Effects of TNF-alpha Antagonism (Etanercept) in Patients With the Metabolic Syndrome and Psoriasis

Study Overview
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Brief Summary
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People with psoriasis have significantly higher rates of obesity, diabetes, heart failure and high blood pressure than the general public. The purpose of this study is to determine how substances produced in the fat (inflammatory markers) relate to the risk of heart disease in people with the metabolic syndrome and psoriasis. People with metabolic syndrome have insulin resistance, increased waist size, high blood pressure, or high cholesterol.

Detailed Description
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People with psoriasis have significantly higher rates of obesity, diabetes, heart failure and high blood pressure than the general public. The purpose of this study is to determine how substances produced in the fat (inflammatory markers) relate to the risk of heart disease in people with the metabolic syndrome and psoriasis. People with metabolic syndrome have insulin resistance, increased waist size, high blood pressure, or high cholesterol. Insulin resistance means that the body does not respond well to the insulin in your blood. Therefore, both blood levels of insulin and glucose (sugar) are high. This causes inflammation (irritation) in the body. Inflammation can cause an unhealthy response in your body and blood vessels, and can lead to blockages in the heart and other vessels. TNF-alpha is a substance made by fat and inflammatory cells that helps cause inflammatory reactions. TNF-alpha is thought to be important in causing psoriasis. The drug Etanercept blocks TNF-alpha's actions, and has been approved by the Food and Drug Administration (FDA) for the treatment of psoriasis. We think that Etanercept may also reduce the inflammation associated with metabolic syndrome and decrease the risk of heart disease. All subjects in this study will receive etanercept.

Official Title
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Effects of TNF-alpha Antagonism (Etanercept) in Patients With the Metabolic Syndrome and Psoriasis

Conditions
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Psoriasis, Metabolic Syndrome, Hyperlipidemia, Obesity, Hypertension

Intervention / Treatment
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* Drug: Etanercept


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age > 18 Subject willing and able to give informed consent. Adult patients with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. PASI > 10 and BSA affected with psoriasis > 10. Abdominal obesity defined by waist hip ratio > 0.90 for men and > 0.85 for women and BMI ³ 30 kg/m2 Exclusion Criteria: On insulin or other diabetes (anti-hyperglycemic) medication Congestive Heart Failure Heart Attack, Stroke or Transient Ischemic Attack in last 3 months Unstable angina Pulmonary disease requiring oxygen SLE, optic neuritis, transverse myelitis, epilepsy Positive PPD Scheduled for upcoming surgery Known immunosuppression (for example, HIV) Known autoimmune disease Hepatitis B or Hepatitis C Pregnant or nursing Renal insufficiency (Creatinine >1.5) Latex allergy Use of live vaccination in past 90 days Organ transplantation History of severe infection History of malignancy (except cured non-melanoma skin cancer)

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Etanercept<br>Etanercept | Drug: Etanercept<br>* TNF-alpha antagonist 50 mg twice a week x 3 mos and the 50 mg once a week for 3 months.<br>* Other names: Enbrel;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in CRP Levels From Baseline to 6 Months of Treatment in Subjects With Psoriasis and Metabolic Syndrome | Analyzing the difference in C reactive protein levels from baseline to month 6 in subjects with Psoriasis and Metabolic Syndrome | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Plasma Glucose in Subjects With Psoriasis and Metabolic Syndrome | Analyzing the difference in plasma glucose in subjects with Psoriasis and Metabolic Syndrome between baseline and month 6. | 6 months | 
| Change of Endothelial Function by Measurement of Flow-mediated Vasodilation Using the Reactive Hyperemia Index (RHI) in 6 Months | Reactive hyperemia index (RHI) is a measure of endothelial dysfunction using noninvasive peripheral arterial tonometry (PAT). It is a ratio of the post-to-pre occlusion PAT amplitude of the tested arm, divided by the post -to-pre occlusion ratio of the control arm. RHI less than 1.67 is considered sign of endothelial dysfunction. The possible range of scores is 1 to 3 and a lower score has a worse outcome. | 6 months | 
| Change in the Safety and Tolerability of Etanercept in Patients With Psoriasis and Metabolic Syndrome Over a 6-month Period. | Analyzing the safety and tolerability of Etanercept which is being measured through the number of adverse events related to Entanercept over a 6-month period. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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psoriasis, metabolic syndrome, Syndrome X, diabetes, insulin resistance, obesity, hypertension, hyperlipidemia, hypercholesterolemia