Cerebrovascular Reserve Measurements in Sickle Cell Disease

• Conditions: Sickle Cell Disease
• Interventions: Drug: Acetazolamide

• Registration Number: NCT02824406
• Lead Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

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.

Study Timeline

• Study Start: 2014-08
• Study First Submitted: 2016-02-09
• Status Verified: 2016-07
• Study First Submitted QC: 2016-07-05
• Last Update Submitted: 2016-07-05
• Study First Posted: 2016-07-06
• Last Update Posted: 2016-07-06
• Primary Completion: 2017-06
• Study Completion: 2017-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

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

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
Silent Cerebral Infarct (SCI) on T2-weighted FLAIR MRI	10 minutes	Volume of SCIs will be assessed in relation to CVR
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

Trial Locations

Locations (1)

Academic Medical Center; 🇳🇱 Amsterdam, Netherlands