Effects of Tumor Necrosis Factor (TNF)-Alpha Antagonism in Patients With Metabolic Syndrome

• Status: Completed
• Trial end date: 2005-05-01
• Target enrollment: 0
• Participant gender: All

Summary

Metabolic syndrome is associated with increased inflammatory cytokines and reduced adiponectin, that may be mediated in part by TNF production from abdominal fat. We reasoned that an anti-TNF agent would reduce C-reactive protein (CRP) and increase adiponectin, improving the inflammatory milieu associated with metabolic syndrome.

• Phase: Phase 2/Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Collaborator: Massachusetts General Hospital
• Treatments: Etanercept

Criteria

Inclusion Criteria:

• 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 *body mass index (BMI) > 30 kg/m2

• Dyslipidemia including serum triglycerides ≥150 mg/dl or serum HDL < 0.9 mmol/L for men (35 mg/dL) and < 1.0 mmol/L (39 mg/dL) for women

• Hypertension defined as blood pressure ≥ 140/90 or on medication

Exclusion Criteria:

• Positive PPD (≥ 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 central nervous system (CNS) demyelinating disorder or any first degree relative with multiple sclerosis

• History of congestive heart failure (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 (intrauterine device (IUD), condoms, diaphragms) or abstinence

• Patients with known autoimmune or inflammatory conditions