Protocol summary
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Study aim
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Evaluation of mesenchymal stem cell therapy effects on cellular immune response in refractory rheumatoid arthritis patients.
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Design
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This study is a single-arm clinical trial in which a single intravenous dose of autologous bone marrow derived mesenchymal stem cells will be administred to 21 patinets with refractory rheumatoid arthritis.
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Settings and conduct
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Autologous bone marrow derived mesenchymal stem cells will be obtained by bone marrow aspiration and will be cultured in Minimum Essential Medium-Alpha for 4 weeks in standard clean room and then transfused to RA patients intravenously.
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Participants/Inclusion and exclusion criteria
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Twenty one refractory rheumatoid arthritis patients who show resistance to non biological DMARDs after 6 to 12 months will be enrolled in this study. Non-resistant RA patients to non-biological DMARDs will not be enrolled in this study.
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Intervention groups
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A single intravenous administration of autologous bone marrow derived mesenchymal stem cells (2000000 to 3000000 cells/Kg) to refractory rheumatoid arthritis patients with resistance to non-biological DMARDs
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Main outcome variables
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Finding of mesenchymal stem cell therapy effects on the cellular immune responses.
General information
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Reason for update
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To correct the ethics committee reference number.
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Acronym
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IRCT registration information
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IRCT registration number:
IRCT2015102824760N1
Registration date:
2016-06-12, 1395/03/23
Registration timing:
prospective
Last update:
2023-08-12, 1402/05/21
Update count:
2
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Registration date
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2016-06-12, 1395/03/23
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Registrant information
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Recruitment status
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Recruitment complete
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Funding source
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Research Chancellor, Mashhad University of Medical Sciences
Council for Stem Cell Sciences and Technologies, Presidency of the Islamic Republic of Iran, Vice presidency for Science and Technology
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Expected recruitment start date
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2016-06-19, 1395/03/30
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Expected recruitment end date
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2018-06-20, 1397/03/30
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Actual recruitment start date
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empty
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Actual recruitment end date
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empty
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Trial completion date
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empty
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Scientific title
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Evaluation of Mesenchymal stem cell therapy effects on the cellular immune response in refractory rheumatoid arthritis patients
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Public title
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Evaluation of Mesenchymal stem cell therapy effects on the cellular immune response in refractory rheumatoid arthritis patients
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Purpose
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Treatment
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Inclusion/Exclusion criteria
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Inclusion criteria:
Resistant RA patients to non-biological DMARDs
Treated RA patients by non-biological drugs
Treated RA patients by Prednisolone, Hydroxychloroquine, Sulfasalazine and Methotrexate
Patients aged between 35-60 years
Refractory RA patients with no other rheumatologic disorders and inflammatory diseases
Exclusion criteria:
Non-resistant RA patients to non-biological DMARDs
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Age
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From 35 years old to 60 years old
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Gender
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Both
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Phase
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1
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Groups that have been masked
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No information
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Sample size
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Target sample size:
21
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Randomization (investigator's opinion)
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N/A
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Randomization description
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Blinding (investigator's opinion)
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Not blinded
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Blinding description
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Placebo
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Not used
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Assignment
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Single
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Other design features
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Ethics committees
1
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Ethics committee
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Approval date
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2015-11-21, 1394/08/30
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Ethics committee reference number
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IR.MUMS.REC.1394.529
2
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Ethics committee
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Approval date
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2023-05-20, 1402/02/30
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Ethics committee reference number
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IR.MUMS.REC.1402.076
Health conditions studied
1
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Description of health condition studied
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Rheumatoid arthritis
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ICD-10 code
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M05
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ICD-10 code description
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Diseases of the musculoskeletal system and connective tissue
Primary outcomes
1
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Description
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Interleukin-1
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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pg/ml using ELISA assay
2
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Description
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TNF-alpha
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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pg/ml using ELISA assay
3
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Description
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Interleukin-4
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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pg/ml using ELISA assay
4
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Description
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Interleukin-10
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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pg/ml using ELISA assay
5
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Description
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TGF-beta
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Frequency and the intensity of stained cells in the ELISPOT assay
6
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Description
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Interleukin-17
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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pg/ml using ELISA assay
7
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Description
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T-bet transcription factor
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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The copy number of desired gene using RT-PCR assay
8
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Description
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GATA3 transcription factor
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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The copy number of desired gene using RT-PCR assay
9
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Description
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FOXP3 transcription factor
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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The copy number of desired gene using RT-PCR assay
10
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Description
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ROR-gamma T transcription factor
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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The copy number of desired gene using RT-PCR assay
11
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Description
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T helper cells
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Frequency of desired cells using flow cytometry technique
12
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Description
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Regulatory T cells
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Frequency of desired cells using flow cytometry technique
13
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Description
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Th17
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Frequency of desired cells using flow cytometry technique
14
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Description
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Disease activity score (DAS)
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Clinical and laboratory findings
15
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Description
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Visual analogue scale (VAS)
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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The amount of pain that a patient feels
16
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Description
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Erythrocyte sedimentation rate(ESR)
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Erythrocyte sedimentation rate in millimeters
17
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Description
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C-reactive protein (CRP)
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Latex agglutination test
18
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Description
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Rheumatoid factor(RF)
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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Latex agglutination test
19
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Description
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Anti-cyclic citrullinated peptide (anti-CCP)
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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ELISA test
20
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Description
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TNF-α
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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The copy number of desired gene using RT-PCR assay
21
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Description
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IL-17A
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Timepoint
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Before intervention and after 1, 6, 12 months follow up
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Method of measurement
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The copy number of desired gene using RT-PCR assay
Secondary outcomes
1
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Description
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Anaphylaxis
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Timepoint
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After IV infusion of MSCs
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Method of measurement
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Clinical manifestations, hypotension and hypoglycemia
2
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Description
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Differentiation of MSCs to unwanted cells
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Timepoint
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After IV infusion of MSCs
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Method of measurement
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Clinical manifestations
Intervention groups
1
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Description
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A single intravenous administration of autologous bone marrow derived mesenchymal stem cells(2000000 to 3000000 cells/Kg).
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Category
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Treatment - Other
1
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Sponsor
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Grant name
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Grant code / Reference number
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931523
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Research Chancellor, Mashhad University of Medical Sciences
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Proportion provided by this source
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75
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Academic
2
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Sponsor
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Grant name
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Grant code / Reference number
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122
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Is the source of funding the same sponsor organization/entity?
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Yes
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Title of funding source
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Council for Stem Cell Sciences and Technologies, Presidency of the Islamic Republic of Iran, Vice pr
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Proportion provided by this source
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25
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Public or private sector
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Public
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Domestic or foreign origin
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Domestic
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Category of foreign source of funding
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empty
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Country of origin
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Type of organization providing the funding
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Other
Sharing plan
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Deidentified Individual Participant Data Set (IPD)
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Undecided - It is not yet known if there will be a plan to make this available
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Study Protocol
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Undecided - It is not yet known if there will be a plan to make this available
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Statistical Analysis Plan
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Undecided - It is not yet known if there will be a plan to make this available
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Informed Consent Form
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Undecided - It is not yet known if there will be a plan to make this available
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Clinical Study Report
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Undecided - It is not yet known if there will be a plan to make this available
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Analytic Code
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Undecided - It is not yet known if there will be a plan to make this available
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Data Dictionary
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Undecided - It is not yet known if there will be a plan to make this available