Monitoring and Modifying Atherosclerosis in Psoriasis Patients Study (MMAPPS)

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.

Study Overview

• Status: Terminated
• Conditions: Psoriasis

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 Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects with moderate-to-severe psoriasis with or without arthritis will be recruited primarily from dermatology and rheumatology clinics in the eastern Massachusetts area.

Description

FOR PSORIASIS PATIENTS

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 Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Healthy control subjects; Healthy control subjects matched to psoriasis patients on traditional cardiovascular risk factors will be studied at baseline.
Psoriasis patients starting etanercept; Patients with moderate to severe psoriasis with or without arthritis who are about to be started on etanercept (enbrel) by their treating clinicians will be studied at baseline and 3 months after etanercept therapy.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Aortic/coronary atherosclerotic plaque burden on MDCT coronary angiography.	Burden of aortic/coronary atherosclerotic plaque as measured by MDCT coronary angiography.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).
Aortic/coronary atherosclerotic plaque morphology on MDCT coronary angiography.	Morphology of the aortic/coronary atherosclerotic plaque (e.g. calcification score, vulnerability characteristics) as measured by MDCT coronary angiography.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).
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.	Blood sugar and insulin levels during a standard 2-hour oral glucose tolerance test.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).
Lipid and lipoprotein levels.	Levels of total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides, apolipoprotein A1, apolipoprotein B, apolipoprotein C-II, apolipoprotein C-III, and apolipoprotein E.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).
Inflammatory biomarker levels.	Levels of inflammatory biomarkers including but not limited to high-sensitivity C-reactive protein, interleukin-6, and TNF-alpha.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).
Body fat distribution.	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.	Baseline in all subjects and change from baseline to 3 months in psoriasis cohort starting etanercept (enbrel).

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Immunex Corporation
• Investigators: Principal Investigator: Steven K Grinspoon, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): January 1, 2016
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: December 29, 2011
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Actual): March 17, 2017
• Last Update Submitted That Met QC Criteria: March 15, 2017
• Last Verified: March 1, 2017

More Information

Terms related to this study

• Keywords: atherosclerosis; psoriasis; cardiovascular disease risk; etanercept (enbrel)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Skin Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Skin Diseases, Papulosquamous; Psoriasis; Atherosclerosis
• Other Study ID Numbers: 2011P-000557