- ICH GCP
- Amerikanska kliniska prövningsregistret
- Klinisk prövning NCT00413400
Study of TNF-Antagonism in the Metabolic Syndrome (II)
3 november 2010 uppdaterad av: 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.
Studieöversikt
Status
Avslutad
Betingelser
Intervention / Behandling
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
40
Fas
- Inte tillämpbar
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
Massachusetts
-
Boston, Massachusetts, Förenta staterna, 02114
- MGH
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
18 år till 60 år (Vuxen)
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Behandling
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Dubbel
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
---|---|
Placebo-jämförare: 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
|
Aktiv komparator: 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
Andra namn:
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
C-reactive Protein (CRP)
Tidsram: 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)
Tidsram: 6 months
|
6 month value of IL-6 (pg/mL)
|
6 months
|
Adiponectin
Tidsram: 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
|
Sekundära resultatmått
Resultatmått |
Åtgärdsbeskrivning |
Tidsram |
---|---|---|
Glucose Tolerance
Tidsram: 6 months
|
Fasting glucose (mg/dL) at 6mo
|
6 months
|
Endothelial Function
Tidsram: 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
|
White Blood Cell (WBC) Count
Tidsram: 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)
Tidsram: 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
|
Body Composition
Tidsram: 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
Tidsram: 6 months
|
Circulating concentrations of Tumor necrosis factor receptor 2 (TNFR2) at 6 months
|
6 months
|
Other Adipocytokines
Tidsram: 6 months
|
circulating resistin at 6 months
|
6 months
|
Lipid Levels
Tidsram: 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
Tidsram: 6 months
|
fold-change in subcutaneous adipose tissue expression of TNF-alpha (mRNA) after 6 months
|
6 months
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Sponsor
Samarbetspartners
Utredare
- Huvudutredare: Steven K Grinspoon, MGH
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 december 2006
Primärt slutförande (Faktisk)
1 september 2009
Avslutad studie (Faktisk)
1 september 2009
Studieregistreringsdatum
Först inskickad
7 december 2006
Först inskickad som uppfyllde QC-kriterierna
18 december 2006
Första postat (Uppskatta)
19 december 2006
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
2 december 2010
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
3 november 2010
Senast verifierad
1 november 2010
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- Patologiska processer
- Störningar i glukosmetabolism
- Metaboliska sjukdomar
- Sjukdom
- Insulinresistens
- Hyperinsulinism
- Syndrom
- Metaboliskt syndrom
- Läkemedels fysiologiska effekter
- Agenter från det perifera nervsystemet
- Analgetika
- Sensoriska systemagenter
- Antiinflammatoriska medel, icke-steroida
- Analgetika, icke-narkotiska
- Antiinflammatoriska medel
- Antireumatiska medel
- Immunsuppressiva medel
- Immunologiska faktorer
- Gastrointestinala medel
- Etanercept
Andra studie-ID-nummer
- 2006-P-001060
Denna information hämtades direkt från webbplatsen clinicaltrials.gov utan några ändringar. Om du har några önskemål om att ändra, ta bort eller uppdatera dina studieuppgifter, vänligen kontakta register@clinicaltrials.gov. Så snart en ändring har implementerats på clinicaltrials.gov, kommer denna att uppdateras automatiskt även på vår webbplats .
Kliniska prövningar på Metaboliskt syndrom
-
Grand Valley State UniversityAnmälan via inbjudanMetabolic Associated-dysfunction Steatotic Lever Disease (MASLD) | Metabolic Associated-dysfunction Steatohepatit (MASH)Förenta staterna
-
Scripps Whittier Diabetes InstituteAvslutadCardio-metabolic Care-Team Intervention (CMC-TI)
-
Shanghai General Hospital, Shanghai Jiao Tong University...Har inte rekryterat ännuPrediabetes | Kontinuerlig glukosövervakning | Metabolic Management Center
-
Brian JonasNational Cancer Institute (NCI); Celgene; Pharmacyclics LLC.AvslutadTidigare behandlat myelodysplastiskt syndrom | Myelodysplastiskt syndrom | Terapierelaterat myelodysplastiskt syndrom | Sekundärt myelodysplastiskt syndrom | Refraktärt högrisk myelodysplastiskt syndromFörenta staterna
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)AvslutadTidigare behandlade myelodysplastiska syndrom | Sekundära myelodysplastiska syndrom | de Novo myelodysplastiska syndromFörenta staterna
-
National Cancer Institute (NCI)AvslutadTidigare behandlade myelodysplastiska syndrom | Sekundära myelodysplastiska syndrom | de Novo myelodysplastiska syndromFörenta staterna
-
TJ Biopharma Co., Ltd.Rekrytering
-
National Heart, Lung, and Blood Institute (NHLBI)National Cancer Institute (NCI)RekryteringMyelodysplastiska syndrom (MDS)Förenta staterna, Israel
-
AbbVieCelgene; Genentech, Inc.AvslutadMyelodysplastiska syndrom (MDS)Förenta staterna, Australien, Tyskland
-
AbbVieGenentech, Inc.Aktiv, inte rekryterandeMyelodysplastiska syndrom (MDS)Förenta staterna, Australien, Kanada, Frankrike, Tyskland, Italien, Storbritannien
Kliniska prövningar på Placebo
-
SamA Pharmaceutical Co., LtdOkändAkut bronkit | Akut övre luftvägsinfektionKorea, Republiken av
-
National Institute on Drug Abuse (NIDA)AvslutadAnvändning av cannabisFörenta staterna
-
AstraZenecaParexel; Spandauer Damm 130; 14050; Berlin, GermanyAvslutadManliga försökspersoner med typ II-diabetes (T2DM)Tyskland
-
Heptares Therapeutics LimitedAvslutadFarmakokinetik | SäkerhetsfrågorStorbritannien
-
Texas A&M UniversityNutraboltAvslutadGlucose and Insulin Response
-
Regado Biosciences, Inc.AvslutadFrisk volontärFörenta staterna
-
Longeveron Inc.AvslutadHypoplastiskt vänsterhjärtsyndromFörenta staterna
-
ItalfarmacoAvslutadBeckers muskeldystrofiNederländerna, Italien
-
Universidade Estadual de LondrinaConselho Nacional de Desenvolvimento Científico e Tecnológico; Coordination...AvslutadVassleproteintillskott associerat med motståndsträning på hälsoindikatorer hos tränade äldre kvinnorFriska | Kroppssammansättning