DIET/EXERCISE, NIACIN, FENOFIBRATE FOR HIV LIPODYSTROPHY
饮食/运动、烟酸、非诺贝特治疗 HIV 脂肪代谢障碍
基本信息
- 批准号:8356764
- 负责人:
- 金额:$ 0.18万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-12-01 至 2011-11-30
- 项目状态:已结题
- 来源:
- 关键词:AbdomenAdipose tissueBehavior TherapyBody fatCentral obesityCholesterolCholesterol EstersClinical ResearchDataDyslipidemiasFastingFatty acid glycerol estersFenofibrateFundingGlucoseGrantHIVHepaticHigh Density Lipoprotein CholesterolHigh Density LipoproteinsHighly Active Antiretroviral TherapyHormonalHypertriglyceridemiaInsulinInsulin ResistanceInterventionKineticsLDL Cholesterol LipoproteinsLeptinLipidsLipoatrophyLipodystrophyLipolysisLipoproteinsLow-Density LipoproteinsMeasuresMetabolicMetabolic MarkerNational Center for Research ResourcesNicotinic AcidsNonesterified Fatty AcidsPatientsPatternPlacebo ControlPlasmaPrincipal InvestigatorProteinsRecommendationRecruitment ActivityRegimenResearchResearch InfrastructureResourcesSourceTimeTreatment ProtocolsTriglyceridesUnited States National Institutes of HealthVisceralX-Ray Computed Tomographybasecardiovascular disorder riskcardiovascular risk factorcostdiet and exerciseeffective therapyevidence basefatty acid oxidationimprovedlifestyle interventionrandomized placebo controlled trialsubcutaneoustreatment as usual
项目摘要
This subproject is one of many research subprojects utilizing the resources
provided by a Center grant funded by NIH/NCRR. Primary support for the subproject
and the subproject's principal investigator may have been provided by other sources,
including other NIH sources. The Total Cost listed for the subproject likely
represents the estimated amount of Center infrastructure utilized by the subproject,
not direct funding provided by the NCRR grant to the subproject or subproject staff.
ABSTRACT
HYPOTHESIS
In HIV patients with HAART-associated dyslipidemia , an intensive lifestyle intervention with diet and exercise can:
A. Convert the lipid profile from atherogenic to cardioprotective;
B. Decrease abdominal visceral fat mass;
C. Improve hormonal, metabolic and lipoprotein markers associated with insulin resistance.
SPECIFIC AIMS
1. To compare the effects of 1) usual care, 2) intensive diet and exercise intervention (DE), 3) DE + niacin, 4) DE + fenofibrate, and 5) DE + niacin + fenofibrate on fasting plasma triglyceride concentrations (Primary endpoint).
(To achieve this Aim, we will recruit 240 HIV patients with hypertriglyceridemia who are on stable HAART regimens. We will assign them randomly to the five placebo-controlled treatment protocols (48 per group) and measure fasting plasma concentrations of triglycerides (primary lipid endpoint) as well as fasting plasma concentrations of HDL cholesterol, total cholesterol and LDL cholesterol (secondary lipid endpoints) at baseline and after 6 months of intervention.)
2. To compare the effects of the five treatment protocols on body fat distribution.
(To achieve this Aim, we will measure, in the same subjects and at the same time points, regional fat distribution (ratio of abdominal visceral adipose mass to subcutaneous adipose mass) using computerized tomography.)
3. To compare the effects of the five treatment protocols on hormonal, lipoprotein and metabolic markers of insulin resistance.
(To achieve this Aim, we will measure, in the same subjects, changes in the plasma concentrations of insulin, glucose, leptin, free fatty acids, and LDL and HDL subfractions, in the compositions of LDL and HDL, and in the activity of cholesteryl ester transfer protein.)
BACKGROUND AND SIGNIFICANCE
Highly active anti-retroviral therapy (HAART) is associated with dyslipidemia and insulin resistance in a large proportion of HIV-infected patients, and with anthropomorphic changes (lipoatrophy, central obesity) in a smaller subset. The dyslipidemia and insulin resistance place these patients at increased risk for cardiovascular disease. The mechanisms leading to the dyslipidemia, insulin resistance and anthropomorphic changes - collectively termed "HIV-lipodystrophy" - have been unclear. Numerous small studies have failed to delineate a course of therapy that can clearly reverse the dyslipidemia and attendant cardiovascular risk in the majority of patients. There is an urgent need for evidence-based, rational, effective therapy of this condition.
