The Effect of Dietary Sitosterol on Blood Sugar and Cholesterol

NCT00531128 | Completed

• 2 other identifiers: 07021907-DK-0219
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 2

Brief 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. 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.

Conditions

Sitosterolemia

Keywords

Sitosterol; Nutrigenomics; Gene Expression; Insulin Resistance; Sitosterolemia

Outcome Measures

Primary Outcomes (1)

• Circulating lipids, glucose disposal, energy expenditure.

Secondary Outcomes (1)

• Endothelial vascular function, adipose tissue gene expression.

Interventions

High/Low Sitosterol BEHAVIORAL

Eligibility Criteria

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

You may qualify if:

• Age greater than or equal to 18 years, male or female
• Genotype ABCG8: G574 (case) or R574 (control)
• Amish ethnicity (as self-described and from the Fisher's Book)
• Informed consent (obtained in the presence of the Amish Liaison nurse)
• Control person: same sex and age +/- 5 years from case

You may not qualify if:

• 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
• 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)

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): lead

Study Sites (2)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

University of Maryland Amish Research

Lancaster, Pennsylvania, United States

Location

Related Publications (3)

• 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. doi: 10.2337/diabetes.50.3.686.

  PMID: 11246892 BACKGROUND

• 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. doi: 10.1055/s-2003-39475.

  PMID: 12778362 BACKGROUND

• von Bergmann K, Sudhop T, Lutjohann D. Cholesterol and plant sterol absorption: recent insights. Am J Cardiol. 2005 Jul 4;96(1A):10D-14D. doi: 10.1016/j.amjcard.2005.03.014.

  PMID: 15992510 BACKGROUND

MeSH Terms

Conditions

Sitosterolemia; Insulin Resistance

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Study Officials

• Kong Y Chen, Ph.D.

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Purpose: PREVENTION
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 14, 2007
• First Posted: September 18, 2007
• Study Start: September 10, 2007
• Primary Completion: July 27, 2012
• Study Completion: May 17, 2018
• Last Updated: May 21, 2018

Record last verified: 2018-05-17

Locations

US (2)