The current study aims to evaluate magnetic resonance imaging (MRI)-based CVR measurements with ACZ in SCD. It*s primary objective is to assess whether there is a correlation between CVR with silent cerebral infarcts (SCI) (i.e. the cerebrovascular…
ID
Source
Brief title
Condition
- Haemolyses and related conditions
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
cerebral blood flow (CBF) measured by ASL; velocity in the MCA measured by 3D
TOF MRA; volume and count of semi-automatically delineated cerebral vessels on
3D TOF MRA; volume and count of SCI on 3D fluid attenuated inverse recovery
(FLAIR) and T2-weighted MRI scans; wall shear stress measurements
Secondary outcome
count and volume of SCI on previous scans, if available; hematological whole
blood parameters including Hb, reticulocytes, free Hb, HbF, Hct, leukocytes,
neutraphil count, platelet count, creatinine, total/direct bilirubine, LDH,
ferritine; hematological inflammatory parameters including hsCRP, pentraxine-3,
AGEs (pentosidine and N*-(carboxy-methyl) lysine, CML), ADMA, von Willebrand
factor antigen, sP-selectine, sE-selectine, VCAM-1, ICAM-1, VEGF and
nucleosomes; heartbeat frequency; complication frequency.
Background summary
Impairment of the cerebrovascular reserve (CVR) is a suggested cause for
cerebrovascular pathology in sickle cell disease (SCD). It can be evaluated by
vasodilatation induction by acetazolamide (ACZ), which has previously shown
good results. However, previous imaging modalities did not supply a direct
quantification of CVR parameters. Newer imaging modalities, such as arterial
spin labeling (ASL), 3-dimensional time-of-flight magnetic resonance
angiography (3D TOF MRA) and 3D-flow allow a more concise quantification of CVR
parameters. Furthermore, they allow evaluating their time course during
vasodilatation induction. These modalities may clarify the pathophysiological
process leading from disturbed autoregulation to cerebrovascular pathology in
SCD.
Study objective
The current study aims to evaluate magnetic resonance imaging (MRI)-based CVR
measurements with ACZ in SCD. It*s primary objective is to assess whether there
is a correlation between CVR with silent cerebral infarcts (SCI) (i.e. the
cerebrovascular biomarker). The secondary objectives are to investigate whether
1) CVR are correlated with clinical or vascular biomarkers; 2) 3D TOF MRA in
cooperation with ASL can display compensatory collateral circulation in SCD and
3) whole brain averaged vessel diameter is more sensitive than velocity
measurement in the medial cerebral artery (MCA). Patients will be compared with
healthy controls to estimate the level of disease severity in relation to the
heatlhy population.
Study design
The current study will be a single center observational cross-sectional cohort
study with intervention and with maximal duration of four years. It consists of
one single MRI-examination consisting of four parts of 15 minutes: 1)
anatomical imaging; 2) functional imaging before vasodilatation induction; 3)
functional imaging during vasodilatation induction; 4) functional imaging after
vasodilatation induction. In order to study the CVR, 16 mg/kg ACZ (Diamox®),
with a maximum of 1400 mg, will be administrated to induce vasodilatation.
Study burden and risks
MRI is harmless, the ACZ injection has been declared safe and venapunction is
routine in patients with SCD.
Parameters obtained by blood drawn in this study will be used clinically as
well. Presumably, participation is associated with minimal burden and risks.
As cranial MRI is not routinely performed in adults with SCD, coincidental
findings are potentially beneficial. The studied population represents the
group of patients with the highest disease severity, and is, thus,
representable.
Meibergdreef 9
Amsterdam, NL 1105 AZ
NL
Meibergdreef 9
Amsterdam, NL 1105 AZ
NL
Listed location countries
Age
Inclusion criteria
- sickle cell disease (HbSS or HbS0)
- 18 years of age or older
- informed consent
Exclusion criteria
* inability of the patient to provide informed consent or legally incompetent/incapacitated to do so
* contraindications for MRI, such as pregnancy, claustrophobia or the presence of metal in the body
* sickle cell crisis at the moment of participation
* history of cerebral pathology that compromises measurements, such as cerebral palsy, brain tumor, meningitis, overt infarct
* brain surgery performed in the last 3 months
* severe liver, heart or renal dysfunction (clearance < 10 mL/min)
* allergy to sulfonamide
* breastfeeding
* use of phenytoin, procain, acetylsacylic acid (*Ascal/aspirine*)
* risk of hypokalemia (use of diuretics, primary hyperaldosteronism)
* Addison*s Disease
* severe asthma or emphysema
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 | NL37995.018.11 |