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Completed

NCT Number: NCT07721155

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

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.

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Key information

Conditions

Sickle Cell Disease Anemia Anemia, Hemolytic Anemia, Hemolytic, Congenital Anemia, Sickle Cell Congenital, Hereditary, and Neonatal Diseases and Abnormalities Genetic Diseases, Inborn Hematologic Diseases Hemic and Lymphatic Diseases Hemoglobinopathies Neurocognition, Child Sickle Cell

Age range

6 month–24 month

Sex eligibility

All sexes

Study type

Observational

Primary location

Amsterdam UMC

Amsterdam, 1105AZ, Netherlands

About this study

Objective: The main aim is to study early neurocognitive functioning and development in very young children with SCD. The secondary aims are to 1) (i) identify demographic, psychosocial and clinical determinants and (ii) identify biomarkers associated with early neurocognitive deficits in young children with SCD. 2) Analyze the association between early neurocognitive functioning and adaptive daily life functioning.

Study design: Prospective observational study with an accelerated longitudinal design. The accelerated longitudinal design allows for the inclusion of children from a broad age range (6 - 24 months). During the total study period of 30 months, children can enroll in the study at the ages of 6, 12, 18 and 24 months. After enrollment, children will visit every 6 months until they reach the age of 24 months. This design spans the age range of interest in a shorter period of time and a smaller load on participants as compared to a conventional longitudinal design.

Methods: Eye-tracking measurements will take place at every study visit. Demographic, psychosocial and clinical characteristics of the SCD group will be collected using prospective and structured clinical registration as part of regular clinical care. Demographic, psychosocial and clinical information of the control group will be collected using a parent questionnaire administered during the first and last study visit. Blood samples of children with SCD will be taken as part of regular blood checks at the age of 12 and/or 24 months (depending on the age of enrollment in the study). The Child Behavior Checklist, TNO AZL Preschool Children Quality of Life and the Bayley Scale of Infant and Child Development will be administered to all children at the age of 24 months.

Main study parameters/endpoints: Neurocognitive functioning, as measured using eye-tracking.

Secondary study parameters/ endpoints: The following determinants will be measured: Demographic, psychosocial and clinical characteristics, as measured as part of regular clinical care (SCD group) or via parent questionnaire (control group) and Biomarkers, as measured in blood (SCD group). Adaptive daily life functioning, as measured by quality of life, behavioural and emotional functioning questionnaire, and general (cognitive) development assessment.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

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

Exclusion criteria

  • 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.

Treatment and study plan

eyetracking

Other

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

blood work

Diagnostic Test

proteomics analyses methylation analyses

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.

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

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

Primary outcomes

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

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

    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)

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

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

    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

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

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

    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 (%)

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

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

    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

  5. Alerting attention without external cues (Gap/Overlap task)

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

    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

  6. Sustained attention across trials (Gap/Overlap task)

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

    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 (%)

  7. Fixation duration during free viewing (Freeview task)

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

    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)

  8. Habituation (Habituation task)

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

    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

  9. Recognition (Habituation task)

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

    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 (%)

  10. Novelty preference (Habituation task)

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

    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 (%)

Secondary outcomes

  1. Demographic and perinatal characteristics assessed via parent-reported questionnaire

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

    Demographic and perinatal information collected via a structured parent/caretaker questionnaire, including child age, sex, ethnicity, country of origin, parental education level (as proxy for socioeconomic status), and perinatal information (e.g. breastfeeding, birth characteristics). Clinical characteristics (e.g. SCD genotype, disease severity, treatment) are extracted from electronic health records.

    Unit of Measure: Categorical and continuous variables (reported descriptively)

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

    Time frame: study visit at 24 months of age

    Parent-reported behavioral and emotional functioning measured using the SDQ, a validated screening instrument. The SDQ assesses five domains: emotional symptoms, conduct problems, hyperactivity/inattention, peer relationship problems, and prosocial behavior. Scores are reported per subscale and as a total difficulties score.

    Unit of Measure: Scale score (0-40 total difficulties score)

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

    Time frame: study visit at 24 months of age

    Standardized assessment of development administered by a trained examiner at age 24 months using the BSID-III (Cognitive and Motor Scale). Scores are reported as scaled scores with a normative mean of 10 (SD=3). Unit of Measure: Scaled score

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

    Time frame: study visit at 12 months of age and study visit at 24 months of age

    A blood sample is collected from children with SCD to identify plasma proteomic biomarkers related to disease severity and neurological functioning. Samples are analyzed using unbiased proteomics analyses to characterize protein expression profiles.

    Unit of Measure: Protein expression levels (reported as relative abundance)

Sponsors and collaborators

Lead sponsor

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

Other

Registry information

Acronym: ONSET

Important dates

Study start
2023
Primary completion
2025
Study completion
2025
First posted
Jul 22, 2026
Registry last updated
Jul 22, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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