Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma

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.

Inclusion Criteria:

1. early diffuse scleroderma (< 3 years from the first scleroderma-related symptom)

2. Raynaud phenomenon

3. no use of lipid-lowering medication within 60 days

Exclusion Criteria:

1. pregnancy

2. renal or kidney dysfunction (creatinine < 2.0 mg/dL or creatinine clearance < 60
c/min)

3. diabetes mellitus

4. known cardiovascular disease or a prior history of stroke

5. history of liver disease

6. new or changed dose of calcium channel blockers (CCB) and angiotensin receptor
blockers (ARBs) in the last 4 weeks

7. known allergy or adverse reaction to the atorvastatin or another statin drug