Trial Review

The ANZCTR website will be unavailable from 1pm until 3pm (AEDT) on Wednesday the 30th of October for website maintenance. Please be sure to log out of the system in order to avoid any loss of data.

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12617001043325
Ethics application status
Approved
Date submitted
6/07/2017
Date registered
18/07/2017
Date last updated
18/07/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Cerebral arterial asymmetries in the neonate
Scientific title
Cerebral arterial asymmetries in the neonate
Secondary ID [1] 292377 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Arterial asymmetry 303940 0
Condition category
Condition code
Neurological 303294 303294 0 0
Studies of the normal brain and nervous system

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Materials
Ultrasound measurements. Transcranial Doppler ultrasonography is a non-invasive, reliable, inexpensive technique for examining neonatal parenchyma, vascular structures, and arterial hemodynamics. Transcranial cerebrovascular imaging will be performed using the portable General Electric EPIQ 9 ultrasound unit stored in the neonatal unit of the Royal Women’s Hospital, Melbourne.
Imaging software. Post-processing of the ultrasound data will be conducted using SYNAPSE (PACS) 64-bit imaging software.
Revised Edinburgh Handedness Inventory. Parental handedness will be assessed with a revised version of the Edinburgh Handedness Inventory.
Procedure
Transcranial Doppler Ultrasound Assessment. Ultrasound assessment will take place at a postnatal age of 1 to 7 days. Standard medical procedure will be followed during the analysis which will be performed by the principal investigator.
All infants will undergo 10 minutes of supine rest on a clean cot (sourced from the neonatal unit) in the ultrasound room. This room is sound proofed and will ensure that the testing environment will be without auditory or visual distractions.
Parents will accompany their infant into the ultrasound room and will be instructed to have fed the infant prior to the scanning session. Parents will be situated at the head of the cot, behind the principal investigator so as not to distract the infant. Infant behavioural state will be recorded. If an infant becomes distressed, an attempt will be made to soothe the infant using methods that the parent would normally use.
Prior to the hemodynamic analysis, an initial two-dimensional B mode Grey-Scale Imaging screening will be performed through the anterior fontanelle in the sagittal plane for lenticulostriate artery identification. The lenticulostriate arteries will then be screened for the presence of any pathology.
An C3-10, 6 MHz curvilinear probe with an insonation angle close to 0° will be used. Further settings will include a small sample volume of 1 mm with a low velocity wall filter of 4cm-s to reduce noise. Two lenticulostriate arties in each cerebral hemisphere will be chosen for further scanning based on the clarity of the image and orientation of the vessel (i.e. the two arteries on each side that are most oriented in the vertical plane). Once the arteries are identified, B-Flow Imaging will be activated and the probe will be moved so at to optimise the visualisation of one of the selected vessels. This mode uses non-Doppler technology to display true hemodynamics and enables direct visualization of the vessel without the limitations of Doppler. These images are clear and unaffected by gain. Dual-view Imaging will then be initiated to replicate the image into two identical left and right images. The left image will be activated and flow measurements will be performed on the longitudinal sections of the selected artery, prior to its first bifurcation, with Pulsed Wave Doppler Mode. Peak systolic velocity (PSV), end-diastolic velocity (EDV), and heart rate measures will be obtained from homogeneous blood flow wave patterns over five consecutive cardiac cycles. Three diameter measures will be taken in the exact location of the artery in the corresponding right B-Flow image. The procedure will then be repeated for the second unilateral and two contralateral lenticulostriate arteries in a randomized order.

