Study of TNF-Antagonism in Metabolic Syndrome - Full Text View

Sponsors and Collaborators:	Massachusetts General Hospital Amgen
Information provided by:	Massachusetts General Hospital
ClinicalTrials.gov Identifier:	NCT00409318

Purpose

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

Condition	Intervention
Metabolic Syndrome	Drug: Etanercept Drug: Placebo

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title:	Effects of TNF-Alpha Antagonism in Patients With the Metabolic Syndrome (I)

Resource links provided by NLM:

Drug Information available for: Etanercept

U.S. FDA Resources

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:

CRP [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Insulin resistance [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Muscle adiposity [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
High molecular weight adiponectin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
resistin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
leptin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
TNF-R1 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
TNF-R2 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
weight [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
WBC [ Time Frame: 4 weeks ] [ Designated as safety issue: Yes ]
Lipids [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
IL-6 [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
Fibrinogen [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]
adiponectin [ Time Frame: 4 weeks ] [ Designated as safety issue: No ]

Enrollment:	56
Study Start Date:	April 2004
Study Completion Date:	May 2005
Primary Completion Date:	May 2005 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Etanercept	Drug: Etanercept 50 mg SC q week
2: Placebo Comparator Placebo	Drug: Placebo SC q week

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.

Eligibility

Ages Eligible for Study:	18 Years to 55 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00409318

Locations

United States, Massachusetts
MGH
Boston, Massachusetts, United States, 02114

Sponsors and Collaborators

Massachusetts General Hospital

Amgen

Investigators

Principal Investigator:

Steven K Grinspoon

MGH

More Information

Publications:

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.

Responsible Party:	MGH ( Steven Grinspoon, M.D. )
Study ID Numbers:	2003-P-001699
Study First Received:	December 7, 2006
Last Updated:	May 23, 2008
ClinicalTrials.gov Identifier:	NCT00409318 History of Changes
Health Authority:	United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:

Inflammation
Visceral adiposity
TNF
CRP

Adiponectin
Insulin resistance
metabolic syndrome

Study placed in the following topic categories:

Anti-Inflammatory Agents
Obesity
Immunologic Factors
TNFR-Fc fusion protein
Immunosuppressive Agents
Insulin
Inflammation

Analgesics, Non-Narcotic
Anti-Inflammatory Agents, Non-Steroidal
Insulin Resistance
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents

Additional relevant MeSH terms:

Anti-Inflammatory Agents
Disease
Immunologic Factors
Physiological Effects of Drugs
Gastrointestinal Agents
TNFR-Fc fusion protein
Immunosuppressive Agents
Pharmacologic Actions
Pathologic Processes

Analgesics, Non-Narcotic
Sensory System Agents
Syndrome
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Analgesics
Peripheral Nervous System Agents
Antirheumatic Agents
Central Nervous System Agents

ClinicalTrials.gov processed this record on September 01, 2009