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

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.

Study Overview

• Status: Terminated
• Conditions: Hypertension; Obesity; Psoriasis; Metabolic Syndrome; Hyperlipidemia
• Intervention / Treatment: Drug: Etanercept

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Not Applicable

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 and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Age > 18
2. Subject willing and able to give informed consent.
3. Adult patients with chronic moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy.
4. PASI > 10 and BSA affected with psoriasis > 10.
5. 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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: Amgen
• Investigators: Principal Investigator: Alexandra B Kimball, MD, MPH, Massachusetts General Hospital, Brigham & Women's Hospital

Study record dates

Study Major Dates

• Study Start: May 1, 2007
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: May 18, 2007
• First Submitted That Met QC Criteria: May 18, 2007
• First Posted (Estimate): May 22, 2007

Study Record Updates

• Last Update Posted (Estimate): May 16, 2016
• Last Update Submitted That Met QC Criteria: April 12, 2016
• Last Verified: April 1, 2016

More Information

Terms related to this study

• Keywords: diabetes; obesity; hypertension; insulin resistance; metabolic syndrome; psoriasis; hypercholesterolemia; Syndrome X; hyperlipidemia
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Skin Diseases; Disease; Skin Diseases, Papulosquamous; Insulin Resistance; Hyperinsulinism; Lipid Metabolism Disorders; Dyslipidemias; Hypertension; Syndrome; Psoriasis; Metabolic Syndrome; Hyperlipidemias; Hyperlipoproteinemias; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Gastrointestinal Agents; Etanercept
• Other Study ID Numbers: 2007-P-000494

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No