Intralumenal Effects on Cholesterol Absorption/Synthesis

NCT00328211 | Completed DMC

• 2 other identifiers: DK68463R01DK068463
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Outcome Measures

Primary Outcomes (1)

• The primary outcomes for this study are to better understand the molecular and cellular mechanisms of cholesterol metabolism and absorption.

  5 yrs

Study Arms (3)

Bile Acid

EXPERIMENTAL

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)

Cholesterol Absorption

EXPERIMENTAL

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

Intralumenal

EXPERIMENTAL

To assess intralumenal solubilization and absorption of biliary and dietary cholesterol.

Dietary Supplement: Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic); Other: C13 Stable isotope of Cholesterol

Interventions

Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic) DIETARY_SUPPLEMENT

15 mg/kg/day for 18 days

Bile Acid; Intralumenal

Sphingomyelin DIETARY_SUPPLEMENT

1000mg/day for 19 days

Cholesterol Absorption

C13 Stable isotope of Cholesterol OTHER

Food provided for 3 days and one time dose of 113mg of C13 Cholesterol.

Intralumenal

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

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

You may not qualify if:

• Pregnancy
• Diabetes mellitus, other gastrointestinal, liver, kidney or heart disease
• Allergy to soy products

Sponsors & Collaborators

• Children's Hospital Medical Center, Cincinnati: lead
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK): collaborator

Study Sites (1)

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, 45229, United States

Location

Related Publications (5)

• Yao L, Heubi JE, Buckley DD, Fierra H, Setchell KD, Granholm NA, Tso P, Hui DY, Woollett LA. Separation of micelles and vesicles within lumenal aspirates from healthy humans: solubilization of cholesterol after a meal. J Lipid Res. 2002 Apr;43(4):654-60.

  PMID: 11907149 BACKGROUND

• Woollett LA, Buckley DD, Yao L, Jones PJ, Granholm NA, Tolley EA, Heubi JE. Effect of ursodeoxycholic acid on cholesterol absorption and metabolism in humans. J Lipid Res. 2003 May;44(5):935-42. doi: 10.1194/jlr.M200478-JLR200. Epub 2003 Mar 1.

  PMID: 12611908 BACKGROUND

• Woollett LA, Buckley DD, Yao L, Jones PJ, Granholm NA, Tolley EA, Tso P, Heubi JE. Cholic acid supplementation enhances cholesterol absorption in humans. Gastroenterology. 2004 Mar;126(3):724-31. doi: 10.1053/j.gastro.2003.11.058.

  PMID: 14988826 BACKGROUND

• Woollett LA, Wang Y, Buckley DD, Yao L, Chin S, Granholm N, Jones PJ, Setchell KD, Tso P, Heubi JE. Micellar solubilisation of cholesterol is essential for absorption in humans. Gut. 2006 Feb;55(2):197-204. doi: 10.1136/gut.2005.069906.

  PMID: 16407385 BACKGROUND

• Ramprasath VR, Jones PJ, Buckley DD, Woollett LA, Heubi JE. Effect of dietary sphingomyelin on absorption and fractional synthetic rate of cholesterol and serum lipid profile in humans. Lipids Health Dis. 2013 Aug 19;12:125. doi: 10.1186/1476-511X-12-125.

  PMID: 23958473 BACKGROUND

MeSH Terms

Interventions

Bile Acids and Salts; Sphingomyelins

Intervention Hierarchy (Ancestors)

Steroids; Fused-Ring Compounds; Polycyclic Compounds; Neutral Glycosphingolipids; Glycosphingolipids; Glycolipids; Glycoconjugates; Carbohydrates; Lipids; Phospholipids; Membrane Lipids; Sphingolipids

Study Officials

• James E. Heubi, M.D.

  Children's Hospital Medical Center, Cincinnati

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 18, 2006
• First Posted: May 19, 2006
• Study Start: September 1, 2005
• Primary Completion: December 1, 2013
• Study Completion: December 1, 2013
• Last Updated: September 10, 2020

Record last verified: 2020-09

Locations

US (1)