Clinical Trial: A Pilot Study of MSCs Iufusion and Etanercept to Treat Ankylosing Spondylitis

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Phase III Study of Human Bone Marrow-Derived Mesenchymal Stem Cells to Treat AS

Brief Summary: The purpose of this study is to evaluate the safety and clinical effect of mesenchymal stem cells (MSCs) derived from human bone marrow at a dose of 1.0E+6 MSC/kg in subject for the therapy of Ankylosing spondylitis (AS) and to compare the efficacy of MSCs and Etanercept to treat this disease.

Detailed Summary:

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 methotrexate, salicylazosulfapyridine 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. Although the application of TNF alpha receptor inhibitor (such as Etanercept) has got the success in the early treatment of ankylosing spondylitis, the tolerance to this biological agent make the therapy to this disease rather difficult. Recently, owning to its immunoregulatory, immunosuppressive, stimulating hematopoiesis and tissue repairing properties, the infusion of human MSCs isolated from human bone marrow have been a promising and effective treatment to AS patients. This study will evaluate the safety and effectiveness of MSC transplantation in the AS patients and compare the efficiency with the Etanercept to treat AS patients.

This study will last 2 to 3 years. Participants will be randomly assigned to receive either MSC transplant therapy (experimental group) or Etanercept therapy (control group
Sponsor: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Current Primary Outcome: The Assessment of Spondyloarthritis International Society (ASAS)20 response [ Time Frame: 48 weeks ]

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 absolute 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.


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • BASDAI score comparing to baseline [ Time Frame: 48 weeks ]
  • BASFI score comparing to baseline [ Time Frame: 48 weeks ]
    the Bath Ankylosing Spondylitis Functional Index
  • Imageology [ Time Frame: 48 weeks ]

    The bone marrow of the whole spine (from C2 to S1) can be detected by Magnetic resonance imaging (MRI) scan. The MRI sequence included a T1-weighted turbo spin-echo (TSE) sequence and a fat-saturated short tau inversion recovery (STIR) sequence.

    MR images were first analyzed using the ASspiMRI-a scoring system , which is based on grading disease activity on a scale of 0 to 6. In addition to the ASspiMRI-a scoring system, the inflammation area and average intensityof each inflammatory site were calculated. The background value (BV) was obtained by taking 10 normal sites of the vertebral body of 1 layer and calculating the average. The inflammation extent of each inflammatory site was calculated by the formula:

    value of inflammation area (VIA) × [value of average intensity (VAI) - BV]. The summation of the inflammation extent of all inflammatory sites in all scanning layers was defined as the total inflammation extent (TIE) of each patient.

  • C-reactive protein (CRP) [ Time Frame: 12 weeks ]
  • Erythrocyte sedimentation rate (ESR) [ Time Frame: 12 weeks ]
  • Tumor necrosis factor alpha (TNF-α) [ Time Frame: 12 weeks ]
  • Interleukin 6 (IL-6) [ Time Frame: 12 weeks ]
  • Interleukin 17 (IL-17) [ Time Frame: 12 weeks ]


Original Secondary Outcome: Same as current

Information By: Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University

Dates:
Date Received: June 16, 2016
Date Started: June 2016
Date Completion: December 2018
Last Updated: June 22, 2016
Last Verified: June 2016