Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma
Condition: Scleroderma
MeSH terms: Scleroderma, Systemic; Scleroderma, Diffuse
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to learn about the effect atorvastatin on blood vessel function
      and Raynaud symptoms in patients with early diffuse systemic sclerosis.

      Systemic sclerosis is a disease characterized by blood vessel injury, immune system
      activation and fibrosis. Blood vessel injury is thought to be important early in the disease.
      Blood vessel complications of systemic sclerosis include Raynaud phenomena, finger and toe
      ulcers, and pulmonary hypertension. While atorvastatin reduces cholesterol, it is recognized
      to have many effects beyond cholesterol reduction. These include improvement of blood vessel
      function and reduction of fibrosis. We hypothesize that treatment with atorvastatin over 16
      weeks will improve blood vessel function and Raynaud symptom in patients with early diffuse
      systemic sclerosis. We hope that by targeting therapy early in the disease we may delay blood
      vessel changes and improve Raynaud symptoms.
    

Detailed description: 
      Systemic sclerosis (SSc) is a multisystem autoimmune illness characterized by vasculopathy,
      immune system activation and fibrosis of the skin and internal organs. SSc affects
      approximately 240 people per million in the US, but is a disease for which there is no FDA
      approved medication. Current hypothesis of pathogenesis suggest that a vascular injury with
      endothelial dysfunction may be an inciting event contributing to immunologic activation and
      fibrosis in the pathogenesis of the disease. More than 90% of individuals with SSc have
      vascular complications including Raynaud phenomenon, digital ulcers or gangrene and pulmonary
      hypertension; with microvascular abnormalities felt to contribute to Raynaud and digital
      ulcerations.

      Statin medications are well-recognized to have pleiotropic effects which may modify all three
      aspects of SSc pathogenesis. Early diagnosis and treatment of microvascular endothelial
      dysfunction and Raynaud phenomeonan may have the greatest effect in early disease. Thus, we
      hypothesize that treatment with atorvastatin in a well-defined cohort of early diffuse
      systemic sclerosis will produce beneficial results.

      Participants will be patients with early diffuse systemic sclerosis and Raynaud phenomenon
      who have no history of cardiovascular disease or diabetes. A total of 30 patients will be
      enrolled and followed for 16 weeks. Half the patients will be randomized to atorvastatin and
      half to placebo. Patients will be allowed to continue underlying immunosuppressive and
      Raynaud therapy at stable doses during the trial. Since this is a pilot study, future larger
      controlled trials will be necessary to clearly demonstrate drug effectiveness. Investigators
      are hoping that this study will give us signals to guide a future multicenter clinical trial.
    

Intervention name(s): atorvastatin; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.; oral drug of similar appearance to atorvastatin
Other intervention name(s): Lipitor
Intervention MeSH terms: Atorvastatin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: early diffuse scleroderma; Raynaud