Hyperlipidemia, Hypertension, Metabolic Syndrome, Obesity, Psoriasis
Conditions
Keywords
psoriasis, metabolic syndrome, Syndrome X, diabetes, insulin resistance, obesity, hypertension, hyperlipidemia, hypercholesterolemia
Brief summary
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
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.
Interventions
DRUGEtanercept
TNF-alpha antagonist 50 mg twice a week x 3 mos and the 50 mg once a week for 3 months.
Sponsors
Amgen
Massachusetts General Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in CRP Levels From Baseline to 6 Months of Treatment in Subjects With Psoriasis and Metabolic Syndrome | 6 months | Analyzing the difference in C reactive protein levels from baseline to month 6 in subjects with Psoriasis and Metabolic Syndrome |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Plasma Glucose in Subjects With Psoriasis and Metabolic Syndrome | 6 months | Analyzing the difference in plasma glucose in subjects with Psoriasis and Metabolic Syndrome between baseline and month 6. |
| Change of Endothelial Function by Measurement of Flow-mediated Vasodilation Using the Reactive Hyperemia Index (RHI) in 6 Months | 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. |
| Change in the Safety and Tolerability of Etanercept in Patients With Psoriasis and Metabolic Syndrome Over a 6-month Period. | 6 months | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Etanercept Etanercept
Etanercept: TNF-alpha antagonist 50 mg twice a week x 3 mos and then 50 mg once a week for 3 months. | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Etanercept |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 18 Participants |
| Age, Continuous | 43.5 years STANDARD_DEVIATION 11.6 |
| BMI | 38.9 kg/m^2 STANDARD_DEVIATION 5.6 |
| Psoriasis Area Severity Index (PASI) | 16.9 units on a scale STANDARD_DEVIATION 1.5 |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 5 Participants |
| Sex: Female, Male Male | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 4 / 13 |
| serious Total, serious adverse events | 0 / 13 |
Outcome results
Primary
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
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Change in CRP Levels From Baseline to 6 Months of Treatment in Subjects With Psoriasis and Metabolic Syndrome | 5.3 ng/mL | Standard Deviation 4.2 |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Change in Plasma Glucose in Subjects With Psoriasis and Metabolic Syndrome | 13 mg/dl | Standard Deviation 56 |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Etanercept | Change in the Safety and Tolerability of Etanercept in Patients With Psoriasis and Metabolic Syndrome Over a 6-month Period. | 6 number of events |
Secondary
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.
Time frame: 6 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Etanercept | Change of Endothelial Function by Measurement of Flow-mediated Vasodilation Using the Reactive Hyperemia Index (RHI) in 6 Months | 1.57 units on a scale | Standard Deviation 0.21 |