Full Text View  
  Tabular View  
  Contacts and Locations  
  No Study Results Posted  
  Related Studies  
Study of TNF-Antagonism in the Metabolic Syndrome (II)
This study is currently recruiting participants.
Verified by Massachusetts General Hospital, December 2007
Sponsors and Collaborators: Massachusetts General Hospital
Amgen
Information provided by: Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00413400
  Purpose

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


Condition Intervention
Metabolic Syndrome
Drug: Etanercept
Drug: Placebo

Drug Information available for: Etanercept Dextrose
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Investigator), Placebo Control, Parallel Assignment, Safety/Efficacy Study
Official Title: Effects of Etanercept in Patients With the Metabolic Syndrome (II)

Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • CRP [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • IL-6 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Adiponectin [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Glucose tolerance [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • endothelial function [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • WBC [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • cardiac echo [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • body composition [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • TNF-receptors [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • other adipocytokines [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • lipid levels [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Adipocyte RNA levels of macrophage specific markers, Il6, IL1 and TNF-alpha [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Estimated Enrollment: 40
Study Start Date: December 2006
Estimated Study Completion Date: December 2008
Arms Assigned Interventions
1: Placebo Comparator Drug: Placebo
50 mg one syringe sc 2x per week for three months followed by 50 mg one syringe sc 1X per week for three months
2: Active Comparator Drug: Etanercept
50 mg one syringe sc 2X per week for three months followed by 50 mg one syringe sc 1X per week for three months

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, and have recently been shown by our group to decrease inflammatory cardiovascular risk markers in metabolic syndrome. 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. In addition, population based studies have shown that those with the highest levels of TNF-alpha have an increased relative risk of cardiovascular morbidity while rheumatoid arthritis patients treated with TNF-alpha blockade appear protected from cardiovascular disease. We will perform a 6-month study in which we will administer etanercept, a TNF-alpha receptor fusion protein, to subjects with metabolic syndrome to investigate its effect on surrogate markers of cardiovascular disease, including inflammatory markers, adiponectin and glucose tolerance and endothelial function. The results of the proposed study will have broad implications regarding the physiological role of TNF-alpha on the inflammatory cascade, cardiovascular indices and endothelial function.

  Eligibility

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 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 > 55 years
  2. BMI < 30 kg/m2
  3. Positive PPD (³ 5mm induration) 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, 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, CHF (EF<50% at baseline will be exclusionary) of any severity, MI, CVA or 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 (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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00413400

Contacts
Contact: Steven K Grinspoon, MD 617 724-9109 sgrinspoon@partners.org

Locations
United States, Massachusetts
MGH Recruiting
Boston, Massachusetts, United States, 02114
Contact: Steven K Grinspoon, MD     617-724-9109        
Principal Investigator: Steven K Grinspoon, MD            
Sponsors and Collaborators
Massachusetts General Hospital
Amgen
Investigators
Principal Investigator: Steven K Grinspoon MGH
Principal Investigator: Steven K Grinspoon MGH
  More Information

Responsible Party: Massachusetts General Hospital ( Steven Grinspoon, MD )
Study ID Numbers: 2006-P-001060
Study First Received: December 7, 2006
Last Updated: December 14, 2007
ClinicalTrials.gov Identifier: NCT00413400  
Health Authority: United States: Food and Drug Administration

Keywords provided by Massachusetts General Hospital:
Inflammation
Visceral adiposity
TNF
Adiponectin
glucose tolerance
endothelial function
metabolic syndrome

Study placed in the following topic categories:
Obesity
TNFR-Fc fusion protein
Inflammation

Additional relevant MeSH terms:
Anti-Inflammatory Agents
Disease
Immunologic Factors
Physiological Effects of Drugs
Gastrointestinal Agents
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 January 14, 2009