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Completed

NCT Number: NCT02995837

Cerebral Blood Flow and Childhood Obstructive Sleep Apnea

Obstructive sleep apnea syndrome (OSAS) causes hypoxemia and hypercapnia, which may impair cerebral blood flow and cause deficits in behavior. This is a case-control study designed to investigate cerebral blood flow and neurocognitive function in children with OSAS when compared to these findings from normal children. The study hypothesis is that children with OSAS have an impaired cerebral blood flow during wakefulness and sleep compared to normal controls, and that the degree of this impairment correlates with neurocognitive function.

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Key information

Conditions

Obstructive Sleep Apnea Syndrome Apnea Dyssomnias Nervous System Diseases Respiration Disorders Respiratory Tract Diseases Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

6 year–12 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

About this study

OSAS is characterized by repetitive occlusion of the upper airway during sleep that results in hypoxemia, hypercapnia and arousal from sleep. Children with the obstructive sleep apnea syndrome (OSAS) have impaired behavior and cognition compared to normal controls. Previous studies in adults with OSAS have shown significant alterations of cerebral blood flow during wakefulness and sleep and our preliminary data showed blunted cerebral blood flow response to hypercapnia in children with OSAS during wakefulness. However, it is unknown whether children with OSAS also have impaired cerebral blood flow during sleep. It is also unknown whether the deficits in behavior and cognition in children are associated with cerebral blood flow dysregulation.

This study will investigate whether the changes in cerebral blood flow during wakefulness and sleep elicited by hypercapneic challenge, differ in children with OSAS compared to normal controls. Additionally the study will evaluate the changes in cerebral blood flow during wakefulness and sleep elicited by hypercapneic challenge in children with OSAS before and after treatment (adenotonsillectomy, adenoidectomy, or tonsillectomy). Finally, the study will investigate whether the changes in cerebral blood flow elicited by the aforementioned testing correlate with neurocognitive outcomes.

Children with OSAS aged 6-12 years will be recruited following a clinical polysomnogram. Normal age- and gender-matched controls will be recruited from the general community.

The primary interventions of this study for the two groups (OSAS and controls) are: sleep studies, neurocognitive testing, measurement of cerebral blood flow by near-infrared spectroscopy during hypercapnic challenges conducted during wakefulness and sleep. In addition, OSAS subjects will be re-tested after clinical treatment of OSAS to evaluate for resolution of OSAS, and all subjects will be re-tested at two separate time points after baseline to compare changes due to the treatment of OSAS versus those occurring secondary to normal development.

Who can participate

Healthy volunteers accepted: Yes

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

Inclusion criteria

(OSAS subjects):

  • Age between 6 years and 12 years. The lower limit criterion was selected to include children who can understand and cooperate with testing. The upper limit criterion was selected to avoid overlap with the adult presentation of OSAS.
  • Absence of neurologic, cardiovascular, pulmonary, or any other chronic illness with the exception of well-controlled asthma
  • No prior surgery on the nose, palate or oropharynx including an adenotonsillectomy
  • No current drug intake that may interfere with testing such as sedatives or stimulants
  • No prior treatment of sleep-disordered breathing
  • Polysomnographic recording criteria: subjects with OSAS must have an obstructive apnea hypopnea index (AHI) ≥ 5/hour and be a candidate for clinically-indicated surgical treatment.
  • Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion criteria

(OSAS Subjects)

  • Previous adenotonsillectomy
  • Previous use of CPAP
  • Craniofacial anomalies that can interfere with upper airway anatomy (e.g., Treacher-Collins syndrome)
  • Genetic syndromes (e.g., Trisomy 21, Prader-Willi)
  • Attention deficit hyperactivity disorder (ADHD) on medication
  • Developmental delay
  • Non-English speaking participants due to the nature of neurobehavioral testing

Inclusion criteria

(Control subjects)

  • Age between 6 years and 12 years. The lower limit criterion was selected to include children who can understand and cooperate with testing. The upper limit criterion was selected to avoid overlap with the adult presentation of OSAS.
  • Absence of neurologic, cardiovascular, pulmonary, or any other chronic illness with the exception of well-controlled asthma
  • No prior surgery on the nose, palate or oropharynx including an adenotonsillectomy
  • No current drug intake that may interfere with testing such as sedatives or stimulants
  • No prior treatment of sleep-disordered breathing
  • Polysomnographic recording criteria: Normal control subjects must have an AHI ≤ 1.5/hour.
  • Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion criteria

(Control Subjects)

  • Previous adenotonsillectomy
  • Previous use of CPAP
  • Craniofacial anomalies that can interfere with upper airway anatomy (e.g., Treacher-Collins syndrome)
  • Genetic syndromes (e.g., Trisomy 21, Prader-Willi)
  • ADHD on medication
  • Developmental delay
  • Positive Pediatric Sleep Questionnaire
  • Non-English speaking participants due to the nature of neurobehavioral testing

Treatment and study plan

Sleep Study

Other

Overnight, video-recorded sleep study will be performed in a dedicated pediatric sleep lab. Sleep architecture, apneas and hypopneas, arterial oxygen saturation and end-tidal carbon dioxide tension will be evaluated during the sleep study. Safety measures including arterial oxygen saturation using pulse oximetry, EEG and EKG will be continuously monitored during the study.

