Objective Neurocognitive Assessment of Young Children With Sickle Cell Disease by Eye-Tracking

NCT07721155 | Completed DMC

• 2 other identifiers: NL82004.018.222022.0539
• Study Type: observational
• Target: 93
• Locations: 1 country
• Sites: 1

Brief Summary

Evidence indicates that Sickle Cell Disease (SCD) threatens neurodevelopmental outcome. Although children with SCD may be heterogeneously affected, neurocognitive impairment may already be present in toddlers. Neurocognitive functioning is an important determinant of adaptive daily life functioning later in life and is influenced by both the course of the disease and the often suboptimal environment in which afflicted children grow up. Early identification of children at the highest risk of neurocognitive impairment would enable the deployment of early interventions to mitigate the detrimental effects of SCD on the developing brain. In order to develop such interventions, a deeper understanding of the underlying pathophysiological mechanisms is required. Therefore the main aim is to study early neurocognitive functioning and development in children with SCD between the ages of 6 and 24 months old.

Conditions

Sickle Cell Disease; Sickle Cell; Neurocognition, Child

Keywords

sickle cell; cognition

Outcome Measures

Primary Outcomes (10)

• Processing speed in the gap condition (Gap/Overlap task)

  The speed of responding to a novel peripheral stimulus when the central stimulus disappears before the peripheral target appears. Measured as reaction time (RT) via eye-tracking in infants with sickle cell disease (SCD). Unit of Measure: Milliseconds (ms)

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Processing accuracy in the gap condition (Gap/Overlap task)

  The precision of responding to a novel peripheral stimulus when the central stimulus disappears before the peripheral target appears. Measured as a binomial outcome (accurate/inaccurate) per trial via eye-tracking in infants with SCD. Unit of Measure: Proportion of accurate trials

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Orienting attention speed in the overlap condition (Gap/Overlap task)

  The speed of orienting attention away from a central stimulus toward a peripheral target when the central stimulus remains on screen. Measured as RT in the overlap condition expressed as percentage change relative to mean RT in the gap condition, via eye-tracking in infants with SCD. Unit of Measure: Percentage (%)

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Orienting attention accuracy in the overlap condition (Gap/Overlap task)

  The precision of orienting attention toward a peripheral target when the central stimulus remains on screen. Measured as a binomial outcome (accurate/inaccurate) per trial via eye-tracking in infants with SCD. Unit of Measure: Proportion of accurate trials

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Alerting attention without external cues (Gap/Overlap task)

  The ability to maintain focus on the task without external attention-grabbing cues. Measured as a binomial outcome per trial (completed without attention grabber: yes/no) via eye-tracking in infants with SCD. Unit of Measure: Proportion of trials completed without attention grabber

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Sustained attention across trials (Gap/Overlap task)

  The ability to attend to the task over a longer period. Measured as the number of trials completed expressed as a percentage of the total possible trials, via eye-tracking in infants with SCD. Unit of Measure: Percentage (%)

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Fixation duration during free viewing (Freeview task)

  The amount of time the eyes remain stably focused on a specific location, defined as periods of stable gaze between successive saccades. Measured as mean fixation duration via eye-tracking in infants with SCD. Unit of Measure: Milliseconds (ms)

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Habituation (Habituation task)

  The process of becoming accustomed to a repeatedly presented stimulus. Measured as the number of trials required to reach the pre-defined habituation criterion via eye-tracking in infants with SCD. Unit of Measure: Number of trials

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Recognition (Habituation task)

  The ability to distinguish a previously presented stimulus from a novel one. Measured as the absolute difference in looking time toward the habituation stimulus versus the novel stimulus, via eye-tracking in infants with SCD. Unit of Measure: Percentage (%)

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

• Novelty preference (Habituation task)

  The tendency to inspect a novel stimulus relative to a previously presented one. Measured as looking time toward the novel stimulus as a percentage of total looking time, via eye-tracking in infants with SCD. Unit of Measure: Percentage (%)

  T1 (age 6 months), T2 (age 12 months), T3 (age 18 months), T4 (age 24 months)

Secondary Outcomes (4)

• Demographic and perinatal characteristics assessed via parent-reported questionnaire

  At study visit of 6, 12 18 or 24 months of age, depending on the enrollment age. The first visit in the study

• Behavioral and emotional functioning assessed using the Strengths and Difficulties Questionnaire (SDQ)

  study visit at 24 months of age

• Development assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III)

  study visit at 24 months of age

• Plasma proteomic biomarker profile assessed via blood sample in children with SCD

  study visit at 12 months of age and study visit at 24 months of age

Study Arms (2)

Patient group

Infants between 6 and 24 months of age diagnosed with sickle cell disease

Other: eyetracking; Diagnostic Test: blood work; Other: Strengths and difficulties questionnaire (SDQ); Other: TNO AZL Preschool Children Quality of Life (TAPQOL); Other: Bayley Scale of Infant Development III (BSID)

Healthy subject group

Infants between 6 and 24 months of age without sickle cell disease

Other: eyetracking; Other: Strengths and difficulties questionnaire (SDQ); Other: TNO AZL Preschool Children Quality of Life (TAPQOL); Other: Bayley Scale of Infant Development III (BSID)

Interventions

eyetracking OTHER

Eye-tracking is an objective, non-invasive method and particularly suited to assess neurodevelopmental outcome in infants.

Healthy subject group; Patient group

blood work DIAGNOSTIC_TEST

proteomics analyses methylation analyses

Patient group

Strengths and difficulties questionnaire (SDQ) OTHER

The strengths and difficulties questionnaire is a conventional instrument used to measure the presence of psychosocial problems, the child's strengths and the influence of psychosocial problems on daily functioning.

Healthy subject group; Patient group

Bayley Scale of Infant Development III (BSID) OTHER

The Bayley Scale of Infant Development is a conventional instrument used to measure developmental outcome in infants

Healthy subject group; Patient group

TNO AZL Preschool Children Quality of Life (TAPQOL) OTHER

The TNO-AZL Preschool Children Quality of Life is a questionnaire that measures the health-related quality of life of children over the last three months

Healthy subject group; Patient group

Eligibility Criteria

• Age: 6 Months - 24 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Probability Sample

Study Population

Children between the 6 and 24 months are invited to participate in the study.

You may qualify if:

• Age 6 - 24 months old
• Inhabitant of the Netherlands
• Written informed consent from parent/caretaker.

You may not qualify if:

• Refused informed consent from parents/care-taker
• Diagnosis of visual impairment (which cannot be corrected by glasses)
• Diagnosis of a (co-morbid) congenital developmental condition
• Any neurological condition, unrelated to SCD, that could affect the central nervous system, such as brain trauma, epilepsy and meningitis/encephalitis.

Sponsors & Collaborators

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

Study Sites (1)

Amsterdam UMC

Amsterdam, 1105AZ, Netherlands

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Retention: blood sample Description: proteomics and methylation analyses will be done prospectively

MeSH Terms

Conditions

Anemia, Sickle Cell

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

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: prof. dr.

Study Record Dates

• First Submitted: June 22, 2026
• First Posted: July 22, 2026
• Study Start: March 16, 2023
• Primary Completion: November 27, 2025
• Study Completion: December 2, 2025
• Last Updated: July 22, 2026

Record last verified: 2026-06

Locations

NL (1)