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NCT Number: NCT06043440

Down Syndrome Obstructive Sleep Apnea

The purpose of this study is to assess whether oxygen supplementation during sleep improves working memory and other clinical and patient-reported outcomes among children who have Down Syndrome (DS) with moderate to severe Obstructive Sleep Apnea (OSA).

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Key information

Conditions

Down Syndrome Abnormalities, Multiple Apnea Chromosome Disorders Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Dyssomnias Genetic Diseases, Inborn Intellectual Disability Nervous System Diseases Neurobehavioral Manifestations Neurologic Manifestations Obstructive Sleep Apnea Respiration Disorders Respiratory Tract Diseases Sleep Apnea Syndromes Sleep Apnea, Obstructive Sleep Disorders, Intrinsic Sleep Wake Disorders

Age range

5 year–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Children's Hospital of Los Angeles, Los Angeles, California, United States

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About this study

This will be a randomized, single-blind 6-month Phase-2 clinical trial that compares the impact of oxygen therapy during sleep on measures of cognition, behavior, quality of life, cardiac structure and function, and sleep in children with Down Syndrome(DS) with moderate to severe obstructive sleep apnea.

The proposed study will involve participation of children and their caregivers. Children will be recruited from each site's sleep clinics and laboratories, Down syndrome clinics and otolaryngology clinics. Community recruitment will be coordinated with local Down Syndrome Associations.

Children who agree to participate in the study will be screened for eligibility based on history, physical examination, and review of medical records including history of congenital heart disease and Pulmonary Hypertension (PHTN), and use of Continuous Positive Airway Pressure (CPAP). Children eligible for the study are those with persistent obstructive apnea after adenotonsillectomy or children with obstructive sleep apnea without adenotonsillar hypertrophy or in situations when parents refuse adenotonsillectomy.. The enrollment PSG eligibility will be determined by central scoring of either a research Polysomnography (PSG). In addition to an oxygen titration PSG, which determines responsiveness to oxygen, participants will be asked to wear a wrist actigraph and undergo neurocognitive testing, echocardiography, physical examination, anthropometry, and venipuncture. Caregivers will complete questionnaires to assess their child's emotional, physical, social, and school functioning, sleep quality; child's behavior and cognitive function, and will complete a sleep diary that is used concurrently with their child's use of a wrist actigraph. The latter includes caregiver completion of the "Behavior Rating Inventory of Executive Function" (BRIEF2), a co-primary outcome.

At 3 months, caregivers will complete the BRIEF2. At 6 months, all baseline studies and a PSG will be repeated.

At baseline, demographic data will be collected, including information on residential address (for use in geocoding).

Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Ages 5.0 to 17.9 years at the time of screening
  • Children with OSA and obstructive apnea hypopnea index (OAHI) ≥5/hour.
  • Absence of clinically significant hypoxia defined as oxygen saturation <88% for 5 minutes or episodic desaturation to 60% as these levels would otherwise identify children eligible to routinely receive oxygen.
  • Favorable response to oxygen therapy (allowing randomization) will be defined as follows:
  • Oxygen saturation nadir >92% and
  • Decrease in obstructive index < 5 / hour or by > 50% from screening PSG
  • Reaching an optimum oxygen flow which is defined as the flow that achieves the lowest level of AHI with maximum CO2 level less than 65 mmHg observed for 5 consecutive minutes and or an increase in CO2 by less than 15 points above baseline. The above criteria are observed while the patient spends a minimal of 30 minutes in the supine position and at least one cycle of rapid eye movement (REM) sleep.
  • Oxygen flow required does not exceed 3.0 LPM and does not exceed a FiO2 > 40 %.
  • Willingness to comply with all study procedures and available for duration of study.
  • At baseline the participant attempts to perform the neuropsychological tests

Exclusion criteria

  • Current CPAP use with documented compliance(> 4 hrs/ night; > 70% of nights).
  • Oxygen saturation < 90% at rest during wakefulness.
  • Chronic daytime or nighttime use of supplemental oxygen.
  • Smoker in the child's bedroom.
  • Unrepaired congenital heart disease.
  • Moderate to severe pulmonary hypertension requiring treatment with oxygen and or pulmonary vasodilator.
  • Unable to participate in a PSG.
  • Individuals who develop alveolar hypoventilation with oxygen as previously defined.
  • Other severe chronic diseases determined by their provider as making them poor study candidates.
  • Enrolled or planning to enroll in another study that may conflict with protocol requirements or confound results in this trial.
  • Documented clinically significant untreated hypothyroidism
  • Children with adenotonsillar hypertrophy who are candidates for adenotonsillectomy and parents agree to the surgery.

Treatment and study plan

Oxygen

Drug

Active nocturnal oxygen concentrator

Primary outcomes

  1. Behavior Rating Inventory of Executive Function 2 (BRIEF2) working memory score

    Time frame: Baseline and 6 months

    Change from baseline in the Behavior Rating Inventory of Executive Function 2 (BRIEF2) working memory score (BRIEF2wm). The score ranges from 35-90. A higher score is a worse outcome.