Using a transtemporal approach, the transducer will be placed on the left temporal bone, below the zygomatic arch, to locate the proximal portion of the middle cerebral artery (horizontal segment that lies between the circle of Willis and branches of the lenticulostriate arteries). An initial two-dimensional B mode Grey-Scale Imaging screening will be performed through the temporal window for the identification and screening of the left middle cerebral artery. Using the same probe, ultrasound settings, and imaging protocol, B-Flow and Pulsed Wave Doppler will be utilised in dual-view imaging to record arterial diameter and peak systolic velocity (PSV), end-diastolic velocity (EDV), and heart rate measures of the proximal portion of the middle cerebral artery.
The distal portion of the middle cerebral artery (distal to the origins of the lenticulostriate arteries) approximately 10 mm from the middle cerebral artery bifurcation/trifurcation will be located and haemodynamic and diameter measures will be repeated on the left and right side in a randomized order. At this distance the vessel will have a uniform diameter and will require minimal angle correction. In any necessary instance, an angle of correction will be performed if the angle of incidence is greater than 15° to ensure the transducer remains parallel to the vector of blood flow and accurate measures are obtained.
Proximal haemodynamic measures reflect the general haemodynamic status of the basal ganglia, posterior limb of the internal capsule and insular and lateral surfaces of the cortex. Distal measures reflect neocortical flow. Differences between proximal and distal measures will be calculated offline to determine subcortical flow.
All images will be stored on optical disc for off-line analysis using SYNAPSE (PACS) 64-bit imaging software and will be averaged across the waveforms for each infant.
Infant Head Posture Assessment. The naturalistic observation of infant head posture will occur after the transcranial Doppler ultrasound analysis. This ensures that haemodynamic analyses are conducted blind to participant laterality. While lying in the cot, the infant’s head will be held gently in a midline position and maintained in this position until no lateralised pressure is experienced against the examiner’s hands. The head will then be released. Once the infant’s head posture deviates from the midline, a five minute period of observation will begin. During this period, the head posture together with the infant’s ongoing behavioural state will be recorded on a check sheet in consecutive 30 second intervals. This five minute observation period will be filmed with a GoPro Hero4 recording device (out of the line of sight of the infant) so as to eliminate any subjective bias in scoring. Reliability of head posture scores will be assessed with a third party during data analysis.
Each data collection session, including the arterial scan, neonatal head posture assessment, and assessment of parental handedness, will take 30 to 45 minutes.
Intervention code [1] 298556 0
Not applicable
Comparator / control treatment
No control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 302680 0
Left-right differences in structure and flow of middle cerebral arteries are measured
Timepoint [1] 302680 0
At time of scan
Primary outcome [2] 302681 0
Left-right differences in the structure and flow of lenticulostriate arteries are measured
Timepoint [2] 302681 0
At time of scan
Secondary outcome [1] 336741 0
Parental handedness assessed with Revised Edinburgh Handedness Inventory
Timepoint [1] 336741 0
Immediately after scan
Secondary outcome [2] 336742 0
Neonatal head posture is assessed
Timepoint [2] 336742 0
Immediately after scan

Eligibility
Key inclusion criteria
The study population will include 100 healthy term neonates (age 1 to 7 days old), born via normal vaginal delivery or caesarean section at the Royal Women’s Hospital from March 2017 to December 2017 (10 month period). All newborns born between 36 and 42 weeks of completed gestation with an Apgar score of more than seven at five minutes (AS5min > 7) will be eligible for enrolment. Parental handedness will also be recorded.
Minimum age
12 Hours
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Neonatal Exclusion criteria. Infants will be excluded if born to mothers with significant complications during pregnancy or delivery. Criteria of an uncomplicated delivery are the absence of resuscitation received after delivery and admission to the neonatal intensive and special care nursery. Infants will also be excluded if they have significant neonatal conditions including intracranial pathology, congenital malformations, metabolic or genetic disease, central nervous system infection, congenital heart disease, and neonatal abstinence syndrome.
Maternal exclusion criteria. Women younger than 18 years and older than 42 years will be excluded from the study. Further exclusion criteria for women include diagnoses of autoimmune disorders, pre gestational diabetes mellitus, gestational diabetes, cardiac disease, drug/s and substance use (current use if addicting drugs or current therapy related to their addiction), instances of suspected/detected foetal abnormality, chronic/persistent hypertension (>140/90), infections (including active genital herpes, syphilis, HIV +), Pre-eclampsia, as well as diagnoses of neurological and mental health conditions. Participants who are not competent in English will be excluded from the study to ensure effective communication and understanding between the parent, principal investigator and associate investigators throughout the study.

