Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma

NCT ID: NCT02370784

Last Updated: 2020-08-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 24 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-02-28
• Study Completion Date: 2019-12-15

Brief 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.

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.

Conditions

Scleroderma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Active Drug

atorvastatin 40 mg once daily for sixteen weeks

Group Type: ACTIVE_COMPARATOR

atorvastatin

Intervention Type: DRUG

Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.

Placebo control

receive a placebo of similar appearance once daily for sixteen weeks

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

oral drug of similar appearance to atorvastatin

Interventions

atorvastatin

Atorvastatin is an oral cholesterol-lowering medication commonly referred to as statin therapy.

Intervention Type: DRUG

Placebo

oral drug of similar appearance to atorvastatin

Intervention Type: DRUG

Other Intervention Names

Lipitor

Eligibility 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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

Robyn T. Domsic, MD, MPH

OTHER

Sponsor Role: lead

Responsible Party

Robyn T. Domsic, MD, MPH

MD, MPH

Responsibility Role: SPONSOR_INVESTIGATOR

Locations

University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

1R21AR066305-01A1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PRO14010170

Identifier Type: -

Identifier Source: org_study_id