To study *in vivo* lipid and apolipoprotein metabolism in patients with FH4, and to compare the results with healthy family controls and dyslipidemic patients with mutations in established lipid genes(i.e. FH1 * FH3). This will ultimately help to…
ID
Source
Brief title
Condition
- Lipid metabolism disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Tracer/tracee ratio, pool size, fractional catabolic rate, and production rate
in FH4 subjects compared with (family) controls and/or dyslipidemic patients
with mutations in established lipid genes.
Secondary outcome
n.v.t.
Background summary
Familial hypercholesterolemia (FH) is characterized by increased low density
lipoprotein (LDL) cholesterol and increased cardiovascular risk. There are 3
known genes (LDLR, ApoB, PCSK9) in which mutations can lead to the FH phenotype
(FH1 to 3 respectively). However, in approximately 5-10% of patients such a
mutation cannot be found, despite family-based linkage studies (the so called
FH4 group). Therefore, a more elaborate approach is deemed necessary, where
data derived from transcriptome, proteome, and metabolome studies are combined
to find novel genes and metabolic pathways in lipid metabolism. We aim to
acquire in depth phenotyping in selected FH4 patients by extensive lipoprotein
kinetic flux studies yielding insights into the pathophysiological mechanism of
FH4.
Study objective
To study *in vivo* lipid and apolipoprotein metabolism in patients with FH4,
and to compare the results with healthy family controls and dyslipidemic
patients with mutations in established lipid genes(i.e. FH1 * FH3). This will
ultimately help to answer the fundamental question as to whether FH4 is a
result of overproduction or a decreased catabolism of ApoB containing
lipoproteins.
Study design
Matched case-control study
Intervention
n.v.t.
Study burden and risks
Participants will visit the AMC for 1 or 2 full day(s) (7.30 am till 6.00 pm).
Metabolic fluxes will be measured with stable isotope tracers that behave like
their natural substrates and are therefore not harmful. At 21 timepoints blood
samples will be collected, in total 279 ml. In the week prior to the admission
participiants will be asked to keep track of their daily diet. On the day after
the study day a last blood sample will be collected at the patients home at
8.00 am.
Patiënts with FH4 will be asked to participate in 2 study days, 1 after a 4
week wash-out period of lipid lowering therapy.
We state that the scientific insight of our findings will outweigh the minimal
burdens and risks in this study.
Meibergdreef 9
Amsterdam-Zuidoost 1105AZ
NL
Meibergdreef 9
Amsterdam-Zuidoost 1105AZ
NL
Listed location countries
Age
Inclusion criteria
- Diagnosis of familial hypercholesterolemia of unknown origin (FH4) based on Dutch Lipid Clinic Network criteria (Nordestgaard et al. 2013) and negative DNA-testing (mutations in LDLR, ApoB, PCSK9).
- Untreated LDL-cholesterol levels of > 95th percentile for affected members
- 18-65 years of age;Controls:
- Unaffected family member with untreated LDL-cholesterol between 20-60th percentile
- 18-65 years of age
Or:
- Persons with mutations in LDLR, APOB, or PCSK9 gene or other genes involved in lipid metabolism.
- 18-65 years of age
Exclusion criteria
· Heavy alcohol use
· Dysthyroidism
· Pregnancy, breastfeeding
· Renal insufficiency (creatinine >150 µmol/L)
· Diabetes mellitus
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL61012.018.17 |
| OMON | NL-OMON26254 |