The main objective of this study is to compare calcification promoting and inhibiting factors and their interactions in the serum of PXE patients and healthy controls. Secondary objectives (optional) are:1) to identify differences in cognitive…
ID
Source
Brief title
Condition
- Retina, choroid and vitreous haemorrhages and vascular disorders
- Skin and subcutaneous tissue disorders NEC
- Arteriosclerosis, stenosis, vascular insufficiency and necrosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Differences in serum levels of calcification promoting and inhibiting factors
between PXE patients and healthy controls.
Secondary outcome
1) differences in MRI brain lesions, vascular brain flow pulsatility and brain
tissue perfusion between PXE patients and healthy controls.
2) to link these differences to differences in cognitive function.
3) differences in retinal and choroidal structures and functional outcome in
PXE patients and healthy controls
4) differences in visus related QoL in PXE patients and healthy controls
Background summary
PXE is a monogenetic disease associated with calcification of the soft tissues
including the medial arterial layer. Medial arterial calcification (MAC) is
associated with increased cardiovascular risk. Recent evidence suggests an
association between PXE and cognitive disorders at a relatively young age.
Recently, inorganic pyrophosphate has been identified as an important factor in
the pathogenesis of PXE, but other circulating calcification factors also
appear to be dysregulated. How these circulating factors relate to each other
has never been studied. Therefore, this study aims to identify differences in
calcification promoting and inhibiting factors in the serum of PXE patients
compared to healthy controls. This might give more insight in the
pathophysiology of MAC in general and PXE in particular and might eventually
lead to new clues for treatment possibilities and more disease specific
treatment. Secondary aims of this study are 1) to identify differences in
cognitive disorders and MRI abnormalities in PXE patients and healthy controls
and 2) differences in retinal and choroidal structures and functional outcome
and visus related quality of life in PXE patients and healthy controls
Study objective
The main objective of this study is to compare calcification promoting and
inhibiting factors and their interactions in the serum of PXE patients and
healthy controls.
Secondary objectives (optional) are:
1) to identify differences in cognitive disorders and MRI abnormalities in PXE
patients and healthy controls
2) to identify differences in retinal and choroidal structures and functional
outcome and visus related quality of life in PXE patients and healthy
controls.
Study design
patient control study
Study burden and risks
The serum of 74 PXE patients has already been collected for the measurement of
calcification promoting and inhibiting factors for the TEMP study (METC nr
15/125; NL47602.041.15). However, a healthy control group is lacking.
Blood from additional PXE patients and healthy controls will be collected by
venepunctures. Aside from the normal risks of these venepunctures (hematoma
formation, tenderness and swelling of the puncture side, persistent bleeding
and vasovagal response) no potential health risks are assumed.
To investigate the brain involvement in PXE patients, brain MRI*s of 21 PXE
patients participating in the TEMP trial have been made at baseline. Partners
of these PXE patients will be approached to undergo brain MRI and cognitive
testing. The MRI with gadolinium yields no additional risk. We exclude patients
with renal insufficiency and therefore we do not expect the occurrence of
nephrogenic systemic fibrosis. Research participants gain no individual benefit
from their participation in this study
Heidelberglaan 100 F02.126
Utrecht 3584 CX
NL
Heidelberglaan 100 F02.126
Utrecht 3584 CX
NL
Listed location countries
Age
Inclusion criteria
For PXE patients:
1. Age 18 and older.
2. Clinical diagnosis of PXE. For the present study the revised criteria for
diagnosis of PXE from Plomp et al. (2010) will be used. At least two (or more)
criteria not belonging to the same (skin, eye, genetic) category should be
present for inclusion.
a. Skin
i. Yellowish papules and/or plaques on the lateral side of the neck and/or
flexural areas of the body
or
ii. Increase of morphologically altered elastin with fragmentation, clumping
and calcification of elastic fibers in a skin biopsy taken.
b. Eye
i. Peau d'orange of the retina; or
ii. One or more angioid streaks (AS), each at least as long as one disk
diameter. When in doubt, fluorescein or indocyanine green angiography of the
fundus is needed for confirmation.
c. Genetics
i. A pathogenic mutation of both alleles of the ABCC6gene
ii. A first-degree relative (parent, sibling or child) who meets independently
the diagnostic criteria for definitive PXE, For healthy controls:
1. Age 18 and older
Exclusion criteria
For PXE patients:
1. Subjects who are unable or unwilling to sign an informed consent., For
healthy controls:
1. Subjects who are unable or unwilling to sign an informed consent.
2. Two or more criteria for diagnosis of PXE from Plomp et al. (2010),
Additional exclusion criteria for participation in the brain MRI study:
3. Severe renal impairment (estimated creatinine clearance/eGFR of <30
ml/min/1.73m2 calculated using CKD-EPI equation).
4. A pacemaker
5. A metallic foreign body in the eye
6. Severe claustrofobia
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 | NL58514.041.16 |