HealthyNCT00328211
Intralumenal Effects on Cholesterol Absorption/Synthesis
A study testing Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic), Sphingomyelin and C13 Stable isotope of Cholesterol in people with Healthy, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy
- What is being tested?
- Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic), Sphingomyelin and C13 Stable isotope of Cholesterol
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2005to Dec 2013
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Serum Total Cholesterol <200 mg/dl, LDL-Cholesterol <120 mg/dl
- Apo E-3/3, Apo A IV-1/1 genotypes
Who cannot join
- Pregnancy
- Diabetes mellitus, other gastrointestinal, liver, kidney or heart disease
- Allergy to soy products
Trial locations and contacts
1 site in 1 country.
United States1 site
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, 45229
About this study
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.
Read the 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.
- Conditions
- Healthy
- Being tested
- Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic), Sphingomyelin, C13 Stable isotope of Cholesterol
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic)Dietary supplement
15 mg/kg/day for 18 days
SphingomyelinDietary supplement
1000mg/day for 19 days
C13 Stable isotope of CholesterolOther
Food provided for 3 days and one time dose of 113mg of C13 Cholesterol.
| Study group | Role | What they receive |
|---|---|---|
| Bile Acid | Experimental | To assess the role of bile acid pool size changes on cholesterol absorption, synthesis and intralumenal cholesterol solubilization. Receives: 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. Receives: Dietary Supplement: Sphingomyelin |
| Intralumenal | Experimental | To assess intralumenal solubilization and absorption of biliary and dietary cholesterol. Receives: Dietary Supplement: Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic); Other: C13 Stable isotope of Cholesterol |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary outcomes for this study are to better understand the molecular and cellular mechanisms of cholesterol metabolism and absorption.
Measured: 5 yrs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 May 2006 (estimated)
- Study startSep 2005
- Primary completionDec 2013
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HealthyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 35 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital Medical Center, Cincinnati
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- James E. Heubi, M.D., Principal investigator, Children's Hospital Medical Center, Cincinnati
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00328211
- Sponsor's protocol ID
- DK68463
- Other IDs
- R01DK068463
- Status last verified
- Sep 2020
- First submitted
- 18 May 2006
- Last updated
- 10 Sep 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 11907149Woollett 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.
PubMed 12611908Woollett 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.
PubMed 14988826Woollett 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.
PubMed 16407385Ramprasath 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.
PubMed 23958473
Study at a glance
From the registry record, last updated by the sponsor on 10 Sep 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Intralumenal Effects on Cholesterol Absorption/Synthesis
- ClinicalTrials.gov ID
- NCT00328211
- Acronym / sponsor ID
- DK68463
- Conditions
- Healthy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 35 participants (actual)
- Lead sponsor
- Children's Hospital Medical Center, CincinnatiUniversity, hospital or other
- Collaborators
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
- Study start
- Sep 2005
- Primary completion
- Dec 2013 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 19 May 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Bile Acid | Experimental | Dietary Supplement: Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic)To assess the role of bile acid pool size changes on cholesterol absorption, synthesis and intralumenal cholesterol solubilization. |
| Cholesterol Absorption | Experimental | Dietary Supplement: SphingomyelinTo determine whether cholesterol absorption, synthesis and solubilization will be significantly altered by changes in phospholipid content, specifically sphingolipids and phosphatidylcholine in the intestinal lumen. |
| Intralumenal | Experimental | Dietary Supplement: Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic), Other: C13 Stable isotope of CholesterolTo assess intralumenal solubilization and absorption of biliary and dietary cholesterol. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- Serum Total Cholesterol <200 mg/dl, LDL-Cholesterol <120 mg/dl
- Apo E-3/3, Apo A IV-1/1 genotypes
Key exclusion criteria (3 listed)
- Pregnancy
- Diabetes mellitus, other gastrointestinal, liver, kidney or heart disease
- Allergy to soy products
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic)15 mg/kg/day for 18 days | Dietary supplement | Bile Acid, Intralumenal |
| Sphingomyelin1000mg/day for 19 days | Dietary supplement | Cholesterol Absorption |
| C13 Stable isotope of CholesterolFood provided for 3 days and one time dose of 113mg of C13 Cholesterol. | Other | Intralumenal |
Primary outcome
The primary outcomes for this study are to better understand the molecular and cellular mechanisms of cholesterol metabolism and absorption.
Time frame: 5 yrs
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Sep 2020.
- Background: PubMed 11907149Yao 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.
- Background: PubMed 12611908Woollett 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.
- Background: PubMed 14988826Woollett 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.
- Background: PubMed 16407385Woollett 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.
- Background: PubMed 23958473Ramprasath 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
James E. Heubi, M.D. principal investigator
Children's Hospital Medical Center, Cincinnati
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Bile Acids (Cholic, Ursodeoxycholic, Chenodeoxycholic), Sphingomyelin and C13 Stable isotope of Cholesterol in people with Healthy, run by Children's Hospital Medical Center, Cincinnati at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Sep 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary outcomes for this study are to better understand the molecular and cellular mechanisms of cholesterol metabolism and absorption. (time frame: 5 yrs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00328211, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Sep 2020.