Higher-Dose Ezetimibe to Treat Homozygous Sitosterolemia

NCT00099996 | Completed Phase 3

• 2 other identifiers: 05006005-H-0060
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Heart Diseases; Metabolism, Inborn Errors

Keywords

Sitosterolemia; Sitosterol; Ezetimibe; Absorption; Intestine; Cholesterol; Atherosclerosis; Homozygous Sitosterolemia

Interventions

SCH-58235 DRUG

Ezetimibe DRUG

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• To be enrolled into this study, patients must meet all of the following criteria:
• Patient is at least 18 years of age and no greater than 85 years of age as of Visit 1.
• Patient has a diagnosis of homozygous sitosterolemia, with a history of a plasma sitosterol concentration greater than 5 mg/dL (0.13 mmol/L).
• Patient has been on an ongoing stable regimen of ezetimibe 10 mg daily for at least 6 months prior to Visit 1.
• If patient is currently on a treatment for sitosterolemia (in addition to ezetimibe 10 mg), treatment regimen must be stable for at least 4 weeks prior to visit 1.
• Note: Treatments may include bile salt binding resins, statins, and/or apheresis.
• Patient must be willing to maintain their current treatment regimen for the duration of the study.
• Patient must be on a stable diet for at least 4 weeks prior to visit 1.
• Patient must be willing to maintain this diet for the duration of the study.
• Patient is a man or postmenopausal woman. Patient is a premenopausal woman who is either surgically sterilized or highly unlikely to conceive, and has a negative urine beta-hCG pregnancy test within 72 hours prior to the start of study treatment.
• Note: Highly unlikely to conceive is defined as a woman who: (1) has vasectomized partners, or (2) has a copper intrauterine device (IUD) in place for greater than 3 months without complaint, or (3) abstains from heterosexual intercourse, or (4) agrees to use a double-barrier method of contraception, or (5) is using noncyclical oral contraceptive.

You may not qualify if:

• Patient has a condition which, in the opinion of the investigator, might pose a risk to the patient, interfere with participation in the study, or does not meet criteria for this protocol.
• MEDICAL HISTORY AND LABORATORY ABNORMALITIES PRIOR TO RANDOMIZATION:
• Patient has clinically significant laboratory abnormalities at visit 1 and/or last available laboratory results prior to visit 2:
• i. ALT (SGPT) greater than or equal to 3 x ULN (75 mU/mL or 75 IU/L).
• ii. AST (SGOT) greater than or equal to 3 x ULN (66 mU/mL or 66 IU/L).
• iii. TSH greater than 6 microIU/mL or 6mIU/L - or change in medication for hypothyroidism within 6 weeks prior to visit 1.
• iv. CPK greater than or equal to 3 x ULN (360 mg/dL or 360 IU/L) and persistent elevation at redraw with muscle symptoms consistent with myopathy.
• c. Patient has known hypersensitivity of contraindication to ezetimibe.
• d. Patient is breast feeding.
• e. Patient's weight is less than 40 kg.
• f. Patient has been treated with any other investigational drug within 30 days prior to visit 1.
• PROHIBITED MEDICAL CONDITIONS:
• g. Patient has uncontrolled cardiac arrhythmias.
• h. Patient has had unstable angina pectoris within 1 month of visit 1.
• i. Patient has severe/unstable peripheral vascular disease.

Sponsors & Collaborators

• National Heart, Lung, and Blood Institute (NHLBI): lead

Study Sites (1)

National Heart, Lung and Blood Institute (NHLBI)

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Bhattacharyya AK, Connor WE. Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters. J Clin Invest. 1974 Apr;53(4):1033-43. doi: 10.1172/JCI107640.

  PMID: 4360855 BACKGROUND

• Salen G, Shefer S, Nguyen L, Ness GC, Tint GS, Shore V. Sitosterolemia. J Lipid Res. 1992 Jul;33(7):945-55.

  PMID: 1431587 BACKGROUND

• Salen G, Horak I, Rothkopf M, Cohen JL, Speck J, Tint GS, Shore V, Dayal B, Chen T, Shefer S. Lethal atherosclerosis associated with abnormal plasma and tissue sterol composition in sitosterolemia with xanthomatosis. J Lipid Res. 1985 Sep;26(9):1126-33.

  PMID: 4067433 BACKGROUND

MeSH Terms

Conditions

Heart Diseases; Metabolism, Inborn Errors; Sitosterolemia; Atherosclerosis

Interventions

Ezetimibe

Condition Hierarchy (Ancestors)

Cardiovascular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolic Diseases; Nutritional and Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Vascular Diseases

Intervention Hierarchy (Ancestors)

Azetidines; Azetines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Design

• Study Type: interventional
• Phase: phase 3
• Purpose: TREATMENT
• Sponsor Type: NIH

Study Record Dates

• First Submitted: December 21, 2004
• First Posted: December 22, 2004
• Study Start: December 1, 2004
• Study Completion: December 1, 2005
• Last Updated: March 4, 2008

Record last verified: 2005-12

Locations

US (1)