Other names: Polysomnography

Neurocognitive Testing

Other

Cognitive and behavioral measures including intelligence, attention, working memory, and processing speed will be assessed by a trained psychologist.

CBF During Wakefulness

Other

Cerebral blood flow (CBF) will be measure using Diffuse optical and correlation spectroscopy (DOS/DCS), a non-significant risk device used to collect data for this study but not being tested as part of the protocol. Light sources and detectors which are embedded in a rubber pad will be attached to the subject's head in order to record right and left hemispheric cerebral blood flow, total hemoglobin concentration and tissue oxygen saturation. Measurements will be continuously recorded during the study and averaged for purposes of statistical analysis. With DOS/DCS in place, ventilatory response to hypercapnia will be determined using the rebreathing technique, a standard clinical test. While CBF is being measured, subjects will wear nose clips and sit comfortably breathing through a mouthpiece while the level of carbon dioxide is adjusted over a 3-4 minute period. Oxygen and carbon dioxide levels will be carefully monitored throughout the testing.

Other names: Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Daytime/Wakefulness)

CBF During Sleep

Other

This is the same as the CBF testing during wakefulness/daytime except that it will be done during a sleep study performed with a continuous positive airway pressure (CPAP) mask not nose clips and a mouthpiece. With DOS/DCS in place, ventilatory response to hypercapnia will be determined using the rebreathing technique. While CBF is being measured, OSAS subjects will receive an individualized positive pressure aimed at treating obstructive sleep apnea and controls will receive a standard pressure. End-tidal carbon dioxide will be measured via a port in the mask. A constant flow of carbon dioxide will be introduced to the circuit, a slowly adjusted until the patient arouses or for a maximum of 3 minutes, whichever occurs first. One trial will be attempted in each sleep stage (slow-wave sleep and rapid-eye-movement) with a minimum of 15 minute of breathing room air between challenges. Oxygen and carbon dioxide levels will be carefully monitored throughout the testing.

Other names: Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Nighttime/Sleep)

Primary outcomes

  1. Change in Cerebral Blood Flow (CBF) at Baseline Between Obstructive Sleep Apnea Syndrome (OSAS) and Controls

    Time frame: Baseline measurements, up to 24 hours

    To determine whether children with OSAS have impaired blood flow regulation elicited by hypercapneic challenge compared to normal controls at baseline.

Secondary outcomes

  1. Comparison of the Change in CBF From Baseline to Study Completion Between OSAS and Control Subjects

    Time frame: Up to 12 Months

    Only children who completed 2 or more repeated measurements were included in the analysis. The change in CBF measurements obtained at baseline when compared at 6 and 12 months after baseline for controls and after adenotonsillectomy for OSAS subjects. The slope of the change in CBF over time is reported: Delta CBF/Delta time, units= percentage over year. Minimum values are -100, maximum values +100, positive values mean better outcome.Cerebral blood flow were measured non-invasively while the child was breathing oxygen mixed with carbon dioxide.

Other outcomes

  1. Association Between CBF Regulation and Severity of OSAS

    Time frame: Up to 12 months

    Children who completed baseline measurements were included. Correlation coefficients between the obstructive apnea hypopnea index and relative change of cerebral blood flow in children with obstructive sleep apnea and Controls are reported.

    The Correlation Coefficient is calculated by dividing the Covariance of the apnea hypopnea index and CBF by the Standard deviation of the apnea hypopnea index and CBF. Units of the standard deviation of CBF= unit of CBF. So, in the correlation coefficient formula, units get canceled. The correlation coefficient does not have any units and can be positive or negative. In this case positive correlation coefficients signal better regulation of CBF.

  2. Behavior Rating Inventory of Executive Function Global Executive Functioning T-score

    Time frame: baseline

    Children who completed baseline measurements were included. One child in the obstructive sleep apnea arm did not complete the Behavior Rating Inventory of Executive Function testing.

    Behavior Rating Inventory of Executive Function (global executive functioning T score) is reported between the 2 groups. Because this measures uses a T score, a score of 50 is considered average for the population. The scale is 0-100, with higher scores signaling executive functioning impairment. T-scores of 60-64 are in the mildly elevated range, and scores equal to or exceeding 65 are considered to be significantly elevated. The typical standard deviation (SD) observed is 10.

Sponsors and collaborators

Lead sponsor

Children's Hospital of Philadelphia

Other

Collaborators

  • National Heart, Lung, and Blood Institute (NHLBI)

Registry information

Official study title

Cerebral Blood Flow and Neurocognition in Children With Obstructive Sleep Apnea

Important dates

Study start
2016
Primary completion
2022
Study completion
2022
First posted
Dec 16, 2016
Registry last updated
Jul 9, 2024

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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