CRUISE: Cerebrovascular Reserve Measurements in Sickle Cell Disease

Sponsor

Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) (Other)

Overall Status

Unknown status

CT.gov ID

NCT02824406

Collaborator

(none)

Enrollment

Location

Duration (Months)

1.5

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Sickle Cell Disease	Drug: Acetazolamide

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.

Study Design

Study Type:

Observational

Anticipated Enrollment :

60 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Cerebrovascular Reserve Measurements in Sickle Cell Disease: an MRI Study

Study Start Date :

Aug 1, 2014

Anticipated Primary Completion Date :

Jun 1, 2017

Anticipated Study Completion Date :

Dec 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Patients CVR assessment consists of CBF measurement with arterial spin labelling (ASL)-MRI before and after intravenous administration of 16mg/kg acetazolamide (Diamox)	Drug: Acetazolamide Acetazolamide is administered to all participants to induce vasodilation, in order to assess the physiologic response on cerebral blood flow. Other Names: Diamox
Controls CVR assessment consists of CBF measurement with arterial spin labelling (ASL)-MRI before and after intravenous administration of 16mg/kg acetazolamide (Diamox)	Drug: Acetazolamide Acetazolamide is administered to all participants to induce vasodilation, in order to assess the physiologic response on cerebral blood flow. Other Names: Diamox

Arm

Intervention/Treatment

Patients

CVR assessment consists of CBF measurement with arterial spin labelling (ASL)-MRI before and after intravenous administration of 16mg/kg acetazolamide (Diamox)

Drug: Acetazolamide

Acetazolamide is administered to all participants to induce vasodilation, in order to assess the physiologic response on cerebral blood flow.

Other Names:

Diamox

Controls

CVR assessment consists of CBF measurement with arterial spin labelling (ASL)-MRI before and after intravenous administration of 16mg/kg acetazolamide (Diamox)

Drug: Acetazolamide

Acetazolamide is administered to all participants to induce vasodilation, in order to assess the physiologic response on cerebral blood flow.

Other Names:

Diamox

Outcome Measures

Primary Outcome Measures

Cerebrovascular Reserve (CVR) from arterial spin labelling-MRI in patients compared to controls [20 minutes]
Cerebral blood flow (CBF mL/100g/min) measurement before, during, and after, an intravenous administration of 16mg/kg acetazolamide. The percentage change in CBF will be used as a measure for CVR (%).

Secondary Outcome Measures

Cerebral Metabolic Rate of Oxygen in patients and controls [2 minutes]
Oxygen extraction fraction and cerebral blood flow are proportional to the cerebral metabolic rate of oxygen. Using the CBF from the primary outcome, and having measured the T2 of blood (which is dependent on oxygen), we can derive the oxygen extraction fraction, which allows us to calculate the cerebral metabolic rate of oxygen (CMRO2) and compare patients with controls.
Blood markers relating to anemia will be related to MRI findings [Through study completion, an average of 1 year]
Hematocrit, hemoglobin, hemolysis, red blood cell count, mean corpuscular hemoglobin concentration.
Velocity in the circle of willis assessed with 4D Flow MRI [10 minutes]
Velocity (m/s) before and after acetazolamide challenge will be used to indicate cerebrovascular reserve and compared between patients and controls
Silent Cerebral Infarct (SCI) on T2-weighted FLAIR MRI [10 minutes]
Volume of SCIs will be assessed in relation to CVR

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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