Atorvastatin for Microvascular Endothelial Function and Raynaud in Early Diffuse Scleroderma

NCT02370784 | Completed Phase 2 Results DMC

• 2 other identifiers: PRO140101701R21AR066305-01A1
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 1

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.

Conditions

Scleroderma

Keywords

early diffuse scleroderma; Raynaud

Outcome Measures

Primary Outcomes (1)

• Proportion of Patients Improving Their EndoPAT Reactive Hyperemia Index (RHI) at the End-of-study (16 Weeks)

  EndoPAT is a proprietary device that assesses digital (microvascular) endothelial function during reactive hyperemia. A probe is placed on both index fingers. After 5 minutes of baseline observation, one arm is occluded for 5 minutes, while the other is not and serves as control. Output is the reactive hyperemia index (RHI), calculated as the post-to-pre occlusion signal ratio in the occluded side, "normalized to the control side and further corrected for baseline vascular tone" per Itamar Medical. There are no units. RHI ≤ 1.67 is abnormal and indicates endothelial dysfunction.

  Change in RHI from baseline to 16 weeks expressed as the percentage of patients who improve (respond).

Secondary Outcomes (3)

• Change in the Raynaud Condition Score (RCS) at 16 Weeks (End-of-study) From Baseline

  change in RCS from baseline to week 16

• The Median Change in the Raynaud Phenomenon Visual Analog Scale (RP-VAS) Score at 16 Weeks (End-of-study) Compared to Baseline in the Atorvastatin and Placebo Groups.

  baseline to 16 weeks

• % of Patients Who Improved Their Brachial Flow-mediation Dilation (%FMD) at 16 Weeks

  baseline to 16 weeks

Study Arms (2)

Active Drug

ACTIVE COMPARATOR

atorvastatin 40 mg once daily for sixteen weeks

Drug: atorvastatin

Placebo control

PLACEBO COMPARATOR

receive a placebo of similar appearance once daily for sixteen weeks

Drug: Placebo

Interventions

atorvastatin DRUG

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

Also known as: Lipitor

Active Drug

Placebo DRUG

oral drug of similar appearance to atorvastatin

Placebo control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Robyn T. Domsic, MD, MPH: lead
• National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS): collaborator

Study Sites (1)

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

MeSH Terms

Conditions

Scleroderma, Diffuse

Interventions

Atorvastatin

Condition Hierarchy (Ancestors)

Scleroderma, Systemic; Connective Tissue Diseases; Skin and Connective Tissue Diseases; Skin Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heptanoic Acids; Fatty Acids; Lipids

Limitations and Caveats

This was a single-centered trial, and underpowered, as only 24 were enrolled with an initial goal of 30. The groups were unbalanced for both the primary and secondary endpoint at baseline despite randomization.

Results Point of Contact

• Title: Robyn T. Domsic, MD MPH
• Organization: University of Pittsburgh School of Medicine

rtd4@pitt.edu

412-383-8000

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, MPH

Study Record Dates

• First Submitted: January 26, 2015
• First Posted: February 25, 2015
• Study Start: February 1, 2015
• Primary Completion: December 15, 2018
• Study Completion: December 15, 2019
• Last Updated: August 12, 2020
• Results First Posted: August 12, 2020

Record last verified: 2020-08

Locations

US (1)