Clinical trial NCT00962923: Allogeneic Mesenchymal Stem Cells Transplantation for Systemic Sclerosis (SSc)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Systemic Sclerosis
Mesenchymal Stem Cells
Keywords: Systemic sclerosis
Mesenchymal Stem Cells
Transplantation
Lead sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Sponsor class: OTHER
First posted: 2009-08-20
Enrollment: 20
Sex: ALL
Minimum age (years): 15
Maximum age (years): 65
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This study will explore safety and efficacy of allogeneic mesenchymal stem cells transplantation (MSCT) to treat patients with diagnosis of systemic sclerosis(SSc) who have been resistant to multiple standard treatments. The underlying hypothesis is that the SSc condition is caused by an abnormal immune homeostasis that can be restored by MSCT.

Detailed description: * To test a new approach using allogeneic derived mesenchymal stem cell based therapy (MSCT) to treat refractory SSc
* To determine the disease-free survival in SSc patients treated with MSCT
* To assess adverse events of allogeneic MSC transplantation
* To assess the association of remission for organ function, clinical score and SSc serology levels at baseline with disease-free survival

Eligibility criteria: Inclusion Criteria:

* All patients fulfilled the American College of Rheumatology (former American Rheumatism Association - ARA) for SSc
* Rapidly progressive disease \<2 years duration with a modified Rodnan skin score(mRSS) above 20, plus ESR \>25 mm/first h and/or Hb \<11 g/dL, not explained by other causes than active SSc
* lung involvement: with a vital capacity (VC) or DLCO below 70% predicted, or a mean pulmonary artery pressure (PAP) above 40 mmHg (measured by echocardiography)
* digestive tract involvement: with serum albumin ,25 g/L or weight loss exceeding 10% body weight in the preceding year
* kidney involvement: with 24-h urinary protein above 0.5 g or serum creatinine above 120 mmol/L

Exclusion Criteria:

* Uncontrolled arrhythmia, echocardiographic left ventricular ejection fraction (LVEF) \<50% or mean PAP \>50 mmHg, DLCO\<45% of predicted
* Creatinine clearance \<20 ml/min
* Platelets\<80 000/mm3, haemorrhagic cystitis
* (4) HIV or HTLV1 seropositivity, malignancy, pregnancy, a cardiac or vascular prosthesis, and no vascular access

Primary outcomes:
measure: mRSS score,HRQOL score, SF-36 score for SSc patients
timeFrame: monthly
Secondary outcomes:
measure: Remission for organ function, VC, DLCO, PAP, serum albumin, serum creatitin, weight loss, 24h proteinuria
timeFrame: every three month
measure: SSc Serology(ATA,ACA,ANA,anti-ssDNA,anti-dsDNA,IgM,IgG,and IgA,complement C3 and C4
timeFrame: every three month
measure: Change of peripheral blood B and T cells
timeFrame: every three month
Other outcomes:
Locations:
city: Nanjing
country: China
facility: the Affiliated Drum Tower Hospital of Nanjing University Medical School
state: Jiangsu
Study officials:
References:
citation: Sun L, Akiyama K, Zhang H, Yamaza T, Hou Y, Zhao S, Xu T, Le A, Shi S. Mesenchymal stem cell transplantation reverses multiorgan dysfunction in systemic lupus erythematosus mice and humans. Stem Cells. 2009 Jun;27(6):1421-32. doi: 10.1002/stem.68.
citation: Liang J, Zhang H, Hua B, Wang H, Wang J, Han Z, Sun L. Allogeneic mesenchymal stem cells transplantation in treatment of multiple sclerosis. Mult Scler. 2009 May;15(5):644-6. doi: 10.1177/1352458509104590.
citation: Zhou K, Zhang H, Jin O, Feng X, Yao G, Hou Y, Sun L. Transplantation of human bone marrow mesenchymal stem cell ameliorates the autoimmune pathogenesis in MRL/lpr mice. Cell Mol Immunol. 2008 Dec;5(6):417-24. doi: 10.1038/cmi.2008.52.
citation: Sun LY, Zhang HY, Feng XB, Hou YY, Lu LW, Fan LM. Abnormality of bone marrow-derived mesenchymal stem cells in patients with systemic lupus erythematosus. Lupus. 2007;16(2):121-8. doi: 10.1177/0961203306075793.
citation: Zhang H, Liang J, Tang X, Wang D, Feng X, Wang F, Hua B, Wang H, Sun L. Sustained benefit from combined plasmapheresis and allogeneic mesenchymal stem cells transplantation therapy in systemic sclerosis. Arthritis Res Ther. 2017 Jul 19;19(1):165. doi: 10.1186/s13075-017-1373-2.
citation: Akiyama K, Chen C, Wang D, Xu X, Qu C, Yamaza T, Cai T, Chen W, Sun L, Shi S. Mesenchymal-stem-cell-induced immunoregulation involves FAS-ligand-/FAS-mediated T cell apoptosis. Cell Stem Cell. 2012 May 4;10(5):544-55. doi: 10.1016/j.stem.2012.03.007. Epub 2012 Apr 26.