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Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma (TAMER)

This study is currently recruiting participants.
Verified July 2017 by Robyn T. Domsic, MD, MPH, University of Pittsburgh
Sponsor:
ClinicalTrials.gov Identifier:
NCT02370784
First Posted: February 25, 2015
Last Update Posted: July 21, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
Robyn T. Domsic, MD, MPH, University of Pittsburgh
  Purpose

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.


Condition Intervention Phase
Scleroderma Drug: atorvastatin Drug: Placebo Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Robyn T. Domsic, MD, MPH, University of Pittsburgh:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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.


Estimated Enrollment: 30
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)
Arms Assigned Interventions
Active Comparator: Active Drug
atorvastatin 40 mg once daily for sixteen weeks
Drug: atorvastatin
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
Drug: Placebo
oral drug of similar appearance to atorvastatin

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

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02370784


Locations
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Dana Ivanco    412-648-7040    des2@pitt.edu   
Contact: Maureen Laffoon    412-648-5037    laffoonm@pitt.edu   
Principal Investigator: Robyn T Domsic, MD, MPH         
Sponsors and Collaborators
Robyn T. Domsic, MD, MPH
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
  More Information

Responsible Party: Robyn T. Domsic, MD, MPH, MD, MPH, University of Pittsburgh
ClinicalTrials.gov Identifier: NCT02370784     History of Changes
Other Study ID Numbers: PRO14010170
1R21AR066305-01A1 ( U.S. NIH Grant/Contract )
First Submitted: January 26, 2015
First Posted: February 25, 2015
Last Update Posted: July 21, 2017
Last Verified: July 2017

Keywords provided by Robyn T. Domsic, MD, MPH, University of Pittsburgh:
early diffuse scleroderma
Raynaud

Additional relevant MeSH terms:
Scleroderma, Systemic
Scleroderma, Diffuse
Scleroderma, Localized
Connective Tissue Diseases
Skin Diseases
Atorvastatin Calcium
Anticholesteremic Agents
Hypolipidemic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Enzyme Inhibitors