Evaluation of Stem Cell Therapy Effects on the Immune Response in Rheumatoid Arthritis Patients

Rheumatoid Arthritis Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03333681
• Other study ID #: 931523
• Secondary ID: 122
• Status: Completed
• Phase: Phase 1
• Start date: June 20, 2016
• Est. completion date: September 15, 2018

Study information

• Verified date: March 2019
• Source: Mashhad University of Medical Sciences
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

1. Objectives: Evaluation of mesenchymal stem cell therapy effects on cellular and humoral immune responses in refractory rheumatoid arthritis (RA) patients.

2. Design: This study has been performed as a phase 1 clinical trial.

3. 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.

4. 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.

5. Intervention: A single dose of intravenous autologous bone marrow derived mesenchymal stem cells have been administered into patients with resistance to non-biological DMARDs.

6. 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: September 15, 2018
• Est. primary completion date: August 15, 2018
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 35 Years to 60 Years

Eligibility

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.

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Biological:
• Autologous mesenchymal stem cells
A single intravenous administration of autologous bone marrow derived mesenchymal stem cells(1000000 to 2000000 cells/Kg)

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Mashhad University of Medical Sciences

References & Publications (3)

Álvaro-Gracia JM, Jover JA, García-Vicuña R, Carreño L, Alonso A, Marsal S, Blanco F, Martínez-Taboada VM, Taylor P, Martín-Martín C, DelaRosa O, Tagarro I, Díaz-González 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	At 0 and 6 months follow up