  2. Differential Ability Scales - 2nd Edition (DAS-II) T-score.

    Time frame: Baseline and 6 months

    Change from baseline in the Differential Ability Scales - 2nd Edition (DAS-II) recognition of pictures (DAS2RoP) T-score. The score ranges from 10-90. A higher score is a better outcome.

Secondary outcomes

  1. Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Total raw score

    Time frame: Baseline and 6 Months

    Change from baseline of Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Total raw score. The score ranges from 0-64. A higher score is a better outcome.

  2. Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Verbal raw score

    Time frame: Baseline and 6 Months

    Change from baseline of Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Verbal raw score. The score ranges from 0-30. A higher score is a better outcome.

  3. Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Non Verbal raw score

    Time frame: Baseline and 6 Months

    Change from baseline of Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Non Verbal raw score. The score ranges from 0-34. A higher score is a better outcome.

  4. Differential Ability Scales-2 (DAS-II) Recall of Digits Forward raw score

    Time frame: Baseline and 6 Months

    Change from baseline in Differential Ability Scales-2 (DAS-II) Recall of Digits Forward raw score. The score ranges from 0-38. A higher score is a better outcome.

  5. Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) adjusted total errors based on stages completed

    Time frame: Baseline and 6 Months

    Change from baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) adjusted total errors based on stages completed

  6. Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)

    Time frame: Baseline and 6 Months

    Change from baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)

  7. Developmental Neuropsychological Assessment 2nd Edition (NEPSY-II) verbal fluency test raw score

    Time frame: Baseline and 6 Months

    Change from baseline in Developmental Neuropsychological Assessment 2nd Edition (NEPSY-II) verbal fluency test raw score. Range-N/A

  8. Observer Memory Questionnaire - Parent Form (OMQ-PF) total T-score

    Time frame: Baseline and 6 Months

    Change from baseline in Observer Memory Questionnaire - Parent Form (OMQ-PF) total T-score. The score ranges from 0-135. A higher score is a better outcome.

  9. Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for subscales (Inhibit, Self-Monitor, Shift, Emotional Control, Initiate)

    Time frame: Baseline and 6 Months

    Change from baseline in Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for subscales (Inhibit, Self-Monitor, Shift, Emotional Control, Initiate).

  10. Child Behavior Checklist (CBCL) T-scores for domains (Internalizing, Externalizing, Total Problems).

    Time frame: Baseline and 6 Months

    Change from baseline in Child Behavior Checklist (CBCL) T-scores for domains (Internalizing, Externalizing, Total Problems).

  11. Child Behavior Checklist (CBCL) T-scores for subscales (Attention Problems, Thought Problems, Rule-Breaking Behaviors, Aggressive Behaviors)

    Time frame: Baseline and 6 Months

    Change from baseline in Child Behavior Checklist (CBCL) T-scores for subscales (Attention Problems, Thought Problems, Rule-Breaking Behaviors, Aggressive Behaviors)

  12. KIDSCREEN-27 T-score

    Time frame: Baseline and 6 Months

    Change from baseline in KIDSCREEN-27 T-score, including domains of: physical well-being; psychological well-being; autonomy and parent relations; social support and peers; school environment. Range-N/A

  13. Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance T-score

    Time frame: Baseline and 6 Months

    Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance T-score. The score ranges from 28.7-85.6. A higher score is a worse outcome.

  14. Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score

    Time frame: Baseline and 6 Months

    Change from baseline in Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score. The score ranges from 37.9-86.6. A higher score is a worse outcome.

  15. Presence of right ventricular hypertension

    Time frame: Baseline and 6 Months

    Presence of right ventricular hypertension as measured by tricuspid regurgitation continuous wave peak velocity (defined as a ratio of pulmonary artery pressure / systolic arterial pressure (PAP/SAP) >1/3); interventricular septal flattening as measured by eccentricity index (defined as systolic ratio of >1.25)

  16. Wechsler Intelligence Scale (WISC) for Children 5th edition (WISC-5) Cancellation raw score

    Time frame: Baseline and 6 Months

    Change from baseline of Wechsler Intelligence Scale (WISC) for Children 5th edition (WISC-5) Cancellation raw score. The score ranges from 0-128. A higher score is a better outcome.

  17. Wechsler Preschool and Primary Scale of Intelligence 4th edition (WPPSI-4) Cancellation task raw score

    Time frame: Baseline and 6 Months

    Change from baseline in Wechsler Preschool and Primary Scale of Intelligence 4th edition (WPPSI-4) Cancellation task raw score (if unable to complete Wechsler Intelligence Scale 5th edition Cancellation test). The score ranges from 0-96. A higher score is a better outcome.

  18. Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Behavior Regulation Index (BRI) domain.

