Study 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 suggests 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 aspects of SSc pathogenesis. A few preliminary statin studies have found conflicting results, but have used patients with overall longstanding disease, when the vasculopathy may have not been amenable to treatment.

In the preliminary work the study team has found evidence that statins may mediate microvascular endothelial dysfunction in patients with very early systemic sclerosis. Laser speckle contrast imaging (LSCI) is a newer imaging modality that assesses microcirculation and has been proposed as a surrogate marker for systemic microvascular function. The preliminary data showed a distinct pattern of microcirculatory flow as measured by LSCI compared to healthy age, gender, and race-matched controls and holds promise as a functional assessment of microvascular function in SSc patients. The study team hypothesizes that treatment with atorvastatin in a well-defined cohort of early diffuse SSc will improve microvascular endothelial function as measured by EndoPAT and thereby improve related Raynaud symptoms. The study proposes to apply LSCI imaging as a modality to assess microvascular endothelial function response to statins and hypothesizes that this modality will allow to predict responders to statins.

ELIGIBILITY CRITERIA:

Ages Eligible for Study:           18 Years to 70 Years   (Adult, Older Adult)

Sexes Eligible for Study:          All

Accepts Healthy Volunteers:  No

Inclusion Criteria:

• early diffuse scleroderma (< 3 years from the first scleroderma-related symptom)
• Raynaud phenomenon
• no use of lipid-lowering medication within 60 days

Exclusion Criteria:

• pregnancy
• renal or kidney dysfunction (creatinine < 2.0 mg/dL or creatinine clearance < 60 c/min)
• diabetes mellitus
• known cardiovascular disease or a prior history of stroke
• history of liver disease
• new or changed dose of calcium channel blockers (CCB) and angiotensin receptor blockers (ARBs) in the last 4 weeks
• known allergy or adverse reaction to the atorvastatin or another statin drug

Study Design:

Allocation: Randomized

Intervention Model: Parallel Assignment

Masking: Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose: Treatment

Study Location(s):

University of Pittsburgh, Pittsburgh, Pennsylvania, United States, 15261

Study Website:

https://clinicaltrials.gov/ct2/show/NCT02370784?term=NCT02370784&rank=1