- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01574417
Plant Stanols and Gene Expression Profile
The Effects of Plant Stanol Esters on Intestinal Mucosal Gene Expression Profiles and Microbiota Composition in Healthy Human Subjects
Plant sterols and stanols are dietary components that are naturally present in plants. Their biological function in plants is comparable with these of cholesterol in animals. They are structurally related to cholesterol, but are absorbed by enterocytes to a much lesser extent. It is generally accepted that they inhibit intestinal cholesterol absorption and consequently lower serum low-density lipoprotein (LDL) cholesterol concentrations up to 10% at daily intakes of 2.5 g. The exact underlying mechanism of the plant sterol/stanol mediated reduction in intestinal cholesterol absorption is still unknown. It has been suggested that they lower the activity of sterol uptake transporters like Niemann-Pick C1 like 1 protein (NPC1L1) in enterocytes, otherwise several studies indicated that these compounds could activate the liver X receptor (LXR) in enterocytes, thereby activating the ABC transporters involved in the intestinal cholesterol metabolism, whereas recently suggestions have been made that plant sterols and stanols activate transintestinal cholesterol excretion (TICE). This is the direct cholesterol secretion from the blood into the intestinal lumen, in which the enterocytes play a central role. None of these assumptions have so far been evaluated in humans.
Objective: The major objective of the present study is to examine the acute effects of dietary plant stanol esters on the intestinal mucosal gene expression profiles in intestinal biopsies in healthy volunteers. The minor objective is to investigate whether semi-long-term use (3 weeks) of plant stanol esters have an effect on microbiota composition.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
lant sterols and stanols are dietary components that are naturally present in plants. Their biological function in plants is comparable with these of cholesterol in animals. They are structurally related to cholesterol, but are absorbed by enterocytes to a much lesser extent. It is generally accepted that they inhibit intestinal cholesterol absorption and consequently lower serum low-density lipoprotein (LDL) cholesterol concentrations up to 10% at daily intakes of 2.5 g. The exact underlying mechanism of the plant sterol/stanol mediated reduction in intestinal cholesterol absorption is still unknown. It has been suggested that they lower the activity of sterol uptake transporters like Niemann-Pick C1 like 1 protein (NPC1L1) in enterocytes, otherwise several studies indicated that these compounds could activate the liver X receptor (LXR) in enterocytes, thereby activating the ABC transporters involved in the intestinal cholesterol metabolism, whereas recently suggestions have been made that plant sterols and stanols activate transintestinal cholesterol excretion (TICE). This is the direct cholesterol secretion from the blood into the intestinal lumen, in which the enterocytes play a central role. None of these assumptions have so far been evaluated in humans.
Objective: The major objective of the present study is to examine the acute effects of dietary plant stanol esters on the intestinal mucosal gene expression profiles in intestinal biopsies in healthy volunteers. The minor objective is to investigate whether semi-long-term use (3 weeks) of plant stanol esters have an effect on microbiota composition.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Limburg
-
Maastricht, Limburg, Netherlands
- Maastricht University Medical Centre
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Aged between 18-60 years
- BMI between 20-30kg/m2
- mean serum total cholesterol < 7.8mmol/L
Exclusion Criteria:
- unstable body weight
- active cardiovascular diseases
- gastrointestinal diseases
- use of cholesterol-lowering drugs
- use of lipid-lowering therapy
- abuse of drug or alcohol
- pregnant or breast-feeding women
- current smoker
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Plant stanol-enriched margarine
|
Subjects will undergo a postprandial test for 5.5 hours, in which 26.7gram of the plant stanol-enriched margarine is consumed together with a high-fat milkshake. Daily consumption of 20 gram of a plant stanol-enriched margarine (providing daily 3.0 gram of plant stanols), for a period of 3 weeks. |
Placebo Comparator: control margarine
|
Subjects will undergo a postprandial test for 5.5 hours, in which 26.7gram of the control margarine is consumed together with a high-fat milkshake. Daily consumption of 20 gram of a control margarine (providing daily 3.0 gram of plant stanols), for a period of 3 weeks. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
intestinal mucosal gene expression profiles
Time Frame: Measured at day 8 and day 64. Changes will be calculated between day 8 and day 64.
|
Measured at day 8 and day 64. Changes will be calculated between day 8 and day 64.
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
microbiota composition
Time Frame: measured after 3 weeks consumption of controle margarine and the plant stanol-enriched margarine. Changes will be calculated between these 2 interventions.
|
measured after 3 weeks consumption of controle margarine and the plant stanol-enriched margarine. Changes will be calculated between these 2 interventions.
|
lipoprotein profile
Time Frame: measured at baseline and after 3 weeks
|
measured at baseline and after 3 weeks
|
plasma glucose concentration
Time Frame: measured at day 8 and day 64, on 8 time points
|
measured at day 8 and day 64, on 8 time points
|
plasma plant stanol concentration
Time Frame: measured at baseline and after 3 weeks
|
measured at baseline and after 3 weeks
|
Collaborators and Investigators
Collaborators
Investigators
- Principal Investigator: Jogchum Plat, Dr, Maastricht University Medical Centre
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- METC 12-3-005
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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