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

Phase 1

Completed

• Conditions: Rheumatoid Arthritis
• Interventions: Biological: Autologous mesenchymal stem cells

• Registration Number: NCT03333681
• Lead Sponsor: Mashhad University of Medical Sciences

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.

Study Timeline

• Study Start: 2016-06-20
• Study First Submitted: 2017-09-14
• Study First Submitted QC: 2017-11-03
• Study First Posted: 2017-11-07
• Primary Completion: 2018-08-15
• Study Completion: 2018-09-15
• Status Verified: 2019-03
• Last Update Submitted: 2019-03-12
• Last Update Posted: 2019-03-13

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 15

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Refractory rheumatoid arthritis patients	Autologous mesenchymal stem cells	Autologous mesenchymal stem cells

Primary Outcome Measures

Name	Time	Method
Effect of mesenchymal stem cells therapy on the percentage of regulatory T cells	At 0 and 6 months follow up	Percentage change in regulatory T cells from baseline which is analysed by fluorescence-activated cell sorting (FACS)