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

Primary Purpose

Psoriasis, Psoriatic Arthritis, Cardiovascular Risk Factor

Status

Withdrawn

Phase

Phase 4

Locations

Study Type

Interventional

Intervention

Rosuvastatin

About this trial

This is an interventional prevention trial for Psoriasis focused on measuring Coronary microvascular function

Eligibility Criteria

40 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

Hypertension
Obesity (BMI > 30)
Diabetes Mellitus
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

Sites / Locations

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Single-Arm Open label

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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

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

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

Full Information

NCT ID

NCT04417114

First Posted

June 2, 2020

Last Updated

July 19, 2021

Sponsor

Brigham and Women's Hospital

Collaborators

The Cleveland Clinic

1. Study Identification

Unique Protocol Identification Number

NCT04417114

Brief Title

SystemIc iNflammation and Microvascular diSease PreventIon in psoRiatic diseasE

Acronym

INSPIRE

Official Title

SystemIc iNflammation and Microvascular diSease PreventIon in psoRiatic diseasE

Study Type

Interventional

2. Study Status

Record Verification Date

July 2021

Overall Recruitment Status

Withdrawn

Why Stopped

The study was not funded.

Study Start Date

April 1, 2021 (Anticipated)

Primary Completion Date

March 31, 2025 (Anticipated)

Study Completion Date

March 31, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Brigham and Women's Hospital

Collaborators

The Cleveland Clinic

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Yes

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Psoriasis, Psoriatic Arthritis, Cardiovascular Risk Factor

Keywords

Coronary microvascular function

7. Study Design

Primary Purpose

Prevention

Study Phase

Phase 4

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

0 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Single-Arm Open label

Arm Type

Experimental

Arm Description

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.

Intervention Type

Drug

Intervention Name(s)

Rosuvastatin

Other Intervention Name(s)

Crestor

Intervention Description

Statin

Primary Outcome Measure Information:

Title

Change in Coronary Flow Reserve (CFR)

Description

CFR will be measured by cardiac PET at baseline prior to initiating treatment and following 12 months of statin therapy.

Time Frame

Baseline and 12 months

Secondary Outcome Measure Information:

Title

Change in the total coronary plaque burden measured by cardiac CT angiography (CCTA)

Description

Total coronary plaque burden will be assess by CCTA at baseline and following 12 months of statin therapy

Time Frame

Baseline and 12 months

Title

Change in change in LV peak global longitudinal strain (GLS) (systolic function), measured by transthoracic echocardiogram (TTE)

Description

GLS will be measured by TTE at baseline and following 12 months of statin therapy

Time Frame

Baseline and 12 months

Title

Change in tissue Doppler mitral annular early diastolic relaxation velocity (E') (diastolic function), measured by transthoracic echocardiogram (TTE)

Description

E' will be measured by TTE at baseline and following 12 months of statin therapy

Time Frame

Baseline and 12 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

40 Years

Maximum Age & Unit of Time

80 Years

Accepts Healthy Volunteers

Eligibility Criteria

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: Hypertension Obesity (BMI > 30) Diabetes Mellitus 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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Marcelo Di Carli, MD

Organizational Affiliation

Brigham and Women's Hospital

Official's Role

Principal Investigator

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

SystemIc iNflammation and Microvascular diSease PreventIon in psoRiatic diseasE

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