Hypercholesterolemia Clinical Trial in Bethesda MD
NCT00353782
| Observational
This study is looking to recruit 2000 Participants
This study will evaluate people with dyslipidemias - disorders that affect the fat content in
the blood. Fats, or lipids, such as cholesterol and triglycerides, are carried in the blood
in particles called lipoproteins. These particles are involved in causing blood vessel
diseases that can lead to conditions like atherosclerosis (hardening of the arteries) or
heart attack. Participants will undergo accepted medical tests and procedures to evaluate
their condition. Most of the test results are helpful in making a diagnosis and in guiding
treatment.
People with lipid disorders are eligible for this study. Representative types of patients
include those with:
- Plasma cholesterol levels greater than 200 mg/dl or less than 120 mg/dl
- Plasma LDL-C levels greater than 130 mg/dl or less than 70 mg/dl
- Plasma HDL-C levels greater than 70 mg/dl or less than 25 mg/dl
- Unusual cholesterol deposits or xanthomas (nodules of lipid deposits on the skin)
Children under 2 years of age are excluded from the study.
Participants will undergo some or all of the following procedures:
- Plasma evaluation. Apolipoproteins (plasma proteins involved in metabolism of
cholesterol, triglycerides, phospholipids, and proteins in the blood) and enzymes
involved in lipid metabolism are measured.
- Fat biopsy. A small sample of fat tissue is collected for examination. For this test, an
area on the buttock or abdominal wall is numbed. A needle is inserted into the fat, and
a small amount of tissue is sucked out by a syringe.
- Leukapheresis. White blood cells are collected to help diagnose the lipid disorder. For
this test, blood is collected through a needle in an arm vein, similar to donating
blood. The blood circulates through a machine that separates it into its components, and
the white cells are removed. The rest of the blood is returned to the body, either
through the same needle or through another needle in the other arm.
- Skin biopsy. Skin cells are collected for study. The cells are grown in the laboratory
and the amount of cholesterol that enters or leaves the cells is measured, providing
information on abnormalities in cholesterol transport. For this test, an area of skin is
numbed with an anesthetic and a small circular area is removed, using a skin punch
instrument similar to a sharp cookie cutter.
- Heparin infusion study. Heparin, a blood thinner, releases enzymes that break down fat
in the blood. Lipase activity (breakdown of fats) in the blood is measured following the
injection of heparin into a vein.
Details for the study
Brief Title
Causes and Natural History of Dyslipidemias
Official Title
Disease Pathogenesis and Natural History of Lipid Disorders
Brief Summary
This study will evaluate people with dyslipidemias - disorders that affect the fat content in
<br /> the blood. Fats, or lipids, such as cholesterol and triglycerides, are carried in the blood
<br /> in particles called lipoproteins. These particles are involved in causing blood vessel
<br /> diseases that can lead to conditions like atherosclerosis (hardening of the arteries) or
<br /> heart attack. Participants will undergo accepted medical tests and procedures to evaluate
<br /> their condition. Most of the test results are helpful in making a diagnosis and in guiding
<br /> treatment.
<br />
<br /> People with lipid disorders are eligible for this study. Representative types of patients
<br /> include those with:
<br />
<br /> - Plasma cholesterol levels greater than 200 mg/dl or less than 120 mg/dl
<br />
<br /> - Plasma LDL-C levels greater than 130 mg/dl or less than 70 mg/dl
<br />
<br /> - Plasma HDL-C levels greater than 70 mg/dl or less than 25 mg/dl
<br />
<br /> - Unusual cholesterol deposits or xanthomas (nodules of lipid deposits on the skin)
<br />
<br /> Children under 2 years of age are excluded from the study.
<br />
<br /> Participants will undergo some or all of the following procedures:
<br />
<br /> - Plasma evaluation. Apolipoproteins (plasma proteins involved in metabolism of
<br /> cholesterol, triglycerides, phospholipids, and proteins in the blood) and enzymes
<br /> involved in lipid metabolism are measured.
<br />
<br /> - Fat biopsy. A small sample of fat tissue is collected for examination. For this test, an
<br /> area on the buttock or abdominal wall is numbed. A needle is inserted into the fat, and
<br /> a small amount of tissue is sucked out by a syringe.
