disability)
- Failure to two lines of the currently available registered immunomodulatory treatments for MS. The lack of response to these treatments was determined by either an increase in EDSS or the appearance of at least two relapses of MS during the year prior to inclusion.
Key exclusion criteria (4 listed)
- Patients who were treated with cytotoxic medications during the last three months prior to the infusion.
- Patients suffering from significant cardiac, renal or hepatic failure or any other disease that may risk the patient or interfere with the ability to interpret the results.
- Patients with active infections.
- Patients with cognitive decline or inability to understand and sign the informed consent.
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 |
|---|---|---|
| Mesenchymal Stem Cells (MSC)Also: MSCRepeated intrathecal and intravenous injection of autologous mesenchymal stem cells (1 million cells per Kg of body weight) at 6 months intervals. | Biological | Repeated MSCs treatment in MS patients |
Primary outcome
Appearance of adverse events
Time frame: 48 months following first treatment
To evaluate the safety and tolerability of MSCs repeated treatment in progressive MS patients
The changes in Expanded Disability Status Scale (EDSS) score 0-10 scale, higher scores show worsening of disability)
Time frame: 48 months
To evaluate the changes in Expanded Disability Status Scale (EDSS) score after repeated MSC treatments compared to run-in period.
4 secondary outcomes
Changes in the percentage of CD4/CD25/FoxP3 triple positive stained cells (T regulatory cells), following MSC-treatment
Time frame: up to 6 months
Changes in the percentage of CD3+CD69+ cells (activated lymphocytes), following MSC-treatment
Time frame: up to 6 months
Changes in the percentage of CD11c+/CD86+/Lin- cells (dendritic cells and antigen-presenting macrophages), following MSC-treatment
Time frame: up to 6 months
Changes in the proliferation ability of mononuclear cells to PHA, following MSC-treatment
Time frame: up to 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 30 Mar 2021.
- Derived from this study: PubMed 34135843Petrou P, Kassis I, Ginzberg A, Halimi M, Yaghmour N, Abramsky O, Karussis D. Long-Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cell Injections in Patients With Progressive Forms of Multiple Sclerosis. Front Neurol. 2021 May 31;12:639315. doi: 10.3389/fneur.2021.639315. eCollection 2021.
Related trials for Multiple Sclerosis
RecruitingPhase 2
Metformin as an add-on or Monotherapy in Treatment of Aging People With Multiple Sclerosis (MS)
Multiple Sclerosis
RecruitingObservational study
Pain Phenotypes in Individuals With Multiple Sclerosis
Multiple Sclerosis, Chronic Pain
Not yet recruiting
Evaluating the Effect of the Zeen Mobility Device on Clinical Practicality, Safety, and Impact (Via Assessments of Walking, Standing Tolerance, Balance, Endurance, Effort, and Participation in Daily Tasks) in an Outpatient Rehabilitation Setting for Individuals With Mobility Impairments.
Stroke, Parkinson's Disease (PD)
RecruitingPhase 3
Dalfampridine Combined With Physical Therapy for Mobility Impairment in Multiple Sclerosis
Multiple Sclerosis
RecruitingPhase 2
Targeting Agonists of Glucagon-like Peptide-1 Receptor for Multiple Sclerosis
Multiple Sclerosis
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, PhD principal investigator
Hadassah HMO
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Mesenchymal Stem Cells (MSC) in people with Multiple Sclerosis, run by Hadassah Medical Organization.
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 5 inclusion and 4 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 30 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
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?
Appearance of adverse events (time frame: 48 months following first treatment). 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 NCT04823000, 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 30 Mar 2021.