Evaluation of Stem Cell Therapy Effects on the Immune Response in Rheumatoid Arthritis Patients
Primary Purpose
Rheumatoid Arthritis
Status
Completed
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
Autologous mesenchymal stem cells
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring Rheumatoid arthritis, Stem Cells, Cellular immunity, Humoral immunity, chemokines, homing of immune cells
Eligibility Criteria
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 age 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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Refractory rheumatoid arthritis patients
Arm Description
Autologous mesenchymal stem cells
Outcomes
Primary Outcome Measures
Effect of mesenchymal stem cells therapy on the percentage of regulatory T cells
Percentage change in regulatory T cells from baseline which is analysed by fluorescence-activated cell sorting (FACS)
Secondary Outcome Measures
Full Information
NCT ID
NCT03333681
First Posted
September 14, 2017
Last Updated
March 12, 2019
Sponsor
Mashhad University of Medical Sciences
1. Study Identification
Unique Protocol Identification Number
NCT03333681
Brief Title
Evaluation of Stem Cell Therapy Effects on the Immune Response in Rheumatoid Arthritis Patients
Official Title
Evaluation of Mesenchymal Stem Cell Therapy Effects on the Cellular and Humoral Immune Responses and Additionally Study on the Effect of Chemokines in Homing of the Immune Cells in Refractory Rheumatoid Arthritis Patients
Study Type
Interventional
2. Study Status
Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
June 20, 2016 (Actual)
Primary Completion Date
August 15, 2018 (Actual)
Study Completion Date
September 15, 2018 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mashhad University of Medical Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
Objectives: Evaluation of mesenchymal stem cell therapy effects on cellular and humoral immune responses in refractory rheumatoid arthritis (RA) patients.
Design: This study has been performed as a phase 1 clinical trial.
Setting and conduct: Autologous bone marrow derived mesenchymal stem cells were obtained by bone marrow aspiration and cultured in Minimum Essential Medium-Alpha (MEM-alpha) for 4 weeks in standard clean room and then transfused to RA patients intravenously.
Participant's major eligibility criteria is as follows: Ten refractory rheumatoid arthritis patients who show resistance to non biological Disease-modifying antirheumatic drugs (DMARDs) after 6 to 12 months have been enrolled in this study.
Intervention: A single dose of intravenous autologous bone marrow derived mesenchymal stem cells have been administered into patients with resistance to non-biological DMARDs.
Main outcome measures (variables): Finding of mesenchymal stem cell therapy effects on the cellular and humoral immune responses and evaluation of the effect of chemokines in homing of immune cells following the intervention.
Detailed Description
Refractory rheumatoid arthritis patients who met the inclusion/exclusion criteria have been selected. After signing informed consent form, autologous stem cells were obtained by bone marrow aspiration. Isolation and culture (3 to 4 weeks in MEM-alpha medium) of mesenchymal stem cells (MSCs) were performed in accredited good manufacturing practices (GMP) clean room. A panel of cluster of differentiation (CD) markers including CD105, CD166, CD44, CD45, CD90, and CD34 were checked for making sure about differentiation of cells into MSCs after 3-4 weeks of cell culture. Viability of MSCs was checked by Trypan blue testing and all of the cultivations were negative for bacterial contamination. A single dose of 1000000 to 2000000 mesenchymal stem cells/kg infused into patients intravenously. To prevent anaphylactic reactions, a single intravenous dose of hydrocortison (100 ml) and oral dimenhydrinate (10 ml) were administered before MSCs infusion into patients. The effects of mesenchymal stem cells on the cellular and humoral immune responses and also the role of chemokines in homing of immune cells were studied at time points 1, 6 and 12 months after intravenous administration of MSCs in refractory rheumatoid arthritis.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Rheumatoid arthritis, Stem Cells, Cellular immunity, Humoral immunity, chemokines, homing of immune cells
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Refractory rheumatoid arthritis patients
Arm Type
Experimental
Arm Description
Autologous mesenchymal stem cells
Intervention Type
Biological
Intervention Name(s)
Autologous mesenchymal stem cells
Intervention Description
A single intravenous administration of autologous bone marrow derived mesenchymal stem cells(1000000 to 2000000 cells/Kg)
Primary Outcome Measure Information:
Title
Effect of mesenchymal stem cells therapy on the percentage of regulatory T cells
Description
Percentage change in regulatory T cells from baseline which is analysed by fluorescence-activated cell sorting (FACS)
Time Frame
At 0 and 6 months follow up
10. Eligibility
Sex
Female
Gender Based
Yes
Minimum Age & Unit of Time
35 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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 age 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Mojgan Mohammadi, Ph.D
Organizational Affiliation
Mashhad University of Medical Sciences
Official's Role
Principal Investigator
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
PubMed Identifier
27269294
Citation
Alvaro-Gracia JM, Jover JA, Garcia-Vicuna R, Carreno L, Alonso A, Marsal S, Blanco F, Martinez-Taboada VM, Taylor P, Martin-Martin C, DelaRosa O, Tagarro I, Diaz-Gonzalez F. Intravenous administration of expanded allogeneic adipose-derived mesenchymal stem cells in refractory rheumatoid arthritis (Cx611): results of a multicentre, dose escalation, randomised, single-blind, placebo-controlled phase Ib/IIa clinical trial. Ann Rheum Dis. 2017 Jan;76(1):196-202. doi: 10.1136/annrheumdis-2015-208918. Epub 2016 Jun 7.
Results Reference
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PubMed Identifier
21837432
Citation
Liang J, Li X, Zhang H, Wang D, Feng X, Wang H, Hua B, Liu B, Sun L. Allogeneic mesenchymal stem cells transplantation in patients with refractory RA. Clin Rheumatol. 2012 Jan;31(1):157-61. doi: 10.1007/s10067-011-1816-0. Epub 2011 Aug 12.
Results Reference
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PubMed Identifier
23941289
Citation
Wang L, Wang L, Cong X, Liu G, Zhou J, Bai B, Li Y, Bai W, Li M, Ji H, Zhu D, Wu M, Liu Y. Human umbilical cord mesenchymal stem cell therapy for patients with active rheumatoid arthritis: safety and efficacy. Stem Cells Dev. 2013 Dec 15;22(24):3192-202. doi: 10.1089/scd.2013.0023. Epub 2013 Oct 4.
Results Reference
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Evaluation of Stem Cell Therapy Effects on the Immune Response in Rheumatoid Arthritis Patients
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