Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma (TAMER)
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.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||The Effect of Atorvastatin on Microvascular Endothelial Function and Raynaud in Early Diffuse Systemic Sclerosis|
- effect of atorvastatin therapy on change in microvascular endothelial function by Noninvasive vascular testing. [ Time Frame: baseline and 16 weeks ]Noninvasive vascular testing will be used to assess endothelial function using EndoPAT technology.
- effect of atorvastatin on change in Raynaud symptoms measured by a patient reported questionnaire. [ Time Frame: baseline and 16 weeks ]Raynaud Condition Score, Raynaud visual analog scale (VAS) and digital ulcer VAS
- effect of atorvastatin on change in microcirculatory flow by Noninvasive vascular testing. [ Time Frame: baseline and 16 weeks ]Noninvasive vascular testing using laser speckle contrast imaging of the hand.
- effect of atorvastatin on change in macrovascular endothelial function by using Noninvasive vascular testing. [ Time Frame: baseline and 16 weeks ]Noninvasive vascular testing using brachial flow-mediated dilation.
|Study Start Date:||February 2015|
|Estimated Study Completion Date:||February 2018|
|Estimated Primary Completion Date:||August 2017 (Final data collection date for primary outcome measure)|
Active Comparator: Active Drug
atorvastatin 40 mg once daily for sixteen weeks
Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.
Other Name: Lipitor
Placebo Comparator: Placebo control
receive a placebo of similar appearance once daily for sixteen weeks
oral drug of similar appearance to atorvastatin
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02370784
|United States, Pennsylvania|
|University of Pittsburgh||Recruiting|
|Pittsburgh, Pennsylvania, United States, 15261|
|Contact: Dana Ivanco 412-648-7040 email@example.com|
|Contact: Maureen Laffoon 412-648-5037 firstname.lastname@example.org|
|Principal Investigator: Robyn T Domsic, MD, MPH|