Clinical trial NCT03333681: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Rheumatoid Arthritis
Keywords: Rheumatoid arthritis
Stem Cells
Cellular immunity
Humoral immunity
chemokines
homing of immune cells
Lead sponsor: Mashhad University of Medical Sciences
Sponsor class: OTHER
First posted: 2017-11-07
Enrollment: 15
Sex: FEMALE
Minimum age (years): 35
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

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.

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.

Primary outcomes:
measure: Effect of mesenchymal stem cells therapy on the percentage of regulatory T cells
timeFrame: At 0 and 6 months follow up
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Mashhad University of Medical Sciences
name: Mojgan Mohammadi, Ph.D
role: PRINCIPAL_INVESTIGATOR
References:
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.
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.
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.