NCT00433186

Mycophenolate Mofetil in Systemic Sclerosis

Phase I, Open-label Study of Mycophenolate Mofetil In Systemic Sclerosis

• Status: Completed
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 30 (estimated)
• Sponsor: Boston University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This is a research study of an investigational product called Mycophenolate mofetil (MMF). The study is designed to establish the safety and potential benefit of MMF. MMF has proven one of the most effective medications to date for SLE and associated nephritis. It also appears to be active in polymyositis and dermatomyositis. This medication inhibits inosine monophosphate dehydrogenase, the rate-limiting enzyme in synthesis of guanosine nucleotides. It blocks the type II isoform found in activated lymphocytes more potently than the type I isoform inhibiting both T- and B-lymphocytes. In SSc, MMF has been tried after anti-thymocyte globulin in one small open label study with efficacy with a significant improvement in skin score. We will test the safety and efficacy of MMF in SSc. All study patients will receive the study medication. The effect of the study medication will be examined in two subgroups of patients: those with early or progressive skin disease (skin substudy) and those with muscle disease (muscle substudy). The change in modified Rodnan skin score (MRSS) and creatinine phosphokinase (CK) for, respectively, the skin and muscle substudies at 6 months after treatment will be compared to baseline values.

Detailed description

Systemic sclerosis (SSc) is an autoimmune/connective tissue disease with complex pathogenesis involving immune system dysregulation, leading to fibrosis. Inflammatory and autoimmune aspects of this disease overlap systemic lupus erythematosus (SLE), a disease shown clearly to respond to MMF. Activated T-cells, the probable target of MMF in SLE, likely also play an important role in SSc pathogenesis. Evidence for this includes the similarity of SSc skin disease to chronic graft versus host disease, a disease in which T-cells play a critical role. MMF has proven one of the most effective medications to date for SLE and associated nephritis \[1\]. It also appears to be active in polymyositis and dermatomyositis, disease that also show significant overlap with SSc \[2\]. Myositis can also be a feature of SSc, suggesting that his disease manifestation might be particularly likely to respond to MMF. MMF inhibits inosine monophosphate dehydrogenase, the rate-limiting enzyme in synthesis of guanosine nucleotides. It blocks the type II isoform found in activated lymphocytes more potently than the type I isoform inhibiting both T- and B-lymphocytes \[3\]. In SSc, mycophenolate has been tried after anti-thymocyte globulin in one small open label study with efficacy with a significant improvement in skin score \[4\]. However, MMF has not been tried alone inSSc and has not been tried in muscle disease associated with SSc. In this study, we will test the safety and efficacy of MMF in SSc. In this study all study patients will receive the medication.

Conditions

• Diffuse Cutaneous Systemic Sclerosis

Interventions

Type	Name	Description
DRUG	Mycophenolate Mofetil	Mycophenolate 3000 mg each day

Timeline

• Start date: 2006-03-01
• Primary completion: 2011-03-01
• Completion: 2011-03-01
• First posted: 2007-02-09
• Last updated: 2011-03-31

Locations

1 site across 1 country: United States