Study of TNF-Antagonism in the Metabolic Syndrome (II)
2010年11月3日 更新者: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.
研究概览
详细说明
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.
研究类型
介入性
注册 (实际的)
40
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
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Massachusetts
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Boston、Massachusetts、美国、02114
- MGH
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参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 60年 (成人)
接受健康志愿者
不
有资格学习的性别
全部
描述
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
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
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安慰剂比较:安慰剂
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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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有源比较器:依那西普
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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
其他名称:
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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C-reactive Protein (CRP)
大体时间:6 months
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As a measure of C-reactive protein (CRP), which is an inflammatory marker, Log10 of the CRP at 6 months is reported
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6 months
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Interleukin-6 (IL-6)
大体时间:6 months
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6 month value of IL-6 (pg/mL)
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6 months
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Adiponectin
大体时间:6 months
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The ratio of circulating high molecular weight (HMW) adiponectin to total adiponectin ratio (HMW:total Adiponectin) at 6 months is reported.
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6 months
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Glucose Tolerance
大体时间:6 months
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Fasting glucose (mg/dL) at 6mo
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6 months
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Endothelial Function
大体时间:6 months
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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.
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6 months
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White Blood Cell (WBC) Count
大体时间:Baseline to 6 months
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Change in WBC during study (WBC at six months minus WBC at baseline)
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Baseline to 6 months
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Cardiac Echo Ejection Fraction (EF)
大体时间:Baseline to 6 months
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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.
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Baseline to 6 months
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Body Composition
大体时间:6 months
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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
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6 months
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Tumor Necrosis Factor (TNF) Receptor
大体时间:6 months
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Circulating concentrations of Tumor necrosis factor receptor 2 (TNFR2) at 6 months
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6 months
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Other Adipocytokines
大体时间:6 months
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circulating resistin at 6 months
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6 months
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Lipid Levels
大体时间:6 months
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total cholesterol (mg/dL) at 6 months
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6 months
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Adipocyte Messenger Ribonucleic Acid (mRNA) Levels of Adipocytokines Including Tumor Necrosis Factor (TNF) -Alpha
大体时间:6 months
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fold-change in subcutaneous adipose tissue expression of TNF-alpha (mRNA) after 6 months
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6 months
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始
2006年12月1日
初级完成 (实际的)
2009年9月1日
研究完成 (实际的)
2009年9月1日
研究注册日期
首次提交
2006年12月7日
首先提交符合 QC 标准的
2006年12月18日
首次发布 (估计)
2006年12月19日
研究记录更新
最后更新发布 (估计)
2010年12月2日
上次提交的符合 QC 标准的更新
2010年11月3日
最后验证
2010年11月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
代谢综合征的临床试验
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Sanford HealthNational Ataxia Foundation; Beyond Batten Disease Foundation; Pitt Hopkins Research Foundation; Cornelia... 和其他合作者招聘中线粒体疾病 | 色素性视网膜炎 | 重症肌无力 | 嗜酸性胃肠炎 | 多系统萎缩 | 平滑肌肉瘤 | 脑白质营养不良 | 肛瘘 | 脊髓小脑性共济失调3型 | 弗里德赖希共济失调 | 肯尼迪病 | 莱姆病 | 噬血细胞性淋巴组织细胞增生症 | 脊髓小脑性共济失调1型 | 脊髓小脑性共济失调2型 | 脊髓小脑共济失调6型 | 威廉姆斯综合症 | 先天性巨结肠症 | 糖原贮积病 | 川崎病 | 短肠综合症 | 低磷血症 | Leber先天性黑蒙 | 口臭 | 贲门失弛缓症 | 多发性内分泌肿瘤 | 利综合症 | 艾迪生病 | 多发性内分泌肿瘤 2 型 | 硬皮病 | 多发性内分泌肿瘤 1 型 | 多发性内分泌肿瘤 2A 型 | 多发性内分泌肿瘤 2B 型 | 非典型溶血性尿毒症综合征 | 胆道闭锁 | 痉挛性共济失调 | WAGR综合症 | 无虹膜 | 短暂性失忆症 | 马尾综合症 | Refsum 疾病 | 复发性呼吸... 及其他条件美国, 澳大利亚
Placebo的临床试验
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City of Hope Medical CenterNational Cancer Institute (NCI)主动,不招人造血和淋巴细胞肿瘤 | 骨髓纤维化 | 慢性淋巴细胞白血病 | 缓解期成人急性髓性白血病 | 骨髓增生异常综合症 | 缓解期成人急性淋巴细胞白血病 | 骨髓增殖性肿瘤 | 慢性期慢性粒细胞白血病,BCR-ABL1 阳性 | 成人淋巴母细胞淋巴瘤 | 加速期慢性粒细胞白血病,BCR-ABL1 阳性 | HLA-A*0201 阳性细胞存在 | 巨细胞病毒感染 | 成人霍奇金淋巴瘤 | 成人非霍奇金淋巴瘤美国
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Mila (bMotion Technologies)完全的
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Universidad Autonoma de MadridCentro Universitario La Salle完全的