Phase II Study of Umbilical Cord/Placenta-Derived Mesenchymal Stem Cells to Treat AS
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Ankylosing Spondylitis
- Sponsor
- Shandong University
- Enrollment
- 10
- Locations
- 1
- Primary Endpoint
- The Assessment of Spondyloarthritis International Society (ASAS)20 response
- Last Updated
- 14 years ago
Overview
Brief Summary
The purpose of this study is to evaluate the safety and efficacy of mesenchymal stem cells (MSCs) derived from human umbilical cord/placenta at a dose of 1.0E+6 MSC/kg in subject for the therapy of Ankylosing spondylitis (AS)
Detailed Description
Ankylosing spondylitis (AS) is a chronic, progressive inflammatory rheumatic disease involving primarily the sacroiliac joints and the axial skeleton. The main clinical features are back pain and progressive stiffness of the spine. Oligoarthritis of the hips and shoulders, enthesopathy, and anterior uveitis are common, and involvement of the heart and lungs is rare. The current understanding of the pathogenesis of this disorder is limited.It mainly about to hereditary susceptibility (eg hla-b27),infection and autoimmunity. Although traditional drugs, such as Nonsteroidal antiinflammatory drugs (NSAIDs) disease-modifying antirheumatic drugs (DMARDs such as MTX,SASP OR thalidomide) and steroids have been used in the treatment of AS, however, many studies have indicated that the overall response to these drugs is not satisfied. Addition, the severe side effects of these drugs have also been observed. The management of AS patients therefore remains unsatisfactory and targeted therapies are needed. Human MSCs isolated from human umbilical cord/placenta have been shown to have immunoregulatory, immunosuppressive, stimulating hematopoiesis and tissue repairing properties. This study will evaluate the safety and effectiveness of MSC transplantation in the AS patients. This study will last 2 to 3 years. Participants will be randomly assigned to receive either MSC transplant +DMARDs therapy (experimental group) or DMARDs therapy (control group). Patients will undergo MSC transplant at the start of the study on Day 0. After 3 months, patients will receive the second MSC transplantation. After six and twelve months from the first transplantation, patients will be evaluated.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Patient age 18\~60 years old with plan to infuse MSCs.
- •Diagnosis of "Definite AS" (arthritis of the spine) as defined by the modified New York criteria
- •Stable doses of sulfasalazine,methotrexate,thalidomide,hydroxychloroquine, low-dose corticosteroids, and NSAIDs are permitted
- •Patients must have an ECOG 0\~
- •No moderate or sever organ dysfunction: Ejection fraction\>45%; Creatinine \<176 umol/L.
- •No severe infection.
- •Each patient must sign written informed consent.
Exclusion Criteria
- •Other serious concomitant diseases (uncontrolled/severe kidney, liver, haematological, gastrointestinal, endocrine, cardiovascular, pulmonary, neurological or cerebral disease)
- •Psychiatric condition that would limit informed consent.
- •HIV, hepatitis B or C, tuberculosis, other infections
- •Positive Pregnancy Test or lactation
- •Patient has enrolled another clinical trial study within last 4 weeks.
- •Contraindications to MSC
Outcomes
Primary Outcomes
The Assessment of Spondyloarthritis International Society (ASAS)20 response
Time Frame: 1 year
ASAS measures symptomatic improvement in AS patients.ASAS=4 domains:patient global assessment of disease activity,pain,function,inflammation.ASAS 20=20% improvement(vs.baseline)and an abosolute change≥1 units on a 0-10 scale(0=no disease activity;10=high disease activity)for ≥3 domains,and no worsening in remaining domain. Patient global Pain Function (as measured by the Bath Ankylosing Spondylitis Functional Index - BASFI) Inflammation (mean of the Bath Ankylosing Spondylitis Disease Activity Index - BASDAI question 5 and 6)
erythrocyte sedimentation rate (ESR)
Time Frame: 1 year
erythrocyte sedimentation rate (ESR) level will be mainly observed after transplanting 3, 6,12-month.
imageology
Time Frame: 1 year
imageology will be mainly observed after transplanting 3, 6,12-month.
C-reactive protein (CRP)
Time Frame: 1 year
C-reactive protein (CRP) level will be mainly observed after transplanting 3, 6,12-month.
Secondary Outcomes
- Percentage of systemic T regulatory cell population(1 year)
- Side effects(1 year)