Study design
Purpose
Natural history
Duration
Cross-sectional
Selection
Defined population
Timing
Prospective
Statistical methods / analysis
Many neonatal flow studies do not directly assess side-to-side arterial asymmetries and either assess flow unilaterally or report a left-right mean. Studies that do assess side-to-side cerebral flow typically average the flow values across the sample and therefore do not determine left or right flow dominance on an individual basis.
A small effect size is typical in the adult and neonatal literature. A representative effect size calculated from the available neonatal studies, where left-right middle cerebral artery flow velocity differences are reported and sufficient information to calculate an effect size is given, is 0.29. At an alpha level of 0.05, a power analysis indicates that a total sample of 100 participants would generate statistical power at the .89 level, assuming a repeated-designs t-test.
The data will be analysed using IBM SPSS Statistics (version 22) software. Intercorrelations between the laterality variables (i.e. head turning (HP score) and parental handedness (LQ score)) will be examined and the feasibility of extracting a single laterality factor will be explored.
One-tailed paired t-tests will compare the differences between the left and right paired arterial parameters of the population as a whole. This will also be conducted for the laterality groups, as classified by the neonatal head turning. If the assumptions of the t-test are not upheld, a non-parametric Wilcoxon signed-rank test will be run instead. Sample specific descriptive statistics of age, race, sex, and laterality will also be included.
Intercorrelations between the laterality variables (i.e. head turning (HP score) and parental handedness (LQ score)) will be examined and the feasibility of extracting a single laterality factor will be explored. Otherwise, there will be a need for separate analyses. The analyses will be conducted for the subcortical and neocortical middle cerebral artery measures, and lenticulostriate arteries. Tests of normality and homoscedasticity (namely Levene’s test of equality of variance and Box’s test of equality of covariance matrices) will be run on each dataset.
On the assumption that there will be two well differentiated left-right laterality groups in the sample, a discriminant function analysis (DFA) will be used to assess the contribution of arterial parameters to group membership. Failing this, simple linear multiple regression analyses will be conducted to evaluate how well the hemodynamic measures predict degree of handedness — as determined by their HP score. The influence of parental handedness on behavioural laterality and on arterial asymmetry will also be examined.
The independent variables of this analysis will be the hemodynamic predictors and the dependent variables will be the laterality groups. Prior to analysis, the predictor variables will be inspected to ensure that the assumptions for the analysis are upheld. Frequency tables and box-and-whisker plots will be created in order to better understand the distribution of the data.
Lateral group membership will be predicted with the following parameters: diameter, VSYS, VDIA, volume flow rate, and sex. The percentage of correct classification of the cases by the discriminant equation will be analysed.
Cohen‘s rule of thumb for effect size interpretations will be used for between-group comparisons: r = .10 (small effect), r = .30 (medium effect), and r = .50 (large effect). The significance of the all analyses will be determined with a 95% confidence level at p < .05.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
1/03/2017
Date of last participant enrolment
Anticipated
30/11/2017
Actual
Date of last data collection
Anticipated
30/11/2017
Actual
Sample size
Target
100
Accrual to date
51
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 8495 0
The Royal Women's Hospital - Parkville
Recruitment hospital [2] 8496 0
Frances Perry House - Parkville
Recruitment postcode(s) [1] 16582 0
3052 - Parkville

Funding & Sponsors
Funding source category [1] 296932 0
University
Name [1] 296932 0
University of Melbourne
Country [1] 296932 0
Australia
Primary sponsor type
Individual
Name
Prof Michael Saling
Address
12th floor Redmond Barry Building,
University of Melbourne
Melbourne School of Psychological Sciences
Parkville Campus, Melbourne VIC 3010
Country
Australia
Secondary sponsor category [1] 295938 0
None
Name [1] 295938 0
Address [1] 295938 0
Country [1] 295938 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298137 0
Royal Womens Hospital HREC
Ethics committee address [1] 298137 0
Ethics committee country [1] 298137 0
Australia
Date submitted for ethics approval [1] 298137 0
06/05/2016
Approval date [1] 298137 0
04/07/2016
Ethics approval number [1] 298137 0
16/18
Ethics committee name [2] 298139 0
Frances Perry House Medical Advisory Committee
Ethics committee address [2] 298139 0
Ethics committee country [2] 298139 0
Australia
Date submitted for ethics approval [2] 298139 0
21/09/2016
Approval date [2] 298139 0
23/11/2016
Ethics approval number [2] 298139 0
2016-17

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 76122 0
Ms Anica Jansen van Vuuren
Address 76122 0
12th floor Redmond Barry Building,
University of Melbourne
Melbourne School of Psychological Sciences
Parkville Campus, Melbourne VIC 3010
Country 76122 0
Australia
Phone 76122 0
+61401791952
Fax 76122 0
Email 76122 0
[email protected]
Contact person for public queries
Name 76123 0
Anica Jansen van Vuuren
Address 76123 0
12th floor Redmond Barry Building,
University of Melbourne
Melbourne School of Psychological Sciences
Parkville Campus, Melbourne VIC 3010
Country 76123 0
Australia
Phone 76123 0
+61041791952
Fax 76123 0
Email 76123 0
[email protected]
Contact person for scientific queries
Name 76124 0
Anica Jansen van Vuuren
Address 76124 0
12th floor Redmond Barry Building,
University of Melbourne
Melbourne School of Psychological Sciences
Parkville Campus, Melbourne VIC 3010
Country 76124 0
Australia
Phone 76124 0
+61401791952
Fax 76124 0
Email 76124 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.