CBF and Childhood OSAS

Obstructive Sleep Apnea Syndrome Clinical Trial

Official title:

Cerebral Blood Flow and Neurocognition in Children With Obstructive Sleep Apnea

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02995837
• Other study ID #: 16-012750
• Secondary ID: K01HL130719
• Status: Completed
• Start date: September 2016
• Est. completion date: January 1, 2022

Study information

• Verified date: February 2024
• Source: Children's Hospital of Philadelphia
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: January 1, 2022
• Est. primary completion date: January 1, 2022
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 12 Years

Eligibility

Inclusion Criteria (OSAS subjects):

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. Exclusion Criteria (OSAS Subjects)

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 Inclusion Criteria (Control subjects)

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 (Control Subjects)

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

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea Syndrome
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

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

Locations

Country	Name	City	State
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania

Sponsors (2)

Lead Sponsor	Collaborator
Children's Hospital of Philadelphia	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Determine the association between CBF regulation and severity of OSAS		Up to 12 months
Other	Determine the association between cognitive and behavioral measurements and severity of OSAS		Up to 12 months
Primary	Difference in cerebral blood flow (CBF) at baseline between OSAS and controls	To determine whether children with OSAS have impaired blood flow regulation elicited by hypercapneic challenge compared to normal controls.	Up to 24 hours
Secondary	Comparison of the change in CBF from baseline to study completion between OSAS and control subjects	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.	Up to 12 Months