4 Clinical Trials for Various Conditions
This study will test the safety and effectiveness of 40 mg of ezetimibe (Zetia ) daily in lowering blood levels of cholesterol and of the plant sterols sitosterol and campesterol in patients with homozygous sitosterolemia, an inherited disorder of sterol metabolism. (Sterols are alcohol substances found in animal and plant fats.) In this disorder, an excess of many plant sterols is absorbed and not enough excreted. Patients can develop atherosclerosis and coronary heart disease as early as childhood, as well as other problems including arthritis, arthralgia, and tendon xanthomas (lipid deposits). Current treatment consists of ezetimibe 10 mg, dietary restriction of plant and shellfish sterols, and bile salt binding resins. Ezetimibe is a cholesterol-lowering drug that inhibits intestinal absorption of cholesterol and structurally related plant sterols across the intestinal wall. Patients with homozygous sitosterolemia who are between 18 and 85 years of age have completed NHLBI's 1-year study of ezetimibe at 10 mg a day may be eligible for this study. All participants maintain their current stable diet and take a 10-mg pill of ezetimibe daily for 26 weeks. They are also randomly selected to take either an additional 30-mg pill of ezetimibe or a placebo (look-alike pill with no active ingredients). Patients fast for at least 12 hours before each of 6 visits scheduled during the course of the study. At these visits, patients undergo some or all of the following procedures for monitoring their health and evaluating their response to treatment: * Medical history and review of medications * Physical examination * Measurement of vital signs (pulse rate, blood pressure, breathing rate and temperature) * Review of dietary maintenance * Measurements of height, weight, and waist circumference * Measurement (with ruler) and photographs of non-Achilles xanthoma * X-ray of Achilles tendon * Blood draw and urine collection * Pregnancy test for women of childbearing potential
OBJECTIVES: I. Identify the genetic defect and fine map the gene that causes sitosterolemia.
This study will test the safety and effectiveness of SCH-58235 (Ezetimibe) in lowering sitosterol, plant sterol and cholesterol blood levels in patients with homozygous sitosterolemia when added to the patients' current treatment regimen. Homozygous sitosterolemia is an inherited disorder of sterol metabolism in which an excess of many plant sterols, including sitosterol, is absorbed and not enough excreted. (Sterols are substances used to form hormones, vitamins and membranes found in animal and plant lipids.). Patients can develop atherosclerosis with coronary heart disease as early as childhood, as well as other problems including arthritis, arthralgia, and tendon xanthomas (lipid deposits). Current sitosterolemia treatments may include a low sterol diet, medications, intestinal surgery, or a combination of these. Ezetimibe is a member of a new class of drugs called "specific cholesterol absorption inhibitors" that may lower cholesterol, sitosterol and other plant sterol blood levels. Patients with homozygous sitosterolemia 10 years of age and older may be eligible for this study. Participants will have a medical history and physical examination and will be randomly assigned to one of two treatment groups. One group, which will include about 80 percent of all study participants, will take 10 mg of Ezetimibe a day, and the second group (20 percent of participants) will take a placebo (an inactive look-a-like pill). Patients will have 7 clinic visits during the 12-week study, when some or all of the following procedures and tests will be done: * Measurement of vital signs (heart rate, blood pressure, breathing rate and temperature) * Dietary maintenance - interview about how well that patient is adhering to the diet * Medication review - interview about other medications the patient is taking * Blood draw for tests * Urine sample for tests * Pregnancy test for women of childbearing potential * Electrocardiogram (ECG) to measure the electrical activity of the heart * Blood draw to determine sitosterol, other plant sterol levels, and lipid levels (cholesterol and other blood lipid concentrations) * Xanthoma measurement (with a ruler and X-ray of the foot)
This study will determine if dietary supplements of sitosterol (a plant cholesterol commonly found in vegetables) can modify blood sugar and cholesterol levels and reduce the stiffness of the blood vessels in people with an abnormal copy of a gene that causes sitosterolemia. People who carry only one copy of the abnormal gene are healthy but have increased blood levels of sitosterol. People with two abnormal copies of the gene have increased levels of sitosterol and have an increased risk of heart attack. This condition is called sitosterolemia. Although extremely rare in the general population, up to 4% of the Amish carry an abnormal copy of this gene. People of Amish background who are 18 years of age or older and in whom one person carries one copy of the abnormal gene that causes sitosterolemia and the other does not have an abnormal gene may be eligible for this study. Subjects must be of the same sex and within 5 years of age of each other. During two periods of one month each participants receive pills containing sitosterol and then a special diet and meal supplements to change the levels of sitosterol in the diet. During only one of the two study periods, subjects receive sitosterol supplements in the pills for one month and then for 10 days in the diet. At the end of each study period, subjects come to the NIH Clinical Center for one day for the following tests: * Measurements of height, weight, blood pressure and heart rate. * Adipose (fat) tissue biopsy. A small piece of fat from under the skin of the abdomen is removed to examine how sitosterol affects fat tissue and its ability to process sugar and fat. * Indirect calorimetry. A plastic transparent hood is placed over the subject s head to collect the air that is breathed for about one-half hour to study how the body uses sugar to generate energy. * Endothelial vascular function. An ultrasound picture of a blood vessel in the forearm is taken and a blood pressure cuff is inflated around the arm to measure the vessel s ability to stretch. * Intravenous glucose tolerance test: A small plastic tube is placed in a vein in each arm. Then over one minute the subject receives glucose through one of the tubes. Twenty minutes later the subject is given a small amount of insulin through the same tube. Blood samples are drawn through the tube in the other arm at frequent intervals for 3 hours. This test measures how sitosterol affects how the body processes sugar. * DEXA scan. The subject lies on an x-ray table for 20 minutes during the scan, which measures total body fat.