Trial record 12 of 3087 for:    cholesterol

Intralumenal Effects on Cholesterol Absorption/Synthesis

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00328211
First received: May 18, 2006
Last updated: December 5, 2013
Last verified: December 2013
  Purpose

The overall goal of this study is to better understand how cholesterol is absorbed and utilized in the body(metabolism) and how serum cholesterol affects the development of hardening of the arteries (atherosclerosis). The purpose of aim 1 is to assess the role of the amount of different bile acids in the intestine and how they affect the absorption, synthesis and digestion of cholesterol. The effect that these bile acids have on how fast the gall bladder empties and the release of a hormone in the blood after a meal will also be studied. The purpose of aim 2 is to assess the role of phospholipid (a fat containing the element phosphorus) in the intestine and how it affects the absorption, synthesis and digestion of cholesterol in normal people and in people with a genetic condition (mdr3 deficiency)that affects phospholipid and bile acid metabolism. The purpose of aim 3 is to assess the role of a material that acts like a detergent called Pluronic F-68 which is known to block the absorption of cholesterol. The purpose of aim 4 is to determine if the cholesterol from food and the cholesterol made by the body are digested and absorbed differently.


Condition Intervention
Healthy
Dietary Supplement: Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic)
Dietary Supplement: Sphingomyelin
Drug: Pluronic F-68
Other: C13 Stable isotope of Cholesterol

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: Intralumenal Effects on Cholesterol Absorption/Synthesis

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • The primary outcomes for this study are to better understand the molecular and cellular mechanisms of cholesterol metabolism and absorption. [ Time Frame: 5 yrs ] [ Designated as safety issue: No ]

Enrollment: 35
Study Start Date: September 2005
Study Completion Date: December 2013
Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Aim 1
To assess the role of bile acid pool size changes on cholesterol absorption, synthesis and intralumenal cholesterol solubilization.
Dietary Supplement: Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic)
15 mg/kg/day for 18 days
Experimental: Aim 2
To determine whether cholesterol absorption, synthesis and solubilization will be significantly altered by changes in phospholipid content, specifically sphingolipids and phosphatidylcholine in the intestinal lumen.
Dietary Supplement: Sphingomyelin
1000mg/day for 19 days
Experimental: Aim 3
To determine the effect of Pluronic F-68 on rodent and human cholesterol absorption, synthesis and intralumenal cholesterol solubilization, fat absorption and enterocyte appearance.
Drug: Pluronic F-68
Pluronic F-68 is a "detergent" and potent inhibitor of cholesterol absorption. Dose = 0.5%-1.0% by weight of the diet.
Experimental: Aim 4
To assess intralumenal solubilization and absorption of biliary and dietary cholesterol.
Other: C13 Stable isotope of Cholesterol
Food provided for 3 days and one time dose of 113mg of C13 Cholesterol.

Detailed Description:

Cholesterol absorption plays a key role in cholesterol homeostasis and understanding the lumenal events that play key roles in absorption remain poorly understood. The aims of the present study are fourfold: 1) To determine whether previously observed effects on cholesterol absorption during bile acid feeding are related to changes in pool size and intestinal transit or meal stimulated gall bladder emptying or plasma cholecystokinin levels. 2) To determine the effect of dietary sphingomyelin on cholesterol absorption, micellar solubilization and synthesis in normal adults and to assess the effects of intralumenal cholesterol solubilization, absorption and synthesis in adults with heterozygous mdr 3 deficiency (a defect leading to low biliary phospholipid content). 3) To determine the mechanism of action of a non-ionic detergent, Pluronic F-68, by evaluating its effect on cholesterol solubilization and distribution between micelles and vesicles, on cholesterol absorption and synthesis. 4) To evaluate the intralumenal solubilization and distribution within micelles and vesicles of biliary compared to dietary cholesterol in humans and assess the impact of ezetimibe treatment on absorption of endogenous or exogenous cholesterol by assessing absorption of human contents in the biliary diverted, rat lymph fistula model. For each of these aims, subjects will be studied while consuming well-controlled diets as outpatients with a combination of human and animal techniques. Techniques employed for human studies will include state-of-the art techniques utilizing stable isotopes and isotope ratio mass spectrometry, gas chromatography. Translational studies in animals will be used including novel techniques to measure fat absorption as well as the use of the lymph fistula rat model for assessment of lipid absorption and hamsters for assessment of bile acid and sterol synthesis. Integration of animal/human techniques will provide tools to characterize the role of modifications of the intralumenal environment on cholesterol solubilization and human cholesterol absorption and synthesis.

  Eligibility

Ages Eligible for Study:   18 Years to 40 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Serum Total Cholesterol <200 mg/dl, LDL-Cholesterol <120 mg/dl
  • Apo E-3/3, Apo A IV-1/1 genotypes

Exclusion Criteria:

  • Pregnancy
  • Diabetes mellitus, other gastrointestinal, liver, kidney or heart disease
  • Allergy to soy products
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00328211

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: James E. Heubi, M.D. Children's Hospital Medical Center, Cincinnati
  More Information

Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT00328211     History of Changes
Other Study ID Numbers: DK68463, R01DK068463
Study First Received: May 18, 2006
Last Updated: December 5, 2013
Health Authority: United States: Federal Government

ClinicalTrials.gov processed this record on October 21, 2014