Arterial Function Parameters and Transcranial Doppler Velocity in Paediatric Patients With Sickle Cell Disease

Study Overview
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Brief Summary
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Structural and functional changes in arteries are increasingly being recognized as significant features of sickle cell disease. This study aims to determine whether there are differences in arterial function parameters between children with sickle cell disease with normal and abnormal transcranial Doppler velocity. After informed consent is obtained, participants will have vascular, Transcranial Doppler, haematological and biochemical parameters measured. Researchers will compare children with sickle cell disease who have normal Transcranial Doppler velocity and no history of stroke with children with those who have an abnormal Transcranial Doppler velocity with or without a history of stroke to see if there are significant differences in arterial function parameters.

Detailed Description
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Structural and functional changes in arteries are increasingly being recognized as significant features of sickle cell disease and arterial function in sickle cell anaemia (SCA) is gaining importance. The goal of this observational study is to compare arterial parameters in children with sickle cell disease who have normal or abnormal Transcranial Doppler velocity. The main question it aims to answer is: whether there is a significant difference in arterial Function parameters measured by aortic pulse wave velocity, augmentation index, brachial and central blood pressure in Jamaican children with Sickle Cell anaemia who attend the Sickle Cell Unit in Kingston Jamaica who are reported to have normal or an abnormal Transcranial Doppler velocity and whether the probability of having an abnormal Transcranial Doppler velocity or higher arterial function parameters is increased by specific biophysical markers. Participants who are identified will be informed about the study and potential risks. All patients giving written informed consent will then undergo arterial function (arteriograph,TensioMed® Arteriograph24™,Budapest, H-1181 Hungary), Transcranial Doppler, haematological and biochemical measurements. Researchers will compare children with sickle cell disease who have normal Transcranial Doppler velocity and no history of stroke with children with this illness who have an abnormal Transcranial Doppler velocity to see if there are significant differences in regional arterial function.

Official Title
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The Relationship of Transcranial Doppler Velocity With Other Vascular Measurements in Children With Sickle Cell Anaemia

Conditions
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Sickle Cell Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pediatric participants with sickle cell anaemia (HbSS, HbSβ0 thalassemia, HbSD, HbSOArab) Age: Between 4-16 years of age, at the time of enrolment Has had at least one complete TCD study whether or not on hydroxyurea treatment or in a clinical trial. Parent or guardian willing and able to provide informed consent and child gives assent Ability to comply with study-related evaluations. Exclusion Criteria: Participants who meet any of the following criteria are disqualified from enrollment in the study: Patients in whom a TCD study cannot be completed Patients who have had an Erythrocyte transfusion in the past two months Patients who are acutely ill or have had an acute infection in the past two weeks

Ages Eligible for Study
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Minimum Age: 4 Years
Maximum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Paediatric patients with sickle cell disease with normal TCD velocity without clinical stroke<br>Patients in this group will be aged 4 to 16 years with sickle cell anaemia with no prior history of stroke or previous Transcranial Doppler study showing a maximum time-averaged mean velocity of greater than 169 cm/sec, and who have not received a red cell transfusion in the past two months and are considered to be at steady state. | |
| Paediatric patients with sickle cell disease with an abnormal TCD velocity (with or without stroke)<br>Patients in this group will be aged 4 to 16 years with sickle cell anaemia with an abnormal TCD velocity, who have not received a red cell transfusion in the past two months and are considered to be at steady state. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean difference in aortic pulse wave velocity in mmHg between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke | The primary outcome of aortic pulse wave velocity in mmHg, will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes at the study visit. | 
| Mean difference in aortic augmentation index, in % between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke. | The primary outcome of aortic augmentation index, in % will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes at the study visit. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean difference in brachial augmentation index, in %, between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke | Brachial augmentation index, in %, will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes at the study visit. | 
| Mean difference in aortic systolic blood pressure in mmHg between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke | Aortic systolic blood pressure in mmHg, will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes at the study visit. | 
| Mean difference in aortic pulse pressure, in mmHg between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke | Aortic pulse pressure in mmHg, will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes at the study visit. | 
| Mean difference in brachial systolic pressure in mmHg, between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke | Brachial systolic pressure in mmHg will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes at the study visit. | 
| Mean difference in brachial diastolic pressure in mmHg between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke. | Brachial diastolic pressure in mmHg will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes | 
| Difference in mean arterial pressure in mmHg between patients with an abnormal transcranial Doppler Velocity compared to those with a normal Transcranial Doppler velocity without stroke | Mean arterial pressure in mmHg will be measured in all patients with an Arteriograph 24 (TensioMed, Budapest, Hungary). Before the assessment, the patient will be allowed to rest for 5 -10 minutes. An appropriate cuff size will be used for each patient. The test will be carried out in a calm, temperature-controlled room. | Three measurements will be taken over 10 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sickle Cell disease, Transcranial Doppler Velocity, Arterial Stiffness, Augmentation Index, Arterial Function