Study of TNF-Antagonism in the Metabolic Syndrome (II)

• Status: Completed
• Trial end date: 2009-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This study will investigate whether etanercept will result in improved inflammatory indices, glucose tolerance and endothelial function in patients with the metabolic syndrome.

• Phase: N/A
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Massachusetts General Hospital
• Collaborator: Amgen
• Treatments: Etanercept

Criteria

Inclusion Criteria:

1. Hyperinsulinemia in the upper quartile of the non-diabetic population defined as >= 10 mU/mL (based on Framingham Data, oral communication, James Meigs, MD) or fasting glucose 110-126 mg/dL

2. Plus two of the following:

• Abdominal obesity defined by waist hip ratio > 0.90 for men and > 0.85 for women and BMI > 30 kg/m2

• Dyslipidemia including serum triglycerides >= 150 mg/dl or serum high density lipoprotein (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

Exclusion Criteria:

1. Age < 18 or > 60 years

2. Body mass index (BMI) < 30 kg/m2

3. Positive tuberculosis (purified protein derivative [PPD]) skin test (5mm induration or more) on screening

4. Mycobacterial disease treated less than 6 months.

5. Current or recurrent infection or any underlying condition that may predispose to infection or anyone who has been admitted to the hospital due to bacteremia, pneumonia or any other serious infection.

6. Therapy with glucocorticoid or immunosuppressant at time of recruitment or within past 3 months.

7. Prior or concurrent cyclophosphamide therapy

8. Use of a live vaccine 90 days prior to, or during this study.

9. History of blood dyscrasia including any kind of anemia, thrombocytopenia, pancytopenia. Women with a reversible cause of anemia that has resolved will be eligible.

10. Hemoglobin < 11 g/dl

11. History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers who will be eligible)

12. History of organ transplantation

13. HIV-positive status determined by HIV test at screening or known history of any other immuno-suppressing disease.

14. Hepatitis B or hepatitis C infection detected at screening, lupus (SLE), history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy

15. Patients with known autoimmune or inflammatory conditions (excluding patients with stable, treated hypothyroidism)

16. Severe comorbidities (diabetes mellitus requiring insulin, congestive heart failure (CHF) (EF<50% at baseline will be exclusionary) of any severity, myocardial infarction (MI), cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 3 months of screening visit, unstable angina pectoris, oxygen-dependent severe pulmonary disease

17. Uncontrolled systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg

18. Fasting blood glucose > 126 mg/dL

19. Creatinine > 1.5

20. Current use of insulin, any oral anti-hyperglycemic agents (including insulin sensitizing agents). Initiation of insulin, oral hypoglycemics, or insulin sensitizing agents during the study will result in discontinuation from the study.

21. Initiation of statins, niacin, antihypertensive or fibrate therapy within 6 weeks of the study. Chronic use of fibrates, niacin, or antihypertensives for > 6 weeks prior to study initiation at a stable dose is not exclusionary, but chronic use of statins for > 6 months is exclusionary. Initiation of statins, fibrates, niacin or antihypertensive treatments during the study is not exclusionary but will be considered in the analysis (see Protection against risks).

22. Positive pregnancy test or lactating females

23. Women of child-bearing potential not currently using non-hormonal birth control methods including barrier methods (intrauterine device [IUD], condoms, diaphragms) or abstinence

24. Subject is currently enrolled in another investigational device or drug trial(s), or subject has received other investigational agent(s) within 28 days of baseline visit.

25. Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept

26. Concurrent sulfasalazine therapy

27. History of recent alcohol or substance abuse (< 1 year)

28. Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient.

29. History of non-compliance with other therapies