Study of TNF-Antagonism in Metabolic Syndrome

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00409318
Recruitment Status : Completed
First Posted : December 8, 2006
Last Update Posted : May 28, 2008
Information provided by:
Massachusetts General Hospital

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

Condition or disease Intervention/treatment Phase
Metabolic Syndrome Drug: Etanercept Drug: Placebo Not Applicable

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 56 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effects of TNF-Alpha Antagonism in Patients With the Metabolic Syndrome (I)
Study Start Date : April 2004
Actual Primary Completion Date : May 2005
Actual Study Completion Date : May 2005

Resource links provided by the National Library of Medicine

Drug Information available for: Etanercept
U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: 1
Drug: Etanercept
50 mg SC q week
Other Name: Enbrel
Placebo Comparator: 2
Drug: Placebo
SC q week

Primary Outcome Measures :
  1. CRP [ Time Frame: 4 weeks ]

Secondary Outcome Measures :
  1. Insulin resistance [ Time Frame: 4 weeks ]
  2. Muscle adiposity [ Time Frame: 4 weeks ]
  3. High molecular weight adiponectin [ Time Frame: 4 weeks ]
  4. resistin [ Time Frame: 4 weeks ]
  5. leptin [ Time Frame: 4 weeks ]
  6. TNF-R1 [ Time Frame: 4 weeks ]
  7. TNF-R2 [ Time Frame: 4 weeks ]
  8. weight [ Time Frame: 4 weeks ]
  9. WBC [ Time Frame: 4 weeks ]
  10. Lipids [ Time Frame: 4 weeks ]
  11. IL-6 [ Time Frame: 4 weeks ]
  12. Fibrinogen [ Time Frame: 4 weeks ]
  13. adiponectin [ Time Frame: 4 weeks ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00409318

United States, Massachusetts
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Principal Investigator: Steven K Grinspoon MGH

Publications of Results:
Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Steven Grinspoon, M.D., MGH Identifier: NCT00409318     History of Changes
Other Study ID Numbers: 2003-P-001699
First Posted: December 8, 2006    Key Record Dates
Last Update Posted: May 28, 2008
Last Verified: May 2008

Keywords provided by Massachusetts General Hospital:
Visceral adiposity
Insulin resistance
metabolic syndrome

Additional relevant MeSH terms:
Metabolic Syndrome X
Pathologic Processes
Insulin Resistance
Glucose Metabolism Disorders
Metabolic Diseases
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Antirheumatic Agents
Gastrointestinal Agents
Immunosuppressive Agents
Immunologic Factors