Cerebral Blood Flow and Childhood Obstructive Sleep Apnea

NCT02995837 | Completed Results DMC

• 2 other identifiers: 16-012750K01HL130719
• Study Type: observational
• Target: 47
• Locations: 1 country
• Sites: 1

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.

Conditions

Obstructive Sleep Apnea Syndrome

Keywords

Obstructive Sleep Apnea Syndrome; Cerebral Blood Flow; Neurocognition

Outcome Measures

Primary Outcomes (1)

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

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

  Baseline measurements, up to 24 hours

Secondary Outcomes (1)

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

  Up to 12 Months

Other Outcomes (2)

• Association Between CBF Regulation and Severity of OSAS

  Up to 12 months

• Behavior Rating Inventory of Executive Function Global Executive Functioning T-score

  baseline

Study Arms (2)

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.

Other: Sleep Study; Other: Neurocognitive Testing; Other: CBF During Wakefulness; Other: CBF During Sleep

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.

Other: Sleep Study; Other: Neurocognitive Testing; Other: CBF During Wakefulness; Other: CBF During Sleep

Interventions

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.

Also known as: Polysomnography

Controls; Obstructive Sleep Apnea Syndrome (OSAS)

Neurocognitive Testing OTHER

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

Controls; Obstructive Sleep Apnea Syndrome (OSAS)

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.

Also known as: Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Daytime/Wakefulness)

Controls; Obstructive Sleep Apnea Syndrome (OSAS)

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.

Also known as: Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Nighttime/Sleep)

Controls; Obstructive Sleep Apnea Syndrome (OSAS)

Eligibility Criteria

• Age: 6 Years - 12 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)
• Sampling Method: Non-Probability Sample

Study Population

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.

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.
• Previous adenotonsillectomy

Sponsors & Collaborators

• Children's Hospital of Philadelphia: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

Wakefulness; Sleep

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Arousal; Nervous System Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena

Limitations and Caveats

Recruitment and retention were affected by the COVID-19 pandemic. For example, many participants refused to come back for follow up testing during the pandemic and the access of normal controls to clinical areas was limited.

Results Point of Contact

• Title: Ignacio Tapia, MD
• Organization: University of Miami

itapia@miami.edu

3052439885

Study Officials

• Ignacio E. Tapia, MD, MS

  Children's Hospital of Philadelphia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2016
• First Posted: December 16, 2016
• Study Start: October 1, 2016
• Primary Completion: January 1, 2022
• Study Completion: January 1, 2022
• Last Updated: July 9, 2024
• Results First Posted: June 13, 2024

Record last verified: 2024-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)