Study of TNF-Antagonism in the Metabolic Syndrome (II)
This study will investigate whether etanercept will result in improved inflammatory indices, glucose tolerance and endothelial function in patients with the metabolic syndrome.
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||Effects of Etanercept in Patients With the Metabolic Syndrome (II)|
- C-reactive Protein (CRP) [ Time Frame: 6 months ] [ Designated as safety issue: No ]As a measure of C-reactive protein (CRP), which is an inflammatory marker, Log10 of the CRP at 6 months is reported
- Interleukin-6 (IL-6) [ Time Frame: 6 months ] [ Designated as safety issue: No ]6 month value of IL-6 (pg/mL)
- Adiponectin [ Time Frame: 6 months ] [ Designated as safety issue: No ]The ratio of circulating high molecular weight (HMW) adiponectin to total adiponectin ratio (HMW:total Adiponectin) at 6 months is reported.
- Glucose Tolerance [ Time Frame: 6 months ] [ Designated as safety issue: No ]Fasting glucose (mg/dL) at 6mo
- Endothelial Function [ Time Frame: 6 months ] [ Designated as safety issue: No ]Reactive Hyperemia Index (RHI) using peripheral artery tonometry (using Endo-PAT 2000). Peripheral artery tonometry measures blood flow in the tip of the index finger at baseline and in response to vaso-occlusion (inflated blood pressure cuff). The reactive hyperemia index is an index of vasodilation after occlusion compared to baseline. A higher value indicates better vasoreactivity. As this is a relatively new test, there are no thoroughly validated clinically utilized norms.
- White Blood Cell (WBC) Count [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: Yes ]Change in WBC during study (WBC at six months minus WBC at baseline)
- Cardiac Echo Ejection Fraction (EF) [ Time Frame: Baseline to 6 months ] [ Designated as safety issue: Yes ]change in EF (6mo - baseline). Please note that the value given is the absolute change in EF (which has units of percent), not the percent change in the variable.
- Body Composition [ Time Frame: 6 months ] [ Designated as safety issue: No ]6 month visceral adipose tissue (cm^2) - cross-sectional area of the visceral adipose tissue at the level of the 4th lumbar vertebrae was measured using single-slice abdominal computed tomography (CT) scan
- Tumor Necrosis Factor (TNF) Receptor [ Time Frame: 6 months ] [ Designated as safety issue: No ]Circulating concentrations of Tumor necrosis factor receptor 2 (TNFR2) at 6 months
- Other Adipocytokines [ Time Frame: 6 months ] [ Designated as safety issue: No ]circulating resistin at 6 months
- Lipid Levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]total cholesterol (mg/dL) at 6 months
- Adipocyte Messenger Ribonucleic Acid (mRNA) Levels of Adipocytokines Including Tumor Necrosis Factor (TNF) -Alpha [ Time Frame: 6 months ] [ Designated as safety issue: No ]fold-change in subcutaneous adipose tissue expression of TNF-alpha (mRNA) after 6 months
|Study Start Date:||December 2006|
|Study Completion Date:||September 2009|
|Primary Completion Date:||September 2009 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Placebo||
50 mg one syringe sc 2x per week for three months followed by 50 mg one syringe sc 1X per week for three months
|Active Comparator: Etanercept||
50 mg one syringe sc 2X per week for three months followed by 50 mg one syringe sc 1X per week for three months
Other Name: Enbrel
Metabolic syndrome is an increasingly prevalent disorder associated with elevated risks of type II DM (diabetes mellitus) and cardiovascular morbidity and mortality. A subclinical inflammatory state is thought to contribute to the pathophysiology of metabolic syndrome, insulin resistance, and coronary artery disease (CAD). Tumor Necrosis Factor (TNF) -alpha is an inflammatory cytokine that is increased in a spectrum of inflammatory diseases as well as in insulin resistance. TNF-alpha antagonists are clinically effective in the inflammation of arthritides, and have recently been shown by our group to decrease inflammatory cardiovascular risk markers in metabolic syndrome. Data suggests that adiponectin, a recently discovered adipocytokine that may protect against the development of insulin resistance and atherosclerosis, may be downregulated by TNF-alpha. In addition, population based studies have shown that those with the highest levels of TNF-alpha have an increased relative risk of cardiovascular morbidity while rheumatoid arthritis patients treated with TNF-alpha blockade appear protected from cardiovascular disease. We will perform a 6-month study in which we will administer etanercept, a TNF-alpha receptor fusion protein, to subjects with metabolic syndrome to investigate its effect on surrogate markers of cardiovascular disease, including inflammatory markers, adiponectin and glucose tolerance and endothelial function. The results of the proposed study will have broad implications regarding the physiological role of TNF-alpha on the inflammatory cascade, cardiovascular indices and endothelial function.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413400
|United States, Massachusetts|
|Boston, Massachusetts, United States, 02114|
|Principal Investigator:||Steven K Grinspoon||MGH|