Cerebrovascular Reserve Measurements in Sickle Cell Disease (CRUISE)

Cerebrovascular Reserve Measurements in Sickle Cell Disease: an MRI Study

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).

Study Overview

• Status: Unknown
• Conditions: Sickle Cell Disease
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 60

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands
    • Recruiting
    • Academic Medical Center
    • Principal Investigator: A J Nederveen, dr. ir.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Case-Control
• Time Perspectives: Cross-Sectional

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebrovascular Reserve (CVR) from arterial spin labelling-MRI in patients compared to controls	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 (%).	20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cerebral Metabolic Rate of Oxygen in patients and controls	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.	2 minutes
Blood markers relating to anemia will be related to MRI findings	Hematocrit, hemoglobin, hemolysis, red blood cell count, mean corpuscular hemoglobin concentration.	Through study completion, an average of 1 year
Velocity in the circle of willis assessed with 4D Flow MRI	Velocity (m/s) before and after acetazolamide challenge will be used to indicate cerebrovascular reserve and compared between patients and controls	10 minutes
Silent Cerebral Infarct (SCI) on T2-weighted FLAIR MRI	Volume of SCIs will be assessed in relation to CVR	10 minutes

Collaborators and Investigators

• Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Investigators: Principal Investigator: AJ Nederveen, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Study record dates

Study Major Dates

• Study Start: August 1, 2014
• Primary Completion (Anticipated): June 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: February 9, 2016
• First Submitted That Met QC Criteria: July 5, 2016
• First Posted (Estimate): July 6, 2016

Study Record Updates

• Last Update Posted (Estimate): July 6, 2016
• Last Update Submitted That Met QC Criteria: July 5, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: Magnetic Resonance Imaging; Sickle Cell Anemia; Perfusion; Cerebrovascular Reserve; Vasculopathy
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia, Sickle Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Carbonic Anhydrase Inhibitors; Natriuretic Agents; Diuretics; Anticonvulsants; Acetazolamide
• Other Study ID Numbers: CRUISE study

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes