Etanercept and Vascular Function in Psoriasis
Condition: PSORIASIS
MeSH terms: Psoriasis
Study type: Interventional
Phase: Phase 2

Summary: 
      The investigators plan to measure the health of the vascular system of subjects taking
      Etanercept for the treatment of plaque psoriasis.
    

Detailed description: 
      Psoriasis is a chronic disease that mainly affects the skin. The most common form of
      psoriasis, plaque psoriasis, can appear anywhere on the body, but it is most commonly found
      on the elbows, knees, scalp, and lower back. Skin typically becomes red and inflamed and may
      form scaly patches. While psoriasis may look like just a skin disease, it is in fact a result
      of an overacting, malfunctioning immune system. One consequence of this dysfunction is
      over-activity of a substance called tumor necrosis factor (TNF). TNF alters the body's immune
      response by promoting inflammation. High TNF activity is associated with psoriasis and many
      other diseases of the immune system.

      There are multiple treatments for psoriasis ranging from topical medications including
      steroid creams, coal tar extracts, and exposure to UV light. For moderate to severe disease,
      drugs that change how the immune system works are sometimes used. One of these drugs is
      Etanercept, a prescription medicine approved by the FDA for the treatment of moderate to
      severe plaque psoriasis. Etanercept works by reducing the amount of TNF in the body and
      thereby reducing inflammation and keep skin clearer.

      Inflammation appears on the skin of patients with psoriasis, but recent research has shown
      that abnormal inflammation plays a role in the development of a disease of blood vessels
      called atherosclerosis. Atherosclerosis is the build-up of plaques within arteries in the
      body causing gradual narrowing and occasionally rupturing causing angina (chest pain), heart
      attacks, strokes, and peripheral vascular disease. Many of the traditional risk factors for
      atherosclerosis (including high blood pressure, diabetes, and smoking) are themselves
      associated with increased inflammation.

      These risk factors themselves also increase the production of certain molecules called
      reactive oxygen species. Too many reactive oxygen species molecules results in a condition
      called oxidative stress. Oxidative stress leads to abnormal function of the cells that line
      the blood vessels, called endothelial cells, and this process promotes inflammation within
      the blood vessel. Over time, this leads to irreversible damage to the heart and blood
      vessels.

      To counteract this damage, the body produces endothelial progenitor cells (EPCs) in the bone
      marrow. The EPCs help balance out the damage that occurs in the blood vessels from oxidative
      stress and other harmful processes. Several other drugs commonly used in heart disease have
      recently been shown to improve EPCs function.

      This balance of oxidative stress, inflammation, EPCs and the immune system is complex and not
      fully understood. Drugs like Etanercept that modify the inflammatory response of the immune
      system are useful not only as therapies for diseases like psoriasis, but can help expand
      understanding of inflammation and arthrosclerosis.

      The investigators plan to measure the health of the vascular system of subjects taking
      Etanercept for the treatment of plaque psoriasis. To do that, we plan to take blood samples
      to check for cardiovascular risk factors, inflammation levels, oxidative stress levels, and
      EPCs. The investigators will also measure how well the arteries relax by ultrasound ( a
      non-invasive test). Because we want to measure the effect of Etanercept on the blood vessels
      we will have each subject take Etanercept for 3 months and a placebo injection for 3 months
      checking ultrasound and blood tests at the end of each cycle.

      Subjects in the study will all be individuals who would be eligible to receive Etanercept
      under its current FDA use guidelines (for psoriasis). Our interest is in the potential
      effects of this drug on the vascular system. By performing this study we hope to better
      understand the interplay between vascular disease, inflammation and the immune system. If a
      drug that modulates the inflammatory response causes changes in vascular function, it would
      be an important step towards possible new avenues of treatment of cardiovascular disease.
    

Intervention name(s): Etanercept; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Etanercept 50mg twice weekly
Other intervention name(s): Enbrel
Intervention MeSH terms: Etanercept
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Treatment
Keywords: PSORIASIS