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CBF and Childhood OSAS

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ClinicalTrials.gov Identifier: NCT02995837
Recruitment Status : Recruiting
First Posted : December 16, 2016
Last Update Posted : December 26, 2017
Sponsor:
Collaborator:
National Heart, Lung, and Blood Institute (NHLBI)
Information provided by (Responsible Party):
Children's Hospital of Philadelphia

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.

Condition or disease Intervention/treatment
Obstructive Sleep Apnea Syndrome Other: Sleep Study Other: Neurocognitive Testing Other: CBF During Wakefulness Other: CBF During Sleep

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.


Study Type : Observational
Estimated Enrollment : 140 participants
Observational Model: Case-Control
Time Perspective: Prospective
Official Title: Cerebral Blood Flow and Neurocognition in Children With Obstructive Sleep Apnea
Study Start Date : September 2016
Estimated Primary Completion Date : September 2019
Estimated Study Completion Date : September 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Sleep Apnea

Group/Cohort Intervention/treatment
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
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 Name: Polysomnography

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

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

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.
Other Name: Cerebral Blood Flow Testing During Hypercapneic Ventilatory Response (Nighttime/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
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 Name: Polysomnography

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

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

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




Primary Outcome Measures :
  1. Difference in cerebral blood flow (CBF) at baseline between OSAS and controls [ Time Frame: Up to 24 hours ]
    To determine whether children with OSAS have impaired blood flow regulation elicited by hypercapneic challenge compared to normal controls.


Secondary Outcome Measures :
  1. Comparison of the change in CBF from baseline to study completion between OSAS and control subjects [ Time Frame: Up to 12 Months ]
    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.


Other Outcome Measures:
  1. Determine the association between CBF regulation and severity of OSAS [ Time Frame: Up to 12 months ]
  2. Determine the association between cognitive and behavioral measurements and severity of OSAS [ Time Frame: Up to 12 months ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   6 Years to 12 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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.
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02995837


Contacts
Contact: Ignacio E. Tapia, MD, MS 267-426-1238 tapia@email.chop.edu
Contact: Mary Anne Cornaglia 267-426-5748 cornaglia@email.chop.edu

Locations
United States, Pennsylvania
Children's Hospital of Philadelphia Recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Ignacio E. Tapia, MD, MS    267-426-1238    tapia@email.chop.edu   
Sub-Investigator: Daniel J. Licht, MD         
Sub-Investigator: Carole L. Marcus, MBBCh         
Sub-Investigator: Jerilynn Radcliffe, PhD         
Sponsors and Collaborators
Children's Hospital of Philadelphia
National Heart, Lung, and Blood Institute (NHLBI)
Investigators
Principal Investigator: Ignacio E. Tapia, MD, MS Children's Hospital of Philadelphia

Responsible Party: Children's Hospital of Philadelphia
ClinicalTrials.gov Identifier: NCT02995837     History of Changes
Other Study ID Numbers: 16-012750
K01HL130719 ( U.S. NIH Grant/Contract )
First Posted: December 16, 2016    Key Record Dates
Last Update Posted: December 26, 2017
Last Verified: December 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Children's Hospital of Philadelphia:
Obstructive Sleep Apnea Syndrome
Cerebral Blood Flow
Neurocognition

Additional relevant MeSH terms:
Sleep Apnea Syndromes
Sleep Apnea, Obstructive
Apnea
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Sleep Disorders, Intrinsic
Dyssomnias
Sleep Wake Disorders
Nervous System Diseases