Monitoring and Modifying Atherosclerosis in Psoriasis Patients Study

Terminated

• Conditions: Psoriasis

• Registration Number: NCT01522742
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The main aims of this study are to determine whether: a) psoriasis patients with or without arthritis have more cardiovascular inflammation than healthy subjects and b)3 months of etanercept (enbrel) therapy (prescribed to psoriasis patients with or without arthritis by their treating clinicians) will decrease cardiovascular inflammation.

Detailed Description

Psoriasis is a common disease characterized by skin lesions and systemic inflammation with or without arthritis. Patients with psoriasis have a higher risk of cardiovascular disease than healthy subjects, and this may be related in part to the inflammatory nature of their disease. This study is intended to help provide explanations for the increased cardiovascular disease risk in psoriasis and to assess whether this risk can be reduced by biologic anti-inflammatory therapies prescribed to resolve skin lesions and arthritis.

Study Timeline

• Study First Submitted: 2011-12-29
• Study First Submitted QC: 2012-01-30
• Study Start: 2012-02
• Study First Posted: 2012-02-01
• Primary Completion: 2016-01
• Study Completion: 2016-01
• Status Verified: 2017-03
• Last Update Submitted: 2017-03-15
• Last Update Posted: 2017-03-17

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 29

Inclusion Criteria

-men and women age 18-80 with moderate-to-severe psoriasis (with or without arthritis) newly initiating biologic therapy with etanercept (enbrel) 50 mg once or twice weekly

Exclusion Criteria

• pregnancy or breastfeeding

• women of child-bearing potential refusing to practice abstinence or to use a reliable barrier form of birth control including condoms, IUD, or diaphragm

• history of acute coronary syndrome or coronary artery stenting or surgery, or significant autoimmune/inflammatory disease other than psoriasis or a related psoriatic condition

• previous therapy for psoriasis with a biologic agent within the past 4 months

• new initiation of a statin or antihyperglycemic agent within the past 3 months

• screening hemoglobin < 11

• conditions which would make MDCT coronary angiography/ cardiac FDG-PET protocol unsafe or unfeasible including: significant renal dysfunction with an eGFR by Cockcroft-Gault equation of <60 ml/min, contrast dye allergy, contraindication to beta-blockers (e.g. severe asthma, hypotension, or heart block), or contraindication to nitroglycerin (uninterruptable administration of phosphodiesterase inhibitors), body weight greater than 320 lbs (PET scanner table limitation)

• report by subject of any significant radiation exposure over the course of the year prior to enrollment; significant exposure is defined as:

  • more than 2 myocardial perfusion studies within the past 12 months
  • more than 2 CT angiograms within the past 12 months

• concurrent enrollment in a clinical trial judged by the investigator to introduce concerns about safety or confounding

FOR HEALTHY CONTROL SUBJECTS

Inclusion Criteria:

-men and women age 18-80 without psoriasis

Exclusion Criteria:

• pregnancy or breastfeeding

• women of child-bearing potential refusing to practice abstinence or to use a reliable barrier form of birth control including condoms, IUD, or diaphragm

• history of acute coronary syndrome or coronary artery stenting or surgery, or significant autoimmune/inflammatory disease

• screening hemoglobin < 11

• conditions which would make MDCT coronary angiography/ cardiac FDG-PET protocol unsafe or unfeasible including: significant renal dysfunction with an estimated creatinine clearance by Cockcroft-Gault equation of <60 ml/min, contrast dye allergy, contraindication to beta-blockers (e.g. severe asthma, hypotension, or heart block), or contraindication to nitroglycerin (e.g. continuous administration of phosphodiesterase inhibitors), body weight greater than 320 lbs PET scanner table limitation)

• report by subject of any significant radiation exposure over the course of the year prior to enrollment; significant exposure is defined as:

  • more than 2 myocardial perfusion studies within the past 12 months
  • more than 2 CT angiograms within the past 12 months

• concurrent enrollment in a clinical trial judged by the investigator to introduce concerns about safety or confounding

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Aortic/coronary target to background ratio (TBR) on cardiac FDG-PET.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).	Degree of aortic/coronary atherosclerotic plaque inflammation assessed via cardiac FDG-PET as target to background ratio (TBR) of the standardized uptake value (SUV).

Secondary Outcome Measures

Name	Time	Method
Aortic/coronary atherosclerotic plaque burden on MDCT coronary angiography.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).	Burden of aortic/coronary atherosclerotic plaque as measured by MDCT coronary angiography.
Inflammatory biomarker levels.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).	Levels of inflammatory biomarkers including but not limited to high-sensitivity C-reactive protein, interleukin-6, and TNF-alpha.
Aortic/coronary atherosclerotic plaque morphology on MDCT coronary angiography.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).	Morphology of the aortic/coronary atherosclerotic plaque (e.g. calcification score, vulnerability characteristics) as measured by MDCT coronary angiography.
Lipid and lipoprotein levels.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).	Levels of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, apolipoprotein C-II, apolipoprotein C-III, and apolipoprotein E.
Endothelial function as measured by flow-mediated vasodilation.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).
Oral glucose tolerance.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).	Blood sugar and insulin levels during a standard 2-hour oral glucose tolerance test.
Body fat distribution.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).	Measurements of height, weight, waist-to-hip ratio, leg circumference, arm circumference, and neck circumference. Determinations by whole body DEXA scanning of the total body and regional percent fat and lean body mass. Determination by single-slice abdominal computed tomography of total fat area, visceral adipose tissue, and subcutaneous adipose tissue.

Trial Locations

Locations (1)

Massachusetts General Hospital; 🇺🇸 Boston, Massachusetts, United States