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Effects of Repeated Mesenchymal Stem Cells (MSC) in Patients With Progressive Multiple Sclerosis (MSC-pMS)

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ClinicalTrials.gov Identifier: NCT04823000
Recruitment Status : Completed
First Posted : March 30, 2021
Last Update Posted : March 30, 2021
Sponsor:
Information provided by (Responsible Party):
Hadassah Medical Organization

Brief 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 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.

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Biological: Mesenchymal Stem Cells (MSC) Phase 1 Phase 2

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 24 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Intervention Model Description: Single Center, Open phase study
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Long Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cells (MSC) Injections in Patients With Progressive Forms of Multiple Sclerosis (MS)
Actual Study Start Date : January 1, 2013
Actual Primary Completion Date : December 1, 2016
Actual Study Completion Date : April 1, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Repeated MSCs treatment in MS patients
Treatment with intrathecal and intravenous injection of autologous MSC (1 million cells per Kg of body weight)
Biological: Mesenchymal Stem Cells (MSC)
Repeated intrathecal and intravenous injection of autologous mesenchymal stem cells (1 million cells per Kg of body weight) at 6 months intervals.
Other Name: MSC




Primary Outcome Measures :
  1. 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

  2. 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.


Secondary Outcome Measures :
  1. Changes in the percentage of CD4/CD25/FoxP3 triple positive stained cells (T regulatory cells), following MSC-treatment [ Time Frame: up to 6 months ]
    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.

  2. Changes in the percentage of CD3+CD69+ cells (activated lymphocytes), following MSC-treatment [ Time Frame: up to 6 months ]
    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.

  3. Changes in the percentage of CD11c+/CD86+/Lin- cells (dendritic cells and antigen-presenting macrophages), following MSC-treatment [ Time Frame: up to 6 months ]
    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.

  4. Changes in the proliferation ability of mononuclear cells to PHA, following MSC-treatment [ Time Frame: up to 6 months ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Consenting patients fulfilling the Poser's criteria for definite MS
  2. Age 18-70
  3. Male and female
  4. EDSS rate 5.5-7.5 (moderate to high disability)
  5. 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.

Exclusion Criteria:

  1. Patients who were treated with cytotoxic medications during the last three months prior to the infusion.
  2. 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.
  3. Patients with active infections.
  4. Patients with cognitive decline or inability to understand and sign the informed consent.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04823000


Sponsors and Collaborators
Hadassah Medical Organization
Investigators
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Principal Investigator: Dimitrios Karussis, PhD Hadassah HMO
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Hadassah Medical Organization
ClinicalTrials.gov Identifier: NCT04823000    
Other Study ID Numbers: MSC-MS-001
First Posted: March 30, 2021    Key Record Dates
Last Update Posted: March 30, 2021
Last Verified: November 2020

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hadassah Medical Organization:
Multiple Sclerosis
Mesenchymal Stem Cells
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases