Cerebrovascular Reserve Measurements in Sickle Cell Disease

Sickle Cell Disease Clinical Trial

— CRUISE  

Official title:

Cerebrovascular Reserve Measurements in Sickle Cell Disease: an MRI Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02824406
• Other study ID #: CRUISE study
• Status: Recruiting
• Phase: N/A
• First received: February 9, 2016
• Last updated: July 5, 2016
• Start date: August 2014
• Est. completion date: December 2017

Study information

• Verified date: July 2016
• Source: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)
• Contact: BJ Biemond
• Email: b.j.biemond[@]amc.uva.nl
• Is FDA regulated: No
• Health authority: Netherlands: Dutch Health Care InspectorateNetherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Observational

Clinical Trial 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).

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 2017
• Est. primary completion date: June 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria Patient group:

• Sickle cell disease; either homozygous sickle cell disease (HbSS), or HbSß0 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 Design

Observational Model: Case Control, Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Anemia, Sickle Cell
• Sickle Cell Disease

Intervention

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

Locations

Country	Name	City	State
Netherlands	Academic Medical Center	Amsterdam

Sponsors (1)

Lead Sponsor	Collaborator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	No
Secondary	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	No
Secondary	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	No
Secondary	Silent Cerebral Infarct (SCI) on T2-weighted FLAIR MRI	Volume of SCIs will be assessed in relation to CVR	10 minutes	No