We would like to study whether aberrant heparansulfate synthesis in HME subjects leads to impaired glucose metabolism, dyslipidemia and subsequent increased cardiovascular risk as well as impaired adrenal gland function when compared to unaffected…
ID
Source
Brief title
Condition
- Metabolic and nutritional disorders congenital
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Changes in glucose metabolism (oral glucose tolerance tests) in subjects with
HME with either EXT1 or EXT2 mutation compared to unaffected control subjects.
Secondary outcome
Changes in cardiovascular risk (lipidprofile and ECG changes) in subjects with
HME with either EXT1 or EXT2 mutation compared to unaffected control subjects.
Changes in adrenal gland function (synacthen test) in subjects with HME with
either EXT1 or EXT2 mutation compared to unaffected control subjects.
Background summary
EXT-1 or EXT-2 genes are of pivotal importance in normal organ and skeleton
development due to their role in heparansulfate synthesis, a sugar chain
present in all human cells .Hereditary multiple exostoses (HME) is a clinical
syndrome comprising lifelong risk of development of cartilage/bone tumor
formation and therefore are regularly checked at the OLVG orthopaedic
outpatient clinic . Previous research from our group has shown that HME
subjects are characterized by impaired insulin secretion, a hormone involved in
glucose metabolism. Moreover, we found that mice with EXT1 or EXT2
heterozygous mutations (eg murine model of human HME) are characterized by
dyslipidemie/fasting hypertriglyceridemi due to impaired cholesteroluptake in
the liver. Moreover, we gathered evidence that heparansulfates are implicated
in normal adrenal function, a gland that synthesizes cortisol. In order to
investigate whether these findings hold true for HME subjects with either EXT1
or EXT2 mutations or unaffected familiy member, we would like to execute this
study.
Study objective
We would like to study whether aberrant heparansulfate synthesis in HME
subjects leads to impaired glucose metabolism, dyslipidemia and subsequent
increased cardiovascular risk as well as impaired adrenal gland function when
compared to unaffected family members.
Study design
observational study with functional (oral glucose tolerance test and synacthen)
tests
Study burden and risks
Despite a minimal risk of short term hypotension upon synacthen bolus infusion,
no sideeffects are expected. Moreover, we believe that the outcome of these
three studyquestions regarding glucose tolerance, cardiovascular risk and
adrenal gland function categorized to EXT1 or EXT2 genotype renders usefull l
information for phenoptype and clincal stastus of subjects with HME. Moreover,
we think that these results provide pathophysiological information about
glucose tolerance, cardiovascular risk and adrenal gland function in the
general population. Therefore we think that the benefits of this study
outhweight the minimal conveyed risk.
Meibergdreef 9, kamer F4-159.2 1105 AZ Amsterdam
1105 AZ Amsterdam
NL
Meibergdreef 9, kamer F4-159.2 1105 AZ Amsterdam
1105 AZ Amsterdam
NL
Listed location countries
Age
Inclusion criteria
*Age between 18 and 70 years
*Clinical diagnosis of Hereditary Multipele Exostoses (HME) with/without proven EXT1/EXT2 mutation (patient) OR unaffected family member (control)
*Written informed consent
Exclusion criteria
* History of psychiatric disease (psychosis)
* Pregnancy or female participants at childbearing age not using adequate anticonception (due to synacthen infusion)
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 | NL38725.018.12 |
| Other | NTR 10510 |