Evaluate the Safety and Feasibility of Allogeneic Mesenchymal Stem Cells in Patients With Multiple Sclerosis (MS)

An Open-label, Non-randomized, Phase I Study of Allogeneic Placenta Derived Mesenchymal Stem Cells in Patients With Secondary-Progressive Multiple Sclerosis (SPMS),

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.

Study Overview

• Status: Completed
• Conditions: Multiple Sclerosis; Mesenchymal Stem Cells; Secondary-Progressive Multiple Sclerosis
• Intervention / Treatment: Biological: Allogenic placenta derived mesenchymal stem cells

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.

• Study Type: Interventional
• Enrollment (Actual): 5
• Phase: Phase 1

Contacts and Locations

Study Locations

• Iran, Islamic Republic of
  • Tehran, Iran, Islamic Republic of
    • Tehran University of Medical Sciences,Tehran, Iran

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Placenta derived mesenchymal cells; Allogenic placenta derived mesenchymal stem cells, 3 million cells/kg body weight via intravenous injection	Biological: Allogenic placenta derived mesenchymal stem cells; Allogenic placenta derived mesenchymal stem cells, 3 million cells/kg body weight via intravenous injection.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with Treatment-Emergent Adverse Events [Safety and Tolerability].	adverse events	Up to 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants with a change in disability as measured by Expanded Disability Status Scale .	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.	Up to 6 months
Number of participants with a change in cognitive function as measured by the Paced Auditory Serial Addition Test .	The minimum score is 0 and maximum score is 60, and higher scores mean a better outcome.	Up to 6 months
Number of participants with a change in cognitive performance as measured by Persian version of minimal assessment of cognitive function in MS battery.	Assessment of cognitive function	Up to 6 months
Number of participants with a change in brain connectivity as measured by Functional magnetic resonance imaging .	Assessment of brain connectivity	Up to 6 months
Number of participants with a change in white matter integrity as measured by quantitative diffusion tensor imaging .	Change from baseline in white matter integrity	Up to 6 months
Number of participants with a change in processing and motor speed as assessed by the Symbol Digit Modalities Test .	Change from baseline in processing and motor speed of patients and higher scores mean a better outcome.	Up to 6 months
Number of participants with evaluation of verbal learning and memory deficits as measured by the California Verbal Learning Test second edition .	Change from baseline in verbal learning and memory deficits and higher scores mean a better outcome.	Up to 6 months
Proportion of patients with change in CD20 / CD19 B cells surface markers	Blood samples will be collected pre and post treatment for immediate or ulterior analysis.	Up to 3 months
Biological Assessments including IL-10, IL-6, IL-17, and TNFα levels of cytokines.	Blood samples will be collected pre and post treatment for immediate or ulterior analysis.	Up to 3 months
Proportion of patients with change in T2 lesion volume on brain MRI.	Change from baseline in T2 lesion volume.	Up to 6 months
Proportion of patients with change in brain volume on MRI.	Change from baseline in brain volume	Up to 6 months
Proportion of patients for assessment of visuospatial learning as measured by the Brief Visuospatial Memory Test-Revised .	Change from baseline in visuospatial learning	Up to 6 months
Proportion of patients for assessment of visuospatial ability as measured by Judgment of Line Orientation Test .	Change from baseline in visuospatial ability	Up to 6 months
Proportion of patients for evaluation of executive functions as measured by the Delis-Kaplan Executive Function System Sorting and descriptive tests.	Change from baseline in executive functions	Up to 6 months
Proportion of patients for measuring verbal fluency as measured by the Controlled Oral Word Association Test .	Change from baseline in measuring verbal fluency	Up to 6 months
Proportion of patients for psychological assessment as measured by the validated Persian version of Symptom Checklist-90-Revised .	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.	Up to 6 months
Proportion of patients for evaluation of fatigue as measured by was examined by the Persian version of Fatigue Severity Scale .	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.	Up to 6 months
Proportion of patients for assessment of visuospatial ability as measured by the brief visuospatial memory test-revised test.	Change from baseline in visuospatial ability	Up to 6 months
Proportion of patients for assessment of visuospatial ability as measured by the California Verbal Learning Test Second Edition test.	Change from baseline in visuospatial ability	Up to 6 months

Collaborators and Investigators

• Sponsor: Tehran University of Medical Sciences
• Investigators: Study Director: Abdorreza Naser Moghadasi, MD, Multiple Sclerosis Research Center,Neuroscience Institute,Sina Hospital,Tehran, Iran.; Study Director: Mohsen Nikbakht, PhD, Research Institute for Oncology, Hematology& Cell Therapy Facility, Shariati Hospital ,Tehran, Iran.; Principal Investigator: Ameneh Shokati, PhD, Applied Cell Sciences,Tehran University of Medical Sciences,Tehran, Iran.

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): July 23, 2019
• Primary Completion (Actual): March 4, 2024
• Study Completion (Actual): March 6, 2024

Study Registration Dates

• First Submitted: March 17, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): April 11, 2024
• Last Update Submitted That Met QC Criteria: April 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Neuroimmunology; Autoimmune Disease; Mesenchymal Stem cells; Stem Cell therapy; Placenta derived Mesenchymal Stem Cells
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Neoplasms; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Disease Attributes; Neoplastic Processes; Chronic Disease; Multiple Sclerosis; Multiple Sclerosis, Chronic Progressive; Sclerosis; Neoplasm Metastasis
• Other Study ID Numbers: 1400-1-233-51589; IR.TUMS.MEDICINE.REC.1400.197 (Other Grant/Funding Number: Tehran University of Medical Sciences)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No