- ICH GCP
- Registro degli studi clinici negli Stati Uniti
- Sperimentazione clinica NCT00413400
Study of TNF-Antagonism in the Metabolic Syndrome (II)
3 novembre 2010 aggiornato da: Massachusetts General Hospital
Effects of Etanercept in Patients With the Metabolic Syndrome (II)
This study will investigate whether etanercept will result in improved inflammatory indices, glucose tolerance and endothelial function in patients with the metabolic syndrome.
Panoramica dello studio
Stato
Completato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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).
Tumor Necrosis Factor (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.
Tipo di studio
Interventistico
Iscrizione (Effettivo)
40
Fase
- Non applicabile
Contatti e Sedi
Questa sezione fornisce i recapiti di coloro che conducono lo studio e informazioni su dove viene condotto lo studio.
Luoghi di studio
-
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Massachusetts
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Boston, Massachusetts, Stati Uniti, 02114
- MGH
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-
Criteri di partecipazione
I ricercatori cercano persone che corrispondano a una certa descrizione, chiamata criteri di ammissibilità. Alcuni esempi di questi criteri sono le condizioni generali di salute di una persona o trattamenti precedenti.
Criteri di ammissibilità
Età idonea allo studio
Da 18 anni a 60 anni (Adulto)
Accetta volontari sani
No
Sessi ammissibili allo studio
Tutto
Descrizione
Inclusion Criteria:
- 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
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 high density lipoprotein (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:
- Age < 18 or > 60 years
- Body mass index (BMI) < 30 kg/m2
- Positive tuberculosis (purified protein derivative [PPD]) skin test (5mm induration or more) on screening
- Mycobacterial disease treated less than 6 months.
- 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.
- Therapy with glucocorticoid or immunosuppressant at time of recruitment or within past 3 months.
- Prior or concurrent cyclophosphamide therapy
- Use of a live vaccine 90 days prior to, or during this study.
- History of blood dyscrasia including any kind of anemia, thrombocytopenia, pancytopenia. Women with a reversible cause of anemia that has resolved will be eligible.
- Hemoglobin < 11 g/dl
- History of malignancy (except patients with surgically cured basal cell or squamous cell skin cancers who will be eligible)
- History of organ transplantation
- HIV-positive status determined by HIV test at screening or known history of any other immuno-suppressing disease.
- Hepatitis B or hepatitis C infection detected at screening, lupus (SLE), history of multiple sclerosis, transverse myelitis, optic neuritis or epilepsy
- Patients with known autoimmune or inflammatory conditions (excluding patients with stable, treated hypothyroidism)
- Severe comorbidities (diabetes mellitus requiring insulin, congestive heart failure (CHF) (EF<50% at baseline will be exclusionary) of any severity, myocardial infarction (MI), cerebral vascular accident (CVA) or transient ischemic attack (TIA) within 3 months of screening visit, unstable angina pectoris, oxygen-dependent severe pulmonary disease
- Uncontrolled systolic blood pressure > 150 mmHg or diastolic blood pressure > 100 mmHg
- Fasting blood glucose > 126 mg/dL
- Creatinine > 1.5
- 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.
- 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).
- Positive pregnancy test or lactating females
- Women of child-bearing potential not currently using non-hormonal birth control methods including barrier methods (intrauterine device [IUD], condoms, diaphragms) or abstinence
- 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.
- Subjects who have known hypersensitivity to Enbrel or any of its components or who is known to have antibodies to etanercept
- Concurrent sulfasalazine therapy
- History of recent alcohol or substance abuse (< 1 year)
- Any condition judged by the patient's physician to cause this clinical trial to be detrimental to the patient.
- History of non-compliance with other therapies
Piano di studio
Questa sezione fornisce i dettagli del piano di studio, compreso il modo in cui lo studio è progettato e ciò che lo studio sta misurando.
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Doppio
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
---|---|
Comparatore placebo: Placebo
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50 mg one syringe sc 2x per week for three months followed by 50 mg one syringe sc 1X per week for three months
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Comparatore attivo: Etanercept
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50 mg one syringe sc 2X per week for three months followed by 50 mg one syringe sc 1X per week for three months
Altri nomi:
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Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
C-reactive Protein (CRP)
Lasso di tempo: 6 months
|
As a measure of C-reactive protein (CRP), which is an inflammatory marker, Log10 of the CRP at 6 months is reported
|
6 months
|
Interleukin-6 (IL-6)
Lasso di tempo: 6 months
|
6 month value of IL-6 (pg/mL)
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6 months
|
Adiponectin
Lasso di tempo: 6 months
|
The ratio of circulating high molecular weight (HMW) adiponectin to total adiponectin ratio (HMW:total Adiponectin) at 6 months is reported.
|
6 months
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
---|---|---|
Glucose Tolerance
Lasso di tempo: 6 months
|
Fasting glucose (mg/dL) at 6mo
|
6 months
|
Endothelial Function
Lasso di tempo: 6 months
|
Reactive Hyperemia Index (RHI) using peripheral artery tonometry (using Endo-PAT 2000).
