SystemIc iNflammation and Microvascular diSease PreventIon in psoRiatic diseasE (INSPIRE)

This is a single-label open-arm mechanistic clinical study recruiting patients with psoriasis or psoriatic arthritis with elevated cardiovascular risk. Subjects enrolled in this study will receive statin treatment with rosuvastatin. The statin treatment in this study will be used as an intervention with widely known pleiotropic CV risk reduction effects, including anti-inflammatory reduction. Subjects will be studied before statin therapy and followed for 48 weeks on treatment. The primary outcome will be change in the coronary flow reserve (CFR) as measured by cardiac PET. Overall, this study will examine the impact of statin therapy on changes in CFR as a reflection of impaired coronary vasoreactivity and a manifestation of myocardial ischemia, which may precede clinical CV events (and visible changes in plaque morphology) in high-risk patients with psoriatic disease.

Study Overview

• Status: Withdrawn
• Conditions: Psoriasis; Psoriatic Arthritis; Cardiovascular Risk Factor
• Intervention / Treatment: Drug: Rosuvastatin

Detailed Description

The primary objective of this study is to investigate the impact of maximally tolerated statin (MTS) therapy on coronary flow reserve (CFR), reflecting coronary vasoreactivity and myocardial tissue perfusion. Impaired CFR is a manifestation of myocardial ischemia which may precede clinical CV events (and visible changes in plaque morphology) in high-risk patients with psoriatic disease. From previous studies, it is known that traditional risk factors underestimate cardiovascular risk in psoriatic disease. The central hypothesis of this study, is that MTS therapy - which has known pleiotropic CV risk reduction effects, including anti-inflammatory properties -- will quantitatively improve myocardial blood flow and CFR as measured by positron emission tomography (PET) over one year and reduce atherosclerotic burden, in patients with moderate-severe psoriasis or psoriatic arthritis. In so doing, improvement in coronary vasoreactivity, endothelial function, and tissue perfusion may have beneficial effects on myocardial mechanics, left ventricular deformation and function and, ultimately, symptoms and prognosis.

• Study Type: Interventional
• Phase: Phase 4

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years to 76 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age > 40 years of age
• Documented evidence of PsO or PsA by a board-certified dermatologist or rheumatologist, respectively.
• Subjects on systemic therapy/phototherapy for PsO or PsA will be required to be on stable therapy for at least 3 months prior to enrollment

Plus, documented history of at least one of the following:

1. Hypertension
2. Obesity (BMI > 30)
3. Diabetes Mellitus
4. HsCRP > 3 mg/L within 30 days of enrollment

Exclusion Criteria:

• Patients on statin or PCSK9 inhibitor therapy, or use of statin therapy within the past year
• Documented history of other systemic inflammatory diseases, which in the opinion of the investigator would be inappropriate for enrollment.
• Prior history of untreated chronic infection (tuberculosis), severe fungal infection, or known HIV positive, chronic hepatitis B or C infection), prior history of solid malignancy, myeloproliferative or lymphoproliferative disease within 5 years, excluding treated non-melanoma skin cancer
• NYHA class IV heart failure
• Active liver disease including unexplained, persistent elevations of serum transaminases or serum transaminase elevation > 3 x the upper limit of normal.
• Severe renal impairment
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single-Arm Open label; This is a single-arm open label mechanistic clinical trial. Subjects will be treated with rosuvastatin at a dose of 20mg/day and uptitrated as tolerated to a dose of 40mg/day.	Drug: Rosuvastatin; Statin; Other Names: Crestor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Coronary Flow Reserve (CFR)	CFR will be measured by cardiac PET at baseline prior to initiating treatment and following 12 months of statin therapy.	Baseline and 12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the total coronary plaque burden measured by cardiac CT angiography (CCTA)	Total coronary plaque burden will be assess by CCTA at baseline and following 12 months of statin therapy	Baseline and 12 months
Change in change in LV peak global longitudinal strain (GLS) (systolic function), measured by transthoracic echocardiogram (TTE)	GLS will be measured by TTE at baseline and following 12 months of statin therapy	Baseline and 12 months
Change in tissue Doppler mitral annular early diastolic relaxation velocity (E') (diastolic function), measured by transthoracic echocardiogram (TTE)	E' will be measured by TTE at baseline and following 12 months of statin therapy	Baseline and 12 months

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: The Cleveland Clinic

Study record dates

Study Major Dates

• Study Start (Anticipated): April 1, 2021
• Primary Completion (Anticipated): March 31, 2025
• Study Completion (Anticipated): March 31, 2025

Study Registration Dates

• First Submitted: June 2, 2020
• First Submitted That Met QC Criteria: June 2, 2020
• First Posted (Actual): June 4, 2020

Study Record Updates

• Last Update Posted (Actual): July 23, 2021
• Last Update Submitted That Met QC Criteria: July 19, 2021
• Last Verified: July 1, 2021

More Information

Terms related to this study

• Keywords: Coronary microvascular function
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Joint Diseases; Musculoskeletal Diseases; Arthritis; Skin Diseases, Papulosquamous; Spinal Diseases; Bone Diseases; Spondylarthropathies; Spondylarthritis; Spondylitis; Inflammation; Psoriasis; Arthritis, Psoriatic; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antimetabolites; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Rosuvastatin Calcium
• Other Study ID Numbers: BWH TBD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes