Cerebral Blood Flow and Childhood Obstructive Sleep Apnea

NCT ID: NCT02995837

Last Updated: 2024-07-09

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 47 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2016-10-31
• Study Completion Date: 2022-01-01

Brief Summary

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.

Detailed Description

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.

Conditions

Obstructive Sleep Apnea Syndrome

Study Design

• Observational Model Type: CASE_CONTROL
• Study Time Perspective: PROSPECTIVE

Study Groups

Obstructive Sleep Apnea Syndrome (OSAS)

The study duration is estimated at 12-14 months approximately. However, this will depend on the timing of treatment as they will undergo testing pre- and post-OSAS treatment. Participation will entail a total of 8 visits including:

Pre-treatment - neurocognitive testing, and CBF during wakefulness testing duration is one full day. The CBF nighttime testing is one full night.

Post-treatment - Six to twelve weeks after clinically indicated surgical treatment, OSAS participants will have a repeat baseline polysomnogram (one full night) to assess for residual OSA. Six and twelve months after the surgical treatment, the sleep study with the nighttime CBF testing, as well as the daytime neurocognitive testing and CBF testing will be repeated to assess for changes.

Sleep Study

Intervention Type: 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.

Neurocognitive Testing

Intervention Type: OTHER

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

CBF During Wakefulness

Intervention Type: 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.

CBF During Sleep

Intervention Type: 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.

Controls

The study will include 7 total visits for controls: a baseline sleep study to ensure normalcy, three full days of neurocognitive testing and CBF testing (baseline, 6 and 12 months), and three sleep studies with CBF testing (baseline, 6 and 12 months). A daytime visit and one night time visit may be scheduled during a 24-hour period if the participant and family wish so. Otherwise, they will be scheduled on separate days.

Sleep Study

Intervention Type: 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.

Neurocognitive Testing

Intervention Type: OTHER

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

CBF During Wakefulness

Intervention Type: 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.

CBF During Sleep

Intervention Type: 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.

Interventions

Sleep Study

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.

Intervention Type: OTHER

Neurocognitive Testing

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

Intervention Type: OTHER

CBF During Wakefulness

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.

Intervention Type: OTHER

CBF During Sleep

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.

Intervention Type: OTHER

Other Intervention Names

Polysomnography; Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Daytime/Wakefulness); Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Nighttime/Sleep)

Eligibility Criteria

Inclusion Criteria

1. 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.

2. Absence of neurologic, cardiovascular, pulmonary, or any other chronic illness with the exception of well-controlled asthma

3. No prior surgery on the nose, palate or oropharynx including an adenotonsillectomy

4. No current drug intake that may interfere with testing such as sedatives or stimulants

5. No prior treatment of sleep-disordered breathing

6. 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.

7. Parental/guardian permission (informed consent) and if appropriate, child assent.

1. 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.

2. Absence of neurologic, cardiovascular, pulmonary, or any other chronic illness with the exception of well-controlled asthma

3. No prior surgery on the nose, palate or oropharynx including an adenotonsillectomy

4. No current drug intake that may interfere with testing such as sedatives or stimulants

5. No prior treatment of sleep-disordered breathing

6. Polysomnographic recording criteria: Normal control subjects must have an AHI ≤ 1.5/hour.

7. Parental/guardian permission (informed consent) and if appropriate, child assent.

Exclusion Criteria

1. Previous adenotonsillectomy

2. Previous use of CPAP

3. Craniofacial anomalies that can interfere with upper airway anatomy (e.g., Treacher-Collins syndrome)

4. Genetic syndromes (e.g., Trisomy 21, Prader-Willi)

5. Attention deficit hyperactivity disorder (ADHD) on medication

6. Developmental delay

7. Non-English speaking participants due to the nature of neurobehavioral testing

1. Previous adenotonsillectomy

2. Previous use of CPAP

3. Craniofacial anomalies that can interfere with upper airway anatomy (e.g., Treacher-Collins syndrome)

4. Genetic syndromes (e.g., Trisomy 21, Prader-Willi)

5. ADHD on medication

6. Developmental delay

7. Positive Pediatric Sleep Questionnaire

8. Non-English speaking participants due to the nature of neurobehavioral testing

• Minimum Eligible Age: 6 Years
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Children's Hospital of Philadelphia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ignacio E. Tapia, MD, MS

Role: PRINCIPAL_INVESTIGATOR

Children's Hospital of Philadelphia

Locations

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

K01HL130719

Identifier Type: NIH

Identifier Source: secondary_id

View Link

16-012750

Identifier Type: -

Identifier Source: org_study_id