Protocol Number: 07-DK-0219

Title:

A Nutrigenomics Intervention for the Study of the Role of Dietary Sitosterol on Lipid, Glucose and Energy Metabolism

Number:

07-DK-0219

Summary:

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.

Siblings of Amish background who are 18 years of age or older and in whom one sibling 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. Siblings must be of the same sex and within 8 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.

Sponsoring Institute:

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: No

Population Exclusion(s): Children

American Indian or Alaskan Native

Asian

Black (Not of Hispanic Origin)

Hispanic

Pacific Islander

Eligibility Criteria:

INCLUSION CRITERIA:

-Age greater than or equal to 18 years, male or female

-Genotype ABCG8: G574 (case) or R574 (control sib)

-Amish ethnicity (as self-described and from the Fisher's Book)

-Informed consent (obtained in the presence of the Amish Liaison nurse)

-Control sib: same sex and age greater than or equal to 8 years from case

EXCLUSION CRITERIA:

-BMI greater than or equal to 40 kg/m(2)

-History or symptoms compatible with cardiovascular disease, including hypertension greater than or equal to 140/90 mm Hg or current therapy for hypertension or cardiovascular disease

-Allergy to lidocaine, acetaminophen with codeine, oxycodone.

-Pregnancy

-Breastfeeding

-Use of hormonal contraceptives or estrogen replacement therapy

-Use of tobacco (smoking, chewing) during the study, including the period of outpatient dietary intervention

-Diabetes mellitus, either type 1 or 2

-Hypercholesterolemia (serum levels greater than or equal to 240 mg/dL), and/or use of antilipemic therapy

-Liver disease or ALT serum level greater than two fold the upper laboratory reference limit

-Renal insufficiency or estimated creatinine clearance less than or equal to 50 mL/min

-Use of medications/dietary supplements/alternative therapies known or thought to alter lipid or carbohydrate metabolism (e.g. omega-3 fatty acids, chromium, vanadate) during the study

-Current history or symptoms compatible with psychosis including major depression (including history of hospitalization for depression, history of attempted suicide, history of suicidal ideation), and/or use of antipsychotic medications

-History of drug or alcohol abuse within the last 5 years; current use of drugs or alcohol (CAGE greater than 3)

-Keloid formation (relative to subcutaneous adipose tissue biopsy)

Special Instructions:

Currently Not Provided

Keywords:

Sitosterol

Nutrigenomics

Gene Expression

Insulin Resistance

Recruitment Keyword(s):

Sitosterolemia

Condition(s):

Sitosterolemia

Investigational Drug(s):

None

Investigational Device(s):

None

Intervention(s):

Behavioral: High/Low Sitosterol

Supporting Site:

National Institute of Diabetes and Digestive and Kidney Diseases

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

Luan J, Browne PO, Harding AH, Halsall DJ, O'Rahilly S, Chatterjee VK, Wareham NJ. Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes. 2001 Mar;50(3):686-9.

Dugail I, Le Lay S, Varret M, Le Liepvre X, Dagher G, Ferre P. New insights into how adipocytes sense their triglyceride stores. Is cholesterol a signal? Horm Metab Res. 2003 Apr; 35(4):204-10. Review.

von Bergmann K, Sudhop T, Lutjohann D. Cholesterol and plant sterol absorption: recent insights. Am J Cardiol. 2005 Jul 4;96(1A):10D-14D. Review.

• Questions about participating in a study, please contact the Patient Recruitment and Public Liaison Office, CC.
• Technical questions regarding the Clinical Center web site, please contact the Department of Clinical Research Informatics, CC.

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