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

Multiple Sclerosis Clinical Trial

— MSC-pMS  

Official title:

Long Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cells (MSC) Injections in Patients With Progressive Forms of Multiple Sclerosis (MS)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04823000
• Other study ID #: MSC-MS-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: January 1, 2013
• Est. completion date: April 1, 2020

Study information

• Verified date: November 2020
• Source: Hadassah Medical Organization
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 24
• Est. completion date: April 1, 2020
• Est. primary completion date: December 1, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Multiple Sclerosis
• Sclerosis

Intervention

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.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Hadassah Medical Organization

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Appearance of adverse events	To evaluate the safety and tolerability of MSCs repeated treatment in progressive MS patients	48 months following first treatment
Primary	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.	48 months
Secondary	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.	up to 6 months
Secondary	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.	up to 6 months
Secondary	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.	up to 6 months
Secondary	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.	up to 6 months