Mesenchymal Stem Cells, Multiple Sclerosis, Secondary-Progressive Multiple Sclerosis
Conditions
Keywords
Mesenchymal Stem cells, Multiple Sclerosis, Placenta derived Mesenchymal Stem Cells, Stem Cell therapy, Neuroimmunology, Autoimmune Disease
Brief summary
To assess the safety and of a single dose of IV infusion of placenta derived Mesenchymal Stem Cells (PLMSCs) in patients with secondary progressive Multiple Sclerosis (SPMS) disease. Monitoring will be encompassed baseline assessments and follow-ups over subsequent months, evaluating clinical signs, Expanded Disability Status Scale (EDSS), cytokines, diffusion tensor imaging (DTI), functional MRI (fMRI), cognitive & psychological evaluations, and flow cytometry for B cell markers.
Detailed description
This open-label phase I study will be conducted in MS Clinic of Sina and Shariati Hospital of Tehran province . In this study, diagnosis and management of MS patients will be performed based on McDonald's criteria and Iran's diagnostic and treatment protocols. The patients will be received a single injection of PLMSCs through the intravenous cannula. The proposed study will assess safety and short efficacy endpoints of PLMSCs administered to 5 patients with SPMS. The primary objective of the trial is freedom from treatment associated adverse events at 1,3 and 6 months' post treatment. Secondary objective will be efficacy as assessed at baseline, at 1,3 and 6 months and will be based on the following: EDSS, cytokines, DTI, fMRI, cognitive & psychological evaluations, and flow cytometry for B cell markers.
Interventions
BIOLOGICALAllogenic placenta derived mesenchymal stem cells
Allogenic placenta derived mesenchymal stem cells, 3 million cells/kg body weight via intravenous injection.
Sponsors
Tehran University of Medical Sciences
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Open-label phase 1, single-center, pre-post comparison study
Eligibility
Sex/Gender
ALL
Age
17 Years to 45 Years
Healthy volunteers
No
Inclusion criteria
Criteria: Inclusion Criteria: * Age between 17-45 years Patients with SPMS . * Must be able to Sign informed consent . * Currently taking Rituximab. * Disease duration of more than 2 and less than 16 years.
Exclusion criteria
* Pregnancy or breastfeeding. * hepatitis B and C, human immunodeficiency virus (HIV), and human T-cell lymphotropic virus (HTLV) disease. * Using cytotoxic agents within 3 months prior to the study. * Severe anemia (hemoglobin\< 8 mg/dl), coagulation disorders. * history of malignancy . * liver disorders . * significant cardiac, renal or hepatic failure . * Active or chronic infection. * Life-threatening organ dysfunction. * Unable to give written informed consent . * Current treatment with an investigational therapy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with Treatment-Emergent Adverse Events [Safety and Tolerability]. | Up to 6 months | adverse events |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of participants with a change in disability as measured by Expanded Disability Status Scale . | Up to 6 months | Proportion of patients with clinical improvement in EDSS score compared to baseline. EDSS scores range from 0 = no disability to 10 = death due to MS and higher scores mean a worse outcome. |
| Number of participants with a change in cognitive function as measured by the Paced Auditory Serial Addition Test . | Up to 6 months | The minimum score is 0 and maximum score is 60, and higher scores mean a better outcome. |
| Number of participants with a change in cognitive performance as measured by Persian version of minimal assessment of cognitive function in MS battery. | Up to 6 months | Assessment of cognitive function |
| Number of participants with a change in brain connectivity as measured by Functional magnetic resonance imaging . | Up to 6 months | Assessment of brain connectivity |
| Number of participants with a change in white matter integrity as measured by quantitative diffusion tensor imaging . | Up to 6 months | Change from baseline in white matter integrity |
| Number of participants with a change in processing and motor speed as assessed by the Symbol Digit Modalities Test . | Up to 6 months | Change from baseline in processing and motor speed of patients and higher scores mean a better outcome. |
| Number of participants with evaluation of verbal learning and memory deficits as measured by the California Verbal Learning Test second edition . | Up to 6 months | Change from baseline in verbal learning and memory deficits and higher scores mean a better outcome. |
| Proportion of patients with change in CD20 / CD19 B cells surface markers | Up to 3 months | Blood samples will be collected pre and post treatment for immediate or ulterior analysis. |
| Biological Assessments including IL-10, IL-6, IL-17, and TNFα levels of cytokines. | Up to 3 months | Blood samples will be collected pre and post treatment for immediate or ulterior analysis. |
| Proportion of patients for measuring verbal fluency as measured by the Controlled Oral Word Association Test . | Up to 6 months | Change from baseline in measuring verbal fluency |
| Proportion of patients with change in brain volume on MRI. | Up to 6 months | Change from baseline in brain volume |
| Proportion of patients for assessment of visuospatial learning as measured by the Brief Visuospatial Memory Test-Revised . | Up to 6 months | Change from baseline in visuospatial learning |
| Proportion of patients for assessment of visuospatial ability as measured by Judgment of Line Orientation Test . | Up to 6 months | Change from baseline in visuospatial ability |
| Proportion of patients for evaluation of executive functions as measured by the Delis-Kaplan Executive Function System Sorting and descriptive tests. | Up to 6 months | Change from baseline in executive functions |
| Proportion of patients for psychological assessment as measured by the validated Persian version of Symptom Checklist-90-Revised . | Up to 6 months | Symptom Checklist-90(SCL-90) is a collection of nine subscales (with 90 items) for evaluation of Somatization, Obsessive-compulsive, interpersonal sensitivity, depression, anxiety, hostility, phobic anxiety, paranoid ideation, and psychoticism in the past week. Each item has a 5-point Likert scale and scoring from 0 to 4. SCL-90 Global Severity was calculated by dividing the sum of all subscales scores by 9. |
| Proportion of patients for evaluation of fatigue as measured by was examined by the Persian version of Fatigue Severity Scale . | Up to 6 months | Fatigue Severity Scale(FSS )is a scale with 9 items, which assesses the fatigue severity in the past 2 weeks. Each item has a score from 1 to 7 and total score will be from 9 to 63. Higher FSS score indicates higher fatigue severity. |
| Proportion of patients for assessment of visuospatial ability as measured by the brief visuospatial memory test-revised test. | Up to 6 months | Change from baseline in visuospatial ability |
| Proportion of patients for assessment of visuospatial ability as measured by the California Verbal Learning Test Second Edition test. | Up to 6 months | Change from baseline in visuospatial ability |
| Proportion of patients with change in T2 lesion volume on brain MRI. | Up to 6 months | Change from baseline in T2 lesion volume. |
Countries
Iran
Outcome results
None listed