What is the difference in fractional cholesterol absorption, measured by means of the dual isotope method, between mildly hypercholesterolemic subjects with high plasma campesterol levels compared to subjects with low plasma campesterol levels?
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The difference in fractional cholesterol absorption, as measured by means of
the dual isotope method, between subjects with high and low plasma campesterol
levels respectively.
Secondary outcome
not applicable
Background summary
Intestinal cholesterol absorption varies considerably in the general
population, ranging between 20-70%. Previous studies have suggested a
classification of subjects with high or low cholesterol absorption. In most
studies, levels of non-cholesterol sterols have been used as markers for
cholesterol absorption and synthesis respectively. Based on these markers, a
classification of subjects with high or low cholesterol absorption, the
so-called high and low absorbers, has been suggested. The high absorbers are
thought to have elevated cholesterol levels due to high absorption, whereas the
low absorbers have elevated levels based on high synthesis. Subsequently, it
has been suggested that high absorbers do not or hardly benefit from statin
treatment alone, either with respect to cholesterol reduction and the
recurrence of CHD. Therefore, the high absorbers may benefit from the addition
of cholesterol absorption inhibitors.
This underscores the need to identify high absorbers in order to treat them
accurately. Therefore, easy accessible markers are essential in clinical
practice. However, whether high and low absorbers indeed can be identified
based on plasma levels of non-choelsterol sterols has never been verified by
means of actual cholesterol absorption measurement. Besides the fact that the
validity of these markers may be questionable, they also do not provide any
indication regarding the quantity of cholesterol that is absorbed.
In the current study we will measure actual cholesterol absorption rates in
mildly hypercholesterolemic subjects, who have been identified as high and low
cholesterol absorbers, based on their plasma plant sterol levels (campesterol
levels). For this purpose, we have measured plant sterol concentrations in a
relatively large population of 160 individuals (Dahlia-1 study). In the present
study, cholesterol absorption will be measured in the 6 subjects with the
highest and the 6 subjects with the lowest campesterol concentrations
respectively. This will enable us to investigate whether plasma plant sterols
can be used as a marker of cholesterol absorption. If this is indeed the case,
in a series of future studies, we will evaluate whether high and low absorbers
also differ in other aspects of cholesterol metabolism and whether they respond
differently to cholesterol lowering therapies.
Study objective
What is the difference in fractional cholesterol absorption, measured by means
of the dual isotope method, between mildly hypercholesterolemic subjects with
high plasma campesterol levels compared to subjects with low plasma campesterol
levels?
Study design
This is a cross-sectional study, which comprises a single cholesterol
absorption measurement by means of the dual isotope method. First, subjects
will attend a screening visit, consisting of a medical history, physical
examination and blood sampling to determine lipid profile. At the second study
visit the actual cholesterol absorption measurement will start, consisting of a
bloodsample with an ensuing single intravenuous administration of 13C
cholesterol and an oral administration of 2H7 cholesterol via a standardized
breakfast. Subjects will return to their homes and will attend the AMC in the
subsequent three mornings for additional blood sampling. Percent of intestinal
cholesterol absorption will be calculated by dividing the plasma ratio of 13C
and 2H7 enrichment by the ratio of 13C and 2H7 cholesterol species administered
to the subjects.
Study burden and risks
Hardly any risks are involved in this study. At screening, a single blood
sample will be obtained. At the second visit, an intravenous catheter will be
inserted, followed by four blood drawings, during the following three days.
This may lead to a hematoma at the site of venepuncture. Furthermore, two
kinds of cholesterol markers will be administered to the study subjects, both
orally and intravenously. These so-called stable isotopes are not harmful, as
they behave as their natural substrates. Finally, we do not expect any
unfavorable effects of discontinuation of any possible cholesterol lowering
medication, neither from a possible 8-week cessation of fish oil or fibrates.
Meibergdreef 9
1015 AZ Amsterdam
Nederland
Meibergdreef 9
1015 AZ Amsterdam
Nederland
Listed location countries
Age
Inclusion criteria
Healthy male and female subjects, aged 18-65 years old, with an LDL-cholesterol concentration between 3.0 and 5.0 mmol/l, who participated in the Dahlia-1 study and belong to the 6 subjects with the highest or to the 6 subjects with the lowest plasma campesterol levels respectively. One subject with the subsequently highest campesterol levels will be asked to undergo a cholesterolabsorption measurement as well, in order for us to test the quantification of cholesterol isotopes by our laboratory.
Exclusion criteria
Excluded are persons with a genetic hyperlipoproteinemia like familial hypercholesterolemia, LPL-deficiency, familial dysbeta lipoproteinemia and familial hypertriglyceridemia. Also people with diabetes mellitus, severe hypertriglyceridemia, uncontrolled hypertension or history of arterial disease including unstable angina, myocardial infarction, recent transient ischaemic attacks or a cerebro-vascular accident, will be excluded.
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL25657.018.08 |