Cerebrovascular Reserve Measurements in Sickle Cell Disease

NCT02824406 | Unknown

• 1 other identifier: CRUISE study
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 1

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).

Conditions

Sickle Cell Disease

Keywords

Sickle Cell Anemia; Cerebrovascular Reserve; Perfusion; Vasculopathy; Magnetic Resonance Imaging

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Cerebral Metabolic Rate of Oxygen in patients and controls

  2 minutes

• Blood markers relating to anemia will be related to MRI findings

  Through study completion, an average of 1 year

• Velocity in the circle of willis assessed with 4D Flow MRI

  10 minutes

• Silent Cerebral Infarct (SCI) on T2-weighted FLAIR MRI

  10 minutes

Study Arms (2)

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

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

Interventions

Acetazolamide DRUG

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

Also known as: Diamox

Controls; Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• Sickle cell disease; either homozygous sickle cell disease (HbSS), or HbSβ0 thalassemia
• years of age or older
• Informed consent
• Similar ethnic background as Patient group
• years of age or older
• Informed consent

You may not qualify if:

• 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

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead

Study Sites (1)

Academic Medical Center

Amsterdam, Netherlands

RECRUITING

Biospecimen

Retention: SAMPLES WITHOUT DNA

The following outcomes will be assessed from veinous-drawn blood samples: Sodium, Potassium, Creatinine, Bilirubin, ASAT(SGOT), ALAT (SGPT), LDH, Ferritin, Haptoglobin, Hemoglobin, Erythrocytes, Leukocytes, Thrombocytes, MCV, MCH, MCHC, RDW, Hemoglobin, Hematocrit, Hb-F, Hb-A2, Hb-S, Hb-A2, Reticulocytes, Lymphocytes, ADAMTS13, D-Dimer, von Willebrand activity / antigen / multimer, hs-CRP, F1+2, PAI-1 antigen, t-PA-Ag antigen, NETs, Circulating histones, Metalloproteinase, Interleukin 6,13 and 18, Free HB, ADMA asymmetric dimethylarginine, VCAM, ICAM, AGEs:Pentosidine, CML - carboxyl methyl lysine, Thrombospondin, GFAP, L-selectin, VEGF, Pentraxine-3

MeSH Terms

Conditions

Anemia, Sickle Cell; Vascular Diseases

Interventions

Acetazolamide

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiadiazoles; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• AJ Nederveen

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

  PRINCIPAL INVESTIGATOR

Central Study Contacts

BJ Biemond

CONTACT

b.j.biemond@amc.uva.nl

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.

Study Record Dates

• First Submitted: February 9, 2016
• First Posted: July 6, 2016
• Study Start: August 1, 2014
• Primary Completion: June 1, 2017
• Study Completion: December 1, 2017
• Last Updated: July 6, 2016

Record last verified: 2016-07

Data Sharing

• IPD Sharing: Will share

Locations

NL (1)