Study of TNF-Antagonism in Metabolic Syndrome
- Registration Number
- NCT00409318
- Lead Sponsor
- Massachusetts General Hospital
- Brief Summary
This study investigates whether blockade of TNF will result in reduced inflammatory indices in patients with the metabolic syndrome
- Detailed Description
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). 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, but have not been examined in the metabolic syndrome population. Moreover, 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. We propose a study in which we administer etanercept, a TNF-alpha receptor fusion protein, to subjects with metabolic syndrome to examine its effect on inflammatory markers,CRP, adiponectin and insulin resistance. This would be the first study to investigate the anti-inflammatory properties and insulin sensitizing potential of TNF-alpha blockade on the growing population with metabolic syndrome.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 56
Inclusion Criteria based on a modified WHO definition of metabolic syndrome
-
Hyperinsulinemia in the upper quartile of the non-diabetic population defined as >= 10 mU/mL (Framingham Data, oral communication,James Meigs, MD) or fasting glucose 110-126 mg/dL
Plus two of the following:
-
Abdominal obesity defined by waist hip ratio > 0.90 for men and > 0.85 for women or BMI > 30 kg/m2
-
Dyslipidemia including serum triglycerides ³ 150 mg/dl or serum HDL < 0.9 mmol/L for men (35 mg/dL) and < 1.0 mmol/L (39mg/dL) for women
-
Hypertension defined as blood pressure >= 140/90 or on medication
- Positive PPD (³ 5mm induration) on screening
- Current Infection
- Therapy with glucocorticoid or immunosuppressant at time of recruitment or within past 3 months
- Reception of live vaccine within 1 week of recruitment
- History of blood dyscrasia including any kind of anemia, thrombocytopenia, pancytopenia. Women with a reversible cause of anemia that has resolved will be eligible.
- History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers who will be eligible)
- History of organ transplantation
- History of CNS demyelinating disorder or any first degree relative with multiple sclerosis
- History of CHF classes I-IV
- Current use of insulin, any oral anti-hyperglycemic agents, pentoxyfylline, beta-agonists
- Current use of fibrate or niacin
- Initiation of statin therapy within prior 6 weeks or expecting a change in statin dose over the upcoming 3 months
- Hemoglobin < 11 g/dl
- Positive pregnancy test
- Women of child-bearing potential not currently using non-hormonal birth control methods including barrier methods (IUD, condoms, diaphragms) or abstinence
- Patients with known autoimmune or inflammatory conditions (excluding patients with stable, treated hypothyroidism)
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 1 Etanercept Etanercept 2 Placebo Placebo
- Primary Outcome Measures
Name Time Method CRP 4 weeks
- Secondary Outcome Measures
Name Time Method Insulin resistance 4 weeks Muscle adiposity 4 weeks High molecular weight adiponectin 4 weeks resistin 4 weeks leptin 4 weeks TNF-R1 4 weeks TNF-R2 4 weeks weight 4 weeks WBC 4 weeks Lipids 4 weeks IL-6 4 weeks Fibrinogen 4 weeks adiponectin 4 weeks
Trial Locations
- Locations (1)
MGH
🇺🇸Boston, Massachusetts, United States