Clinical trial NCT06360861: Evaluate the Safety and Feasibility of Allogeneic Mesenchymal Stem Cells in Patients With Multiple Sclerosis
Official title: An Open-label, Non-randomized, Phase I Study of Allogeneic Placenta Derived Mesenchymal Stem Cells in Patients With Secondary-Progressive Multiple Sclerosis (SPMS),
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Multiple Sclerosis
Secondary-Progressive Multiple Sclerosis
Mesenchymal Stem Cells
Keywords: Mesenchymal Stem cells
Multiple Sclerosis
Placenta derived Mesenchymal Stem Cells
Stem Cell therapy
Neuroimmunology
Autoimmune Disease
Lead sponsor: Tehran University of Medical Sciences
Sponsor class: OTHER
First posted: 2024-04-11
Enrollment: 5
Sex: ALL
Minimum age (years): 17
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Open-label phase 1, single-center, pre-post comparison study
Primary purpose: TREATMENT

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.

Eligibility 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.

Primary outcomes:
measure: Number of participants with Treatment-Emergent Adverse Events [Safety and Tolerability].
timeFrame: Up to 6 months
Secondary outcomes:
measure: Number of participants with a change in disability as measured by Expanded Disability Status Scale .
timeFrame: Up to 6 months
measure: Number of participants with a change in cognitive function as measured by the Paced Auditory Serial Addition Test .
timeFrame: Up to 6 months
measure: Number of participants with a change in cognitive performance as measured by Persian version of minimal assessment of cognitive function in MS battery.
timeFrame: Up to 6 months
measure: Number of participants with a change in brain connectivity as measured by Functional magnetic resonance imaging .
timeFrame: Up to 6 months
measure: Number of participants with a change in white matter integrity as measured by quantitative diffusion tensor imaging .
timeFrame: Up to 6 months
measure: Number of participants with a change in processing and motor speed as assessed by the Symbol Digit Modalities Test .
timeFrame: Up to 6 months
measure: Number of participants with evaluation of verbal learning and memory deficits as measured by the California Verbal Learning Test second edition .
timeFrame: Up to 6 months
measure: Proportion of patients with change in CD20 / CD19 B cells surface markers
timeFrame: Up to 3 months
measure: Biological Assessments including IL-10, IL-6, IL-17, and TNFα levels of cytokines.
timeFrame: Up to 3 months
measure: Proportion of patients with change in T2 lesion volume on brain MRI.
timeFrame: Up to 6 months
measure: Proportion of patients with change in brain volume on MRI.
timeFrame: Up to 6 months
measure: Proportion of patients for assessment of visuospatial learning as measured by the Brief Visuospatial Memory Test-Revised .
timeFrame: Up to 6 months
measure: Proportion of patients for assessment of visuospatial ability as measured by Judgment of Line Orientation Test .
timeFrame: Up to 6 months
measure: Proportion of patients for evaluation of executive functions as measured by the Delis-Kaplan Executive Function System Sorting and descriptive tests.
timeFrame: Up to 6 months
measure: Proportion of patients for measuring verbal fluency as measured by the Controlled Oral Word Association Test .
timeFrame: Up to 6 months
measure: Proportion of patients for psychological assessment as measured by the validated Persian version of Symptom Checklist-90-Revised .
timeFrame: Up to 6 months
measure: Proportion of patients for evaluation of fatigue as measured by was examined by the Persian version of Fatigue Severity Scale .
timeFrame: Up to 6 months
measure: Proportion of patients for assessment of visuospatial ability as measured by the brief visuospatial memory test-revised test.
timeFrame: Up to 6 months
measure: Proportion of patients for assessment of visuospatial ability as measured by the California Verbal Learning Test Second Edition test.
timeFrame: Up to 6 months
Other outcomes:
Locations:
city: Tehran
country: Iran, Islamic Republic of
facility: Tehran University of Medical Sciences,Tehran, Iran
Study officials:
affiliation: Multiple Sclerosis Research Center,Neuroscience Institute,Sina Hospital,Tehran, Iran.
name: Abdorreza Naser Moghadasi, MD
role: STUDY_DIRECTOR
affiliation: Research Institute for Oncology, Hematology& Cell Therapy Facility, Shariati Hospital ,Tehran, Iran.
name: Mohsen Nikbakht, PhD
role: STUDY_DIRECTOR
affiliation: Applied Cell Sciences,Tehran University of Medical Sciences,Tehran, Iran.
name: Ameneh Shokati, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Shokati A, Naser Moghadasi A, Nikbakht M, Sahraian MA, Mousavi SA, Ai J. A focus on allogeneic mesenchymal stromal cells as a versatile therapeutic tool for treating multiple sclerosis. Stem Cell Res Ther. 2021 Jul 13;12(1):400. doi: 10.1186/s13287-021-02477-5.
citation: Ebrahimi-Barough S, Ai J, Payab M, Alavi-Moghadam S, Shokati A, Aghayan HR, Larijani B, Arjmand B. Standard Operating Procedure for the Good Manufacturing Practice-Compliant Production of Human Endometrial Stem Cells for Multiple Sclerosis. Methods Mol Biol. 2021;2286:199-212. doi: 10.1007/7651_2020_281.