Based on 1) our recent data on key mechanisms of altered lipid kinetics in HIV-lipodystrophy (specifically, elevated rates of lipolysis, inadequate fatty acid oxidation, and increased hepatic reesterification of triglycerides); 2) evidence that diet and exercise patterns of HIV patients are suboptimal to manage cardiovascular risk factors; and 3) the latest treatment recommendations for dyslipidemia and insulin resistance, we propose a randomized, placebo-controlled trial of intensive lifestyle modification and two lipid-lowering agents (niacin and fenofibrate).
The long-term objective is to develop effective, safe, rational treatment of HIV-associated dyslipidemia and lipodystrophy.
该副本是利用资源的众多研究子项目之一
由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持
而且,副投影的主要研究员可能是其他来源提供的
包括其他NIH来源。 列出的总费用可能
代表subproject使用的中心基础架构的估计量,
NCRR赠款不直接向子弹或副本人员提供的直接资金。
抽象的
假设
在患有HAART相关血脂异常的HIV患者中,对饮食和运动的强化生活方式干预可以:
答:将脂质谱从动脉粥样硬化转换为心脏保护;
B.减少腹部内脏脂肪量;
C.改善与胰岛素抵抗相关的激素,代谢和脂蛋白标记。
具体目标
1。为了比较1)通常的护理,2)强化饮食和运动干预(DE),3)DE +烟酸,4)De + Fenodribrate和5)DE +烟酸 +烟酸 + fenofirtart对禁食等离子体甘油三酸酯浓度(主要端点)。
(To achieve this Aim, we will recruit 240 HIV patients with hypertriglyceridemia who are on stable HAART regimens. We will assign them randomly to the five placebo-controlled treatment protocols (48 per group) and measure fasting plasma concentrations of triglycerides (primary lipid endpoint) as well as fasting plasma concentrations of HDL cholesterol, total cholesterol and LDL cholesterol (secondary脂质终点)在基线和干预6个月后。)
2。比较五种治疗方案对人体脂肪分布的影响。
(为了实现这一目标,我们将使用计算机断层扫描中的区域脂肪分布(腹部内脏脂肪质量与皮下脂肪质量的比率)在相同的受试者中测量。)
3。比较五种治疗方案对胰岛素抵抗激素,脂蛋白和代谢标记的影响。
(为了实现这一目标,我们将在相同的受试者中测量胰岛素,葡萄糖,瘦素,游离脂肪酸,LDL和HDL亚晶状体的血浆浓度的变化,在LDL和HDL的组成中,以及胆固醇酯转移蛋白的活性。
背景和意义
高度活跃的抗返回病毒疗法(HAART)与较大的较小子集中的艾滋病毒感染患者(HAART)与大量的HIV感染患者以及拟人化变化(脂肪植物,中央肥胖症)有关。血脂异常和胰岛素抵抗使这些患者患心血管疾病的风险增加。导致血脂异常,胰岛素抵抗和拟人化变化的机制尚不清楚。 许多小型研究未能描绘出可以清楚地扭转大多数患者血脂异常和随随之致的心血管风险的治疗方法。迫切需要对这种情况进行基于证据的,理性的,有效的治疗。
基于1)我们最近有关HIV脂营养不良脂质脂质脂质脂动力学改变的关键机制的数据(具体而言,脂解的速率升高,脂肪酸氧化不足以及甘油三甘油三酸酯的肝脏重新酯化的增加); 2)证据表明,艾滋病毒患者的饮食和运动模式是管理心血管危险因素的次优。 3)关于血脂异常和胰岛素抵抗的最新治疗建议,我们提出了一项随机的,安慰剂对照的强化生活方式修饰的试验和两种降低脂质的剂(烟酸和fenofibrate)。
长期目标是开发与HIV相关血脂异常和脂肪营养不良的有效,安全,合理的治疗。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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ASHOK BALASUBRAMANYAM其他文献
ASHOK BALASUBRAMANYAM的其他文献
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{{ truncateString('ASHOK BALASUBRAMANYAM', 18)}}的其他基金
Center for Identification and Study of Individuals with Atypical Diabetes Mellitus (U54)
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Role of Islet Injury and Autoimmunity in T2D Beta Cell Dysfunction
胰岛损伤和自身免疫在 T2D β 细胞功能障碍中的作用
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