Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma
Information source: University of Pittsburgh
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Scleroderma
Intervention: atorvastatin (Drug); Placebo (Drug)
Phase: Phase 2
Status: Recruiting
Sponsored by: University of Pittsburgh
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.
Clinical Details
Official title: The Effect of Atorvastatin on Microvascular Endothelial Function and Raynaud in Early Diffuse Systemic Sclerosis
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: effect of atorvastatin therapy on change in microvascular endothelial function by Noninvasive vascular testing.
Secondary outcome: effect of atorvastatin on change in Raynaud symptoms measured by a patient reported questionnaire.effect of atorvastatin on change in microcirculatory flow by Noninvasive vascular testing. effect of atorvastatin on change in macrovascular endothelial function by using Noninvasive vascular testing.
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.
Eligibility
Minimum age: 18 Years.
Maximum age: 70 Years.
Gender(s): Both.
Criteria:
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
Locations and Contacts
University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States; Recruiting Dana Ivanco, Phone: 412-648-7040, Email: des2@pitt.edu Maureen Laffoon, Phone: 412-648-5037, Email: laffoonm@pitt.edu Robyn T Domsic, MD, MPH, Principal Investigator
Additional Information
Starting date: February 2015
Last updated: March 3, 2015
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