Clinical trial NCT02824406: Cerebrovascular Reserve Measurements in Sickle Cell Disease
Official title: Cerebrovascular Reserve Measurements in Sickle Cell Disease: an MRI Study
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Sickle Cell Disease
Keywords: Sickle Cell Anemia
Cerebrovascular Reserve
Perfusion
Vasculopathy
Magnetic Resonance Imaging
Lead sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
Sponsor class: OTHER
First posted: 2016-07-06
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: PROBABILITY_SAMPLE
Study population: Patients are eligible if they have a diagnosis of sickle cell disease; either homozygous sickle cell disease (HbSS), or HbSβ0 thalassemia and are in a steady disease state i.e. no crisis requiring hospitalization 4 weeks prior to participation.

Brief summary: The primary aim of this study is to evaluate MRI-based cerebrovascular reserve (CVR) measurements in adult patients with Sickle Cell Disease (SCD).

The primary objective is to assess whether there is a correlation between CVR and silent cerebral infarcts (SCIs).

Detailed description: CVR is hypothesized to be impaired in SCD patients and could account for the white matter hyperintensities seen on MRI in these patients. Cerebral blood flow (CBF) alone is not sufficient to provide insight into the hemodynamic status of the brain. CVR allows us to gain insight into the capacity of the cerebrovasculature to respond to increased CBF. Vasculopathy is common in SCD and the caliber of the vessels can be assessed with 4D Flow MRI in response to actue and chronic changes in the velocity and wall shear stress on the intracranial arteries in the Circle of Willis.

This study will be performed as a single center, patient-control, cross-sectional, observational study in patients with steady-state SCD and controls. The investigators expect that patients with impaired CVR will have a greater number and/or volume of SCIs.

Eligibility criteria: Inclusion Criteria Patient group:

* Sickle cell disease; either homozygous sickle cell disease (HbSS), or HbSβ0 thalassemia
* 18 years of age or older
* Informed consent

Inclusion Criteria Control group:

* Similar ethnic background as Patient group
* 18 years of age or older
* Informed consent

Exclusion Criteria Patient group and Control group:

* 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 tumour,meningitis, overt infarct
* Brain surgery performed in the last 3 months
* Severe liver, heart or renal dysfunction (clearance \< 10 mL/min)
* Allergy to sulphonamide
* Breastfeeding
* Use of phenytoin, procaine or acetylsacylic acid ("Ascal/aspirin")
* Risk of hypokalaemia (use of diuretics, primary hyperaldosteronism)
* Addison's Disease
* Severe asthma or emphysema

Primary outcomes:
measure: Cerebrovascular Reserve (CVR) from arterial spin labelling-MRI in patients compared to controls
timeFrame: 20 minutes
Secondary outcomes:
measure: Cerebral Metabolic Rate of Oxygen in patients and controls
timeFrame: 2 minutes
measure: Blood markers relating to anemia will be related to MRI findings
timeFrame: Through study completion, an average of 1 year
measure: Velocity in the circle of willis assessed with 4D Flow MRI
timeFrame: 10 minutes
measure: Silent Cerebral Infarct (SCI) on T2-weighted FLAIR MRI
timeFrame: 10 minutes
Other outcomes:
Locations:
city: Amsterdam
country: Netherlands
facility: Academic Medical Center
Study officials:
affiliation: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
name: AJ Nederveen
role: PRINCIPAL_INVESTIGATOR
References: