Down Syndrome Obstructive Sleep Apnea

Phase 2

Recruiting

• Conditions: Down Syndrome; Obstructive Sleep Apnea
• Interventions: Drug: Oxygen

• Registration Number: NCT06043440
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

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).

Detailed Description

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).

Study Timeline

• Study First Submitted: 2023-08-17
• Study First Submitted QC: 2023-09-12
• Study First Posted: 2023-09-21
• Study Start: 2023-10-24
• Status Verified: 2025-04
• Last Update Submitted: 2025-04-18
• Last Update Posted: 2025-04-20
• Primary Completion: 2027-11-30
• Study Completion: 2027-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 230

Inclusion Criteria

1. Ages 5.0 to 17.9 years at the time of screening

2. Children with OSA and obstructive apnea hypopnea index (OAHI) ≥5/hour.

3. 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.

4. Favorable response to oxygen therapy (allowing randomization) will be defined as follows:

   1. Oxygen saturation nadir >92% and
   2. Decrease in obstructive index < 5 / hour or by > 50% from screening PSG
   3. 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.
   4. Oxygen flow required does not exceed 3.0 LPM and does not exceed a FiO2 > 40 %.

5. Willingness to comply with all study procedures and available for duration of study.

6. At baseline the participant attempts to perform the neuropsychological tests

Exclusion Criteria

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oxygen plus supportive care (OXT)	Oxygen	Nocturnal oxygen therapy plus providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.

Primary Outcome Measures

Name	Time	Method
Behavior Rating Inventory of Executive Function 2 (BRIEF2) working memory score	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.
Differential Ability Scales - 2nd Edition (DAS-II) T-score.	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 Outcome Measures

Name	Time	Method
Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Total raw score	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.
Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Non Verbal raw score	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.
Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Verbal raw score	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.
Child Behavior Checklist (CBCL) T-scores for domains (Internalizing, Externalizing, Total Problems).	Baseline and 6 Months	Change from baseline in Child Behavior Checklist (CBCL) T-scores for domains (Internalizing, Externalizing, Total Problems).
Child Behavior Checklist (CBCL) T-scores for subscales (Attention Problems, Thought Problems, Rule-Breaking Behaviors, Aggressive Behaviors)	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)
KIDSCREEN-27 T-score	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
Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance T-score	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.
Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score	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.
Presence of right ventricular hypertension	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)
Wechsler Intelligence Scale (WISC) for Children 5th edition (WISC-5) Cancellation raw score	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.
Wechsler Preschool and Primary Scale of Intelligence 4th edition (WPPSI-4) Cancellation task raw score	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.
Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Behavior Regulation Index (BRI