    Time frame: Baseline and 6 Months

    Change from baseline in Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Behavior Regulation Index (BRI) domain. The score ranges from 35-90. A higher score is a worse outcome.

  19. Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Emotional Recognition Index (ERI) domain.

    Time frame: Baseline and 6 Months

    Change from baseline in Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Emotional Recognition Index (ERI) domain. The score ranges from 35-90. A higher score is a worse outcome.

  20. Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Cognitive Regulation Index (CRI) domain.

    Time frame: Baseline and 6 Months

    Change from baseline in Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Cognitive Regulation Index (CRI) domain. The score ranges from 35-90. A higher score is a worse outcome.

  21. 7-day actigraphy measurement of sleep efficiency

    Time frame: Baseline and 6 Months

    Change from baseline in 7-day actigraphy measurement of sleep efficiency

  22. 7-day actigraphy measurement of time wake after sleep onset

    Time frame: Baseline and 6 Months

    Change from baseline in 7-day actigraphy measurement of time wake after sleep onset

  23. 7-day actigraphy measurement of sleep fragmentation

    Time frame: Baseline and 6 Months

    Change from baseline in 7-day actigraphy measurement of sleep fragmentation

  24. 7-day actigraphy measurement of total sleep duration

    Time frame: Baseline and 6 Months

    Change from baseline in 7-day actigraphy measurement of total sleep duration

  25. Polysomnography (PSG) AHI parameter

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) AHI parameter. The score ranges from 0- >40. A higher score is a worse outcome.

  26. Polysomnography (PSG) percentage time of O2 <90 % parameter

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) percentage time of O2 <90 % parameter

  27. Polysomnography (PSG) sleep apnea associated hypoxic burden parameter

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) sleep apnea associated hypoxic burden, parameter

  28. Polysomnography (PSG) end-tidal CO2 level, parameter

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) end-tidal CO2 parameter.

  29. Polysomnography (PSG) -based measure of sleep stages

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) -based measure of sleep stages. Range- N/A

  30. Polysomnography (PSG) -based measure of EEG power bands

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) -based measure of EEG power bands

  31. Polysomnography (PSG) -based measure of spindle morphology

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) -based measure of spindle morphology

  32. Polysomnography (PSG) -based measure of spindle numbers

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) -based measure of spindle numbers

  33. Polysomnography (PSG) -based measure of spindle density

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) -based measure of spindle density

  34. Polysomnography (PSG) -based measure of slow wave oscillations

    Time frame: Baseline and 6 Months

    Change from baseline in Polysomnography (PSG) -based measure of slow wave oscillations

  35. Left ventricular diastolic function as measured by Mitral E and A wave (E:A ratio)

    Time frame: Baseline and 6 Months

    Change from baseline in left ventricular diastolic function as measured by Mitral E and A wave (E:A ratio)

  36. Left ventricular diastolic function as measured by E wave deceleration time

    Time frame: Baseline and 6 Months

    Change from baseline in left ventricular diastolic function as measured by E wave deceleration time

  37. Left ventricular diastolic function as measured by Mitral septal and lateral e' and a' (E/e')

    Time frame: Baseline and 6 Months

    Change from baseline in left ventricular diastolic function as measured by Mitral septal and lateral e' and a' (E/e')

  38. Left ventricular diastolic function as measured by Mitral lateral tissue Doppler isovolumic relaxation time

    Time frame: Baseline and 6 Months

    Change from baseline in left ventricular diastolic function as measured by Mitral lateral tissue Doppler isovolumic relaxation time

  39. Left ventricular diastolic function as measured by Pulmonary vein A wave reversal duration

    Time frame: Baseline and 6 Months

    Change from baseline in left ventricular diastolic function as measured by Pulmonary vein A wave reversal duration

  40. Left ventricular diastolic function as measured by Left atrial volume

    Time frame: Baseline and 6 Months

    Change from baseline in left ventricular diastolic function as measured by Left atrial volume

Study contacts

Contact information is provided by the study sponsor or research team.

Oltion Sina

CONTACT

[email protected]

8573407909

Suzie Hicks

CONTACT

[email protected]

5136364944

Sponsors and collaborators

Lead sponsor

Brigham and Women's Hospital

Other

Collaborators

  • Children's Hospital Los Angeles
  • Children's Hospital Medical Center, Cincinnati
  • Children's Hospital of Philadelphia
  • Children's Hospital of The King's Daughters
  • Rainbow Babies and Children's Hospital
  • Seattle Children's Hospital
  • University of Michigan
  • University of Southern California

Registry information

Official study title

Randomized Control Trial of Oxygen Therapy in Children and Adolescents With Down Syndrome and Obstructive Sleep Apnea

Acronym: DOSA

Important dates

Study start
2023
Primary completion
2027
Study completion
2027
First posted
Sep 21, 2023
Registry last updated
Apr 20, 2025

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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