Clinical trial NCT04823000: Effects of Repeated Mesenchymal Stem Cells (MSC) in Patients With Progressive Multiple Sclerosis
Official title: Long Term Clinical and Immunological Effects of Repeated Mesenchymal Stem Cells (MSC) Injections in Patients With Progressive Forms of Multiple Sclerosis (MS)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis
Mesenchymal Stem Cells
Lead sponsor: Hadassah Medical Organization
Sponsor class: OTHER
First posted: 2021-03-30
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Single Center, Open phase study
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: Appearance of adverse events
timeFrame: 48 months following first treatment
measure: The changes in Expanded Disability Status Scale (EDSS) score 0-10 scale, higher scores show worsening of disability)
timeFrame: 48 months
Secondary outcomes:
measure: Changes in the percentage of CD4/CD25/FoxP3 triple positive stained cells (T regulatory cells), following MSC-treatment
timeFrame: up to 6 months
measure: Changes in the percentage of CD3+CD69+ cells (activated lymphocytes), following MSC-treatment
timeFrame: up to 6 months
measure: Changes in the percentage of CD11c+/CD86+/Lin- cells (dendritic cells and antigen-presenting macrophages), following MSC-treatment
timeFrame: up to 6 months
measure: Changes in the proliferation ability of mononuclear cells to PHA, following MSC-treatment
timeFrame: up to 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Hadassah HMO
name: Dimitrios Karussis, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.