Peripheral artery tonometry measures blood flow in the tip of the index finger at baseline and in response to vaso-occlusion (inflated blood pressure cuff).
The reactive hyperemia index is an index of vasodilation after occlusion compared to baseline.
A higher value indicates better vasoreactivity.
As this is a relatively new test, there are no thoroughly validated clinically utilized norms.
|
6 months
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White Blood Cell (WBC) Count
Lasso di tempo: Baseline to 6 months
|
Change in WBC during study (WBC at six months minus WBC at baseline)
|
Baseline to 6 months
|
Cardiac Echo Ejection Fraction (EF)
Lasso di tempo: Baseline to 6 months
|
change in EF (6mo - baseline).
Please note that the value given is the absolute change in EF (which has units of percent), not the percent change in the variable.
|
Baseline to 6 months
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Body Composition
Lasso di tempo: 6 months
|
6 month visceral adipose tissue (cm^2) - cross-sectional area of the visceral adipose tissue at the level of the 4th lumbar vertebrae was measured using single-slice abdominal computed tomography (CT) scan
|
6 months
|
Tumor Necrosis Factor (TNF) Receptor
Lasso di tempo: 6 months
|
Circulating concentrations of Tumor necrosis factor receptor 2 (TNFR2) at 6 months
|
6 months
|
Other Adipocytokines
Lasso di tempo: 6 months
|
circulating resistin at 6 months
|
6 months
|
Lipid Levels
Lasso di tempo: 6 months
|
total cholesterol (mg/dL) at 6 months
|
6 months
|
Adipocyte Messenger Ribonucleic Acid (mRNA) Levels of Adipocytokines Including Tumor Necrosis Factor (TNF) -Alpha
Lasso di tempo: 6 months
|
fold-change in subcutaneous adipose tissue expression of TNF-alpha (mRNA) after 6 months
|
6 months
|
Collaboratori e investigatori
Qui è dove troverai le persone e le organizzazioni coinvolte in questo studio.
Sponsor
Collaboratori
Investigatori
- Investigatore principale: Steven K Grinspoon, MGH
Studiare le date dei record
Queste date tengono traccia dell'avanzamento della registrazione dello studio e dell'invio dei risultati di sintesi a ClinicalTrials.gov. I record degli studi e i risultati riportati vengono esaminati dalla National Library of Medicine (NLM) per assicurarsi che soddisfino specifici standard di controllo della qualità prima di essere pubblicati sul sito Web pubblico.
Studia le date principali
Inizio studio
1 dicembre 2006
Completamento primario (Effettivo)
1 settembre 2009
Completamento dello studio (Effettivo)
1 settembre 2009
Date di iscrizione allo studio
Primo inviato
7 dicembre 2006
Primo inviato che soddisfa i criteri di controllo qualità
18 dicembre 2006
Primo Inserito (Stima)
19 dicembre 2006
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Stima)
2 dicembre 2010
Ultimo aggiornamento inviato che soddisfa i criteri QC
3 novembre 2010
Ultimo verificato
1 novembre 2010
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Processi patologici
- Disturbi del metabolismo del glucosio
- Malattie metaboliche
- Patologia
- Resistenza all'insulina
- Iperinsulinismo
- Sindrome
- Sindrome metabolica
- Effetti fisiologici delle droghe
- Agenti del sistema nervoso periferico
- Analgesici
- Agenti del sistema sensoriale
- Agenti antinfiammatori, non steroidei
- Analgesici, non narcotici
- Agenti antinfiammatori
- Agenti antireumatici
- Agenti immunosoppressivi
- Fattori immunologici
- Agenti gastrointestinali
- Etanercept
Altri numeri di identificazione dello studio
- 2006-P-001060
Queste informazioni sono state recuperate direttamente dal sito web clinicaltrials.gov senza alcuna modifica. In caso di richieste di modifica, rimozione o aggiornamento dei dettagli dello studio, contattare register@clinicaltrials.gov. Non appena verrà implementata una modifica su clinicaltrials.gov, questa verrà aggiornata automaticamente anche sul nostro sito web .