Study of TNF-Antagonism in Metabolic Syndrome

Metabolic Syndrome Clinical Trial

Official title:

Effects of TNF-Alpha Antagonism in Patients With the Metabolic Syndrome (I)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00409318
• Other study ID #: 2003-P-001699
• Status: Completed
• Phase: N/A
• First received: December 7, 2006
• Last updated: May 23, 2008
• Start date: April 2004
• Est. completion date: May 2005

Study information

• Verified date: May 2008
• Source: Massachusetts General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This study investigates whether blockade of TNF will result in reduced inflammatory indices in patients with the metabolic syndrome

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 information / eligibility

• Status: Completed
• Enrollment: 56
• Est. completion date: May 2005
• Est. primary completion date: May 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

Inclusion Criteria based on a modified WHO definition of metabolic syndrome

1. 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:

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

3. 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

4. Hypertension defined as blood pressure >= 140/90 or on medication

Exclusion Criteria:

1. Positive PPD (³ 5mm induration) on screening

2. Current Infection

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

4. Reception of live vaccine within 1 week of recruitment

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

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

7. History of organ transplantation

8. History of CNS demyelinating disorder or any first degree relative with multiple sclerosis

9. History of CHF classes I-IV

10. Current use of insulin, any oral anti-hyperglycemic agents, pentoxyfylline, beta-agonists

11. Current use of fibrate or niacin

12. Initiation of statin therapy within prior 6 weeks or expecting a change in statin dose over the upcoming 3 months

13. Hemoglobin < 11 g/dl

14. Positive pregnancy test

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

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X
• Syndrome

Intervention

Drug:
• Etanercept
50 mg SC q week
• Placebo
SC q week

Locations

Country	Name	City	State
United States	MGH	Boston	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Massachusetts General Hospital	Amgen

Country where clinical trial is conducted

United States, 

References & Publications (1)

Bernstein LE, Berry J, Kim S, Canavan B, Grinspoon SK. Effects of etanercept in patients with the metabolic syndrome. Arch Intern Med. 2006 Apr 24;166(8):902-8. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CRP		4 weeks	No
Secondary	Insulin resistance		4 weeks	No
Secondary	Muscle adiposity		4 weeks	No
Secondary	High molecular weight adiponectin		4 weeks	No
Secondary	resistin		4 weeks	No
Secondary	leptin		4 weeks	No
Secondary	TNF-R1		4 weeks	No
Secondary	TNF-R2		4 weeks	No
Secondary	weight		4 weeks	No
Secondary	WBC		4 weeks	Yes
Secondary	Lipids		4 weeks	No
Secondary	IL-6		4 weeks	No
Secondary	Fibrinogen		4 weeks	No
Secondary	adiponectin		4 weeks	No