Allogeneic Mesenchymal Stem Cells Transplantation for Systemic Sclerosis (SSc)

• Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Information provided by: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School

Tracking Information

• First Submitted Date: August 19, 2009
• First Posted Date: August 20, 2009
• Last Update Posted Date: August 20, 2009
• Study Start Date: August 2009
• Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: August 19, 2009): mRSS score,HRQOL score, SF-36 score for SSc patients [ Time Frame: monthly ]
• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: August 19, 2009)

• Remission for organ function, VC, DLCO, PAP, serum albumin, serum creatitin, weight loss, 24h proteinuria [ Time Frame: every three month ]
• SSc Serology(ATA,ACA,ANA,anti-ssDNA,anti-dsDNA,IgM,IgG,and IgA,complement C3 and C4 [ Time Frame: every three month ]
• Change of peripheral blood B and T cells [ Time Frame: every three month ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Allogeneic Mesenchymal Stem Cells Transplantation for Systemic Sclerosis (SSc)
• Official Title: Not Provided
• 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

• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Systemic Sclerosis
• Mesenchymal Stem Cells

Intervention

Biological: Allogeneic Mesenchymal Stem Cells (AlloMSC)

Allogeneic mesenchymal stem cells will be infused intravenously (single dose, 10^6 cells/kg body weight).

• Study Arms: Not Provided

Publications *

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Recruitment Information

• Recruitment Status: Unknown status
• Estimated Enrollment (submitted: August 19, 2009): 20
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2011
• Estimated Primary Completion Date: December 2010 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 15 Years to 65 Years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: China

Administrative Information

• NCT Number: NCT00962923
• Other Study ID Numbers: NJGLYY003
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: the Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Study Sponsor: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
• Verification Date: August 2009