SystemIc iNflammation and Microvascular diSease PreventIon in psoRiatic diseasE
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 主要终点
- Change in Coronary Flow Reserve (CFR)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 40 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Rosuvastatin (Drug)
结局指标
主要结局
Change in Coronary Flow Reserve (CFR)
时间窗: Baseline and 12 months
CFR will be measured by cardiac PET at baseline prior to initiating treatment and following 12 months of statin therapy.
次要结局
- Change in the total coronary plaque burden measured by cardiac CT angiography (CCTA)(Baseline and 12 months)
- Change in change in LV peak global longitudinal strain (GLS) (systolic function), measured by transthoracic echocardiogram (TTE)(Baseline and 12 months)
- Change in tissue Doppler mitral annular early diastolic relaxation velocity (E') (diastolic function), measured by transthoracic echocardiogram (TTE)(Baseline and 12 months)
研究者
Marcelo F. Di Carli, MD, FACC
Chief Division of Nuclear Medicine and Molecular Imaging, Executive Director CV Imaging Program, Principal Investigator, Seltzer Family Professor of Radiology and Medicine
Brigham and Women's Hospital