The Safety and Effects of Mesenchymal Stem Cell (MSCs) in the Treatment of Rheumatoid Arthritis

The Effects and Safety of Mesenchymal Stem Cells in the Treatment of Moderate/Severe Rheumatoid Arthritis， a Multicenter Randomized Controlled Clinical Study

This study evaluates the safety and therapeutic effects of single-dose human umbilical cord blood mesenchymal stem cells (UC-MSCs) on the adult patients with moderate/severe Rheumatoid Arthritis accompany with anemia or/and Interstitial pulmonary disease. Half of participants will receive UC-MSCs and keep the present medication,while the other half will receive a placebo and keep the present medication.

Study Overview

• Status: Unknown
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Biological: UC-MSCs

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ping Zhu, Doctor; Phone Number: 86-29-84773951; Email: zhuping@fmmu.edu.cn

Study Locations

• China
  • Shaanxi
    • Xi'an, Shaanxi, China, 710032
      • Recruiting
      • Xijing Hospital
      • Contact: Ping Zhu; Phone Number: 862984773951 862984773951; Email: zhuping@fmmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Fulfill 2010 ACR/ the European League Against Rheumatism (EULAR) classification criteria or the 1987 ACR classification criteria.
2. Age limits:18 to 70 years old.
3. Freely given informed consent.
4. Disease Activity Score (DAS) 28≥3.2或 Simple Disease Activity Index (SDAI)>11.0或 Clinical Disease Activity Index (CDAI) >10.0.
5. Hemoglobin < 90 g/L and/or interstitial lung disease shown in high resolution CT.
6. Poor response to current treatment. The current treatment refers to receive the medicines (including Leflunomide, Methotrexate, Sulphasalazine, Hydroxychloroquine, Cyclosporine A,and Tacrolimus, alone or in combination ) for 3 months, and maintain the stable-dose of drugs for at least 1 month.
7. More than 3 months and a stable dose for at least 1 month are required if glucocorticoid is used. The dose of glucocorticoid is less than or equal to10mg/ day of prednisone.

Exclusion Criteria:

1. Participants who received glucocorticoid therapy by intra-articular injection within 1 week.
2. Glucocorticoid that participants received is more than 10 mg/day of prednisone within 1 months.
3. Complication with other connective tissue disease (except for Sjogren syndrome) .
4. Participants with chronic and acute infection (bacteria, virus and parasite,etc.).
5. Participants with acute and chronic tuberculosis infection.
6. Malignant tumors or participants with a family history of malignant tumors.
7. Participants have a family history of allergic conditions.
8. Participants infected by Hepatitis B Virus(HBV), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus （HIV）.
9. Participants suffer from central nervous system demyelinating disease or multiple sclerosis (MS) currently or in the past.
10. Participants received live vaccines with 3 months.
11. Drug abuse and alcoholism.
12. Participants with severe mental or neurological disorders that affect informed consent and/or the presentation or observer of adverse events.
13. Participants with pregnant or in breast-feeding, and patients who has a pregnancy plan within 1 year.
14. Participants received stem cell therapy in the past.
15. Participants received any biological agents within 3 months.
16. Anemia (such as anemia with dysplasia) and interstitial lung disease for other reasons.
17. Participants with cardiovascular and cerebrovascular damage, such as thrombosis.
18. Participants taking drugs that affect the test for blood and lung.
19. Participants taking any traditional Chinese medicine.
20. Participants taking immune modulators such as Transfer Factor, Thymosin and Intravenous Immunoglobulin (IVIG), and so on.
21. Other cases that participants are considered by investigator that they did not meet the requirements for enrollment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: UC-MSCs treatment; the participants will receive the single-dose UC-MSCs (1×10^6 cells/kg ) in combined with the present treatment.	Biological: UC-MSCs; The UC-MSCs will be administrated by intravenous injection at the dose of 1×10^6 cells/kg.; Other Names: placebo
No Intervention: no UC-MSCs treatment; the participants will receive the placebo in combined with the present treatment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement rate of blood routine hemoglobin (HGB) compared to baseline.	The HGB increases by 10g compared to the baseline is considered improvement.	24 weeks
Improvement rate of forced vital capacity (FVC) and/or carbon monoxide diffusing capacity (DLCO) compared to baseline.	FVC increases by 0.5% and DLCO increases by 10% compared to baseline are considered improvement.	24 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The remission rates of American College of Rheumatology (ACR) 20, ACR 50 and ACR 70.	The patients achieves 20%, 50%, or 70% remission according to American College of Rheumatology (ACR) criteria.	12 weeks and 24 weeks
White blood cell count and platelet count improved compared to the baseline.	White blood cell count increases to the 3.5×10^9/L and platelet count increases to 80×10^ 9.	12 weeks and 24 weeks
Improvement rate of blood routine hemoglobin (HGB) compared to baseline.	The HGB increases by 10 g compared to the baseline is considered improvement.	12 weeks
Improvement rate of forced vital capacity (FVC) and/or carbon monoxide	FVC increases by 0.5% and DLCO increases by 10% compared to baseline	12 weeks
Image improvement of lung on high resolution CT.	The area change of image of lung.	24 weeks
Improvement of 6-minute walking distance compared to baseline.		12 weeks and 24 weeks

Collaborators and Investigators

• Sponsor: Xijing Hospital
• Collaborators: Changhai Hospital; Southwest Hospital, China

Study record dates

Study Major Dates

• Study Start (Actual): December 26, 2017
• Primary Completion (Anticipated): December 31, 2019
• Study Completion (Anticipated): June 30, 2020

Study Registration Dates

• First Submitted: January 7, 2019
• First Submitted That Met QC Criteria: January 7, 2019
• First Posted (Actual): January 9, 2019

Study Record Updates

• Last Update Posted (Actual): January 9, 2019
• Last Update Submitted That Met QC Criteria: January 7, 2019
• Last Verified: December 1, 2018

More Information

Terms related to this study

• Keywords: anemia; Interstitial pulmonary disease
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: 2014ZX09508002

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No