<br />
<br /> - Leukapheresis. White blood cells are collected to help diagnose the lipid disorder. For
<br /> this test, blood is collected through a needle in an arm vein, similar to donating
<br /> blood. The blood circulates through a machine that separates it into its components, and
<br /> the white cells are removed. The rest of the blood is returned to the body, either
<br /> through the same needle or through another needle in the other arm.
<br />
<br /> - Skin biopsy. Skin cells are collected for study. The cells are grown in the laboratory
<br /> and the amount of cholesterol that enters or leaves the cells is measured, providing
<br /> information on abnormalities in cholesterol transport. For this test, an area of skin is
<br /> numbed with an anesthetic and a small circular area is removed, using a skin punch
<br /> instrument similar to a sharp cookie cutter.
<br />
<br /> - Heparin infusion study. Heparin, a blood thinner, releases enzymes that break down fat
<br /> in the blood. Lipase activity (breakdown of fats) in the blood is measured following the
<br /> injection of heparin into a vein.
Detailed Description
The lipoprotein transport system is vital to the delivery of the hydrophobic fats that are
carried in the aqueous environment of the blood. The lipoprotein particles that comprise this
system are polydisperse and contain triglycerides, free and esterified cholesterol,
phospholipids and proteins. Inborn errors in the lipoprotein transport system lead to
alterations in both the steady state concentrations of the various lipoproteins and in the
metabolism of these particles. These inborn errors lead to both hyperlipoproteinemia and
hypolipoproteinemia. Profound changes in the ambient lipoprotein concentrations have a
variety of clinical manifestations. The present study protocol is designed to permit a full
plasma evaluation of the lipids, lipoproteins and apolipoproteins, in patients with potential
genetic defects in these processes. We will use a variety of research plasma assays. These
specialized plasma assays are necessary to correctly diagnose and treat patients that present
with the more unusual disorders of lipid metabolism; these patients cannot be diagnosed by
standard, CLIA- Certified assays and may require tissue or blood cells for diagnosis and
adequate treatment. The study population will include patients which are referred to the
Lipid Service, Cardiovascular Branch, NHLBI from private care providers, academic
institutions or the NHLBI-MDB website, with any of the following potential lipid
abnormalities or clinical stigmata associated with dyslipoproteinemias: a) increased plasma
levels of cholesterol, triglycerides, HDL-cholesterol or LDL-cholesterol b) decreased plasma
concentrations of cholesterol and HDL-cholesterol c) postprandial hyperlipidemia or d)
eruptive xanthomas, xanthelasma, tuberous or tendinous xanthomas, or corneal opacities.
Outcome Measures
Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.
Primary
permit a full evaluation of the lipoproteins, apolipoproteins, and cellular enzymes and receptors relevant to lipoprotein metabolism in order to accurately diagnose and treat patients with potential genetic defects in these processes
Evaluate Lipids
Study Criteria
INCLUSION CRITERIA:
- Children >= 2 years of age and >12 kg and adults
- Dyslipidemia subjects of interest the group
The following is a representative list of the types of patient presentations with
dyslipidemia and potential diagnoses eligible for this protocol:
- Plasma cholesterol levels >200 mg/dl or <120 mg/dl includes patients with diagnoses
such as familial hypercholesterolemia, familial combined hyperlipidemia,
sitosterolemia, lipoprotein lipase, hepatic lipase or apo-CII deficiency, and
dysbetalipoproteinemia.
- Plasma LDL-C levels >130 mg/dl or <70 mg/dl includes patients with diagnoses such as
familial hypercholesterolemia, PCSK9, apo3500, familial combined hyperlipidemia,
sitosterolemia, dysbetalipoproteinemia, abetalipoproteinemia and
hypobetalipoproteinemia.
- Plasma HDL-C levels >70 mg/dl or <25 mg/dl includes patients with deficiency of
cholesteryl ester transfer protein, lecithin cholesterol acyltransferase, phospholipid
transfer protein, lipoprotein lipase, hepatic lipase, or apo-CII, ANGPTL3, and Tangier
disease.
- Plasma triglyceride levels >150 mg/dl includes patients with deficiency of lipoprotein
lipase, hepatic lipase or apoC-II, GPIHBP1, LMF1, dysbetalipoproteinemia, Type I, Type
IV and Type V hyperlipidemia.