Intralumenal Effects on Cholesterol Absorption/Synthesis
| Status: | Completed |
|---|---|
| Conditions: | Healthy Studies |
| Therapuetic Areas: | Other |
| Healthy: | No |
| Age Range: | 18 - 40 |
| Updated: | 4/21/2016 |
| Start Date: | September 2005 |
| End Date: | December 2013 |
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.
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.
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.
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.
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
We found this trial at
1
site
3333 Burnet Avenue # Mlc3008
Cincinnati, Ohio 45229
Cincinnati, Ohio 45229
1-513-636-4200
Cincinnati Children's Hospital Medical Center Patients and families from across the region and around the...
Click here to add this to my saved trials
