Advertisement

Topics

A Mechanistic Study of the Effects of LY518674 on High-Density Lipoprotein Cholesterol (HDL-C) Metabolism

2014-08-27 03:44:33 | BioPortfolio

Summary

Agents that increase HDL-C via reverse cholesterol transport could provide a new therapeutic option for the prevention of atherosclerotic cardiovascular disease. The investigators propose to investigate the effects of LY518674 on components that may likely affect atherogenesis in patients with the metabolic syndrome including HDL-C metabolism and reverse cholesterol transport pathways, the inflammatory response, and oxidative stress in human subjects.

As an agonist of the nuclear peroxisome proliferator activated receptor (PPAR) alpha, LY518674 may affect the transcription of genes that encode various proteins involved in atherogenesis. This study will explore the consequences of altered transcription such as changes in messenger ribonucleic acid (mRNA) and protein levels as well as protein activity.

Description

Study Objectives

I. Primary Objective:

- To determine the effects of LY518674 on the Apo A-I production rate (calculated from the fractional synthetic rate and the fractional catabolic rate) in subjects with the metabolic syndrome and low HDL-C.

II. Secondary Objectives:

- To determine the effects of LY518674 on markers of reverse cholesterol transport by analyzing changes in serum cholesterol efflux capacity (an in vitro cell-based assay).

- To determine the effects of LY518674 on the activity of lecithin cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), lipoprotein lipase, hepatic lipase, and endothelial lipase.

- To determine the effects of LY518674 on plasma lipids, lipid subfractions, free fatty acids, and the free fatty acid metabolite, beta-OH butyrate.

- To determine the effects of LY518674 on high-density lipoprotein (HDL), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) particle size using nuclear magnetic resonance (NMR).

- To determine the effects of LY518674 on Apo A-II and Apo B-100 kinetics.

- To determine the effects of LY518674 on hsCRP.

- To determine the safety and tolerability of LY518674

Study Design:

Study H8D-MC-EMBG is a single site, randomized, placebo-controlled, double-blind, parallel study. A minimum of 40 subjects with low HDL cholesterol and metabolic syndrome will be randomized to receive double-blind administration of LY518674 100 mcg/day or placebo for 8 weeks. There is a safety visit every 2 weeks after treatment has been initiated, resulting in 7 visits over 10 weeks. There are 2 inpatient visits at zero and eight weeks.

Study Design

Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Conditions

Metabolic Syndrome X

Intervention

LY518674

Location

John Millar
Philadelphia
Pennsylvania
United States
19104

Status

Completed

Source

University of Pennsylvania

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:44:33-0400

Clinical Trials [1625 Associated Clinical Trials listed on BioPortfolio]

Development of Metabolic Syndrome in Children and Adolescents With Leukemia and Lymphomas

The research is devoted to studying the features of the metabolic syndrome in cancer survivors in childhood is supposed to answer the following questions: - How can metabolic syndrome ...

Hämeenlinna Metabolic Syndrome Research Program: Oxidized LDL and Arterial Elasticity in Metabolic Syndrome and Controls (HMS-01)

Mechanisms that link metabolic syndrome to atherosclerosis are incompletely understood. As a part of Hämeenlinna Metabolic Syndrome Research Program (HMS), 40 men with metabolic syndrome...

The Effects of Peroxisome Proliferators Activated Receptor-Gamma (PPAR-γ) Agonists on Certain Biochemical and Inflammatory Markers in Metabolic Syndrome

Metabolic syndrome, labeled as the world's latest epidemic, is the force behind the global epidemic of Type 2 Diabetes Mellitus and Cardio Vascular Diseases. This emerging epidemic is an i...

Frequency of Metabolic Syndrome in Down Syndrome Patients

The aim of this study is to assess the frequency of metabolic syndrome in Down syndrome patients because the prevalence of diabetes mellitus and obesity is higher in individuals with Down ...

Metabolic Syndrome as Consequence of Lipodystrophy Syndrome

To evaluate the prevalence of metabolic syndrome in HIV-infected patients with previous evaluation of lipodystrophy syndrome, according to the severity of fat accumulation and antiretrovir...

PubMed Articles [8327 Associated PubMed Articles listed on BioPortfolio]

Metabolic syndrome among residents of Mizan-Aman town, South West Ethiopia, 2017: A cross sectional study.

Globally, it is estimated that around 20-25% adult population has metabolic syndrome. Individuals who have metabolic syndrome are up to five times more susceptible for chronic diseases than those who ...

Normal body mass index (BMI) can rule out metabolic syndrome: An Israeli cohort study.

The aim of the study was to assess whether body mass index (BMI) can be used as a simple and reliable survey test for metabolic syndrome.The study is an observational cohort study among patients who v...

Not All Clots Are Created Equal: A Review of Deficient Thrombolysis with Tissue Plasminogen Activator (tPA) in Patients with Metabolic Syndrome.

Metabolic syndrome is a cluster of cardiovascular risk factors associated with a prothrombotic, proinflammatory and hypofibrinolysis state. Although resistance to tissue plasminogen activator (tPA) in...

Metabolic Syndrome and Insulin Resistance Syndrome among Infertile Women with Polycystic Ovary Syndrome: A Cross-Sectional Study from Central Vietnam.

Polycystic ovarian syndrome (PCOS) is one of the most common endocrinopathies among reproductive-age women. Its metabolic features often overlap with those associated with metabolic syndrome (MS) and ...

The impact of bariatric surgery on asthma control differs among obese individuals with reported prior or current asthma, with or without metabolic syndrome.

Both obesity and the metabolic syndrome have been independently associated with increased asthma morbidity. However, it is unclear whether metabolic syndrome limits the beneficial effects of weight lo...

Medical and Biotech [MESH] Definitions

A cluster of metabolic risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome X include excess ABDOMINAL FAT; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state. (from AHA/NHLBI/ADA Conference Proceedings, Circulation 2004; 109:551-556)

A cluster of symptoms that are risk factors for CARDIOVASCULAR DISEASES and TYPE 2 DIABETES MELLITUS. The major components of metabolic syndrome include ABDOMINAL OBESITY; atherogenic DYSLIPIDEMIA; HYPERTENSION; HYPERGLYCEMIA; INSULIN RESISTANCE; a proinflammatory state; and a prothrombotic (THROMBOSIS) state.

ANGINA PECTORIS or angina-like chest pain with a normal coronary arteriogram and positive EXERCISE TEST. The cause of the syndrome is unknown. While its recognition is of clinical importance, its prognosis is excellent. (Braunwald, Heart Disease, 4th ed, p1346; Jablonski Dictionary of Syndromes & Eponymic Diseases, 2d ed). It is different from METABOLIC SYNDROME X, a syndrome characterized by INSULIN RESISTANCE and HYPERINSULINEMIA, that has increased risk for cardiovascular disease.

A condition of metabolic imbalance that is caused by complications of initially feeding a severely malnourished patient too aggressively. Usually occurring within the first 5 days of refeeding, this syndrome is characterized by WATER-ELECTROLYTE IMBALANCE; GLUCOSE INTOLERANCE; CARDIAC ARRHYTHMIAS; and DIARRHEA.

Acquired or inborn metabolic diseases that produce brain dysfunction or damage. These include primary (i.e., disorders intrinsic to the brain) and secondary (i.e., extracranial) metabolic conditions that adversely affect cerebral function.

More From BioPortfolio on "A Mechanistic Study of the Effects of LY518674 on High-Density Lipoprotein Cholesterol (HDL-C) Metabolism"

Advertisement
Quick Search
Advertisement
Advertisement

 

Relevant Topics

Cardiology
Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Statins
Statins (or HMG-CoA reductase inhibitors) are a class of drug used to lower cholesterol levels by inhibiting the enzyme HMG-CoA reductase, which plays a central role in the production of cholesterol in the liver. Increased cholesterol levels have been as...


Searches Linking to this Trial