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Study of TNF-Antagonism in Metabolic Syndrome

Primary Purpose

Metabolic Syndrome

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Etanercept

Placebo

About this trial

This is an interventional treatment trial for Metabolic Syndrome focused on measuring Inflammation, Visceral adiposity, TNF, CRP, Adiponectin, Insulin resistance, metabolic syndrome

Eligibility Criteria

18 Years - 55 Years (Adult)All SexesDoes not accept healthy volunteers

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)

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

Etanercept

Placebo

Outcomes

Primary Outcome Measures

CRP

Secondary Outcome Measures

Insulin resistance

Muscle adiposity

High molecular weight adiponectin

resistin

leptin

TNF-R1

TNF-R2

weight

WBC

Lipids

IL-6

Fibrinogen

adiponectin

Full Information

NCT ID

NCT00409318

First Posted

December 7, 2006

Last Updated

May 23, 2008

Sponsor

Massachusetts General Hospital

Collaborators

Amgen

1. Study Identification

Unique Protocol Identification Number

NCT00409318

Brief Title

Study of TNF-Antagonism in Metabolic Syndrome

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

May 2008

Overall Recruitment Status

Completed

Study Start Date

April 2004 (undefined)

Primary Completion Date

May 2005 (Actual)

Study Completion Date

May 2005 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor

Massachusetts General Hospital

Collaborators

Amgen

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

Brief Summary

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

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Metabolic Syndrome

Keywords

Inflammation, Visceral adiposity, TNF, CRP, Adiponectin, Insulin resistance, metabolic syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

56 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

Etanercept

Arm Title

Arm Type

Placebo Comparator

Arm Description

Placebo

Intervention Type

Drug

Intervention Name(s)

Etanercept

Other Intervention Name(s)

Enbrel

Intervention Description

50 mg SC q week

Intervention Type

Drug

Intervention Name(s)

Placebo

Intervention Description

SC q week

Primary Outcome Measure Information:

Title

CRP

Time Frame

4 weeks

Secondary Outcome Measure Information:

Title

Insulin resistance

Time Frame

4 weeks

Title

Muscle adiposity

Time Frame

4 weeks

Title

High molecular weight adiponectin

Time Frame

4 weeks

Title

resistin

Time Frame

4 weeks

Title

leptin

Time Frame

4 weeks

Title

TNF-R1

Time Frame

4 weeks

Title

TNF-R2

Time Frame

4 weeks

Title

weight

Time Frame

4 weeks

Title

WBC

Time Frame

4 weeks

Title

Lipids

Time Frame

4 weeks

Title

IL-6

Time Frame

4 weeks

Title

Fibrinogen

Time Frame

4 weeks

Title

adiponectin

Time Frame

4 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

55 Years

Accepts Healthy Volunteers

Eligibility 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)

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Steven K Grinspoon

Organizational Affiliation

MGH

Official's Role

Principal Investigator

Facility Information:

Facility Name

MGH

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02114

Country

United States

12. IPD Sharing Statement

Citations:

PubMed Identifier

16636217

Citation

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. doi: 10.1001/archinte.166.8.902.

Results Reference

result

PubMed Identifier

19878508

Citation

Zanni MV, Stanley TL, Makimura H, Chen CY, Grinspoon SK. Effects of TNF-alpha antagonism on E-selectin in obese subjects with metabolic dysregulation. Clin Endocrinol (Oxf). 2010 Jul;73(1):48-54. doi: 10.1111/j.1365-2265.2009.03741.x.

Results Reference

derived

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Study of TNF-Antagonism in Metabolic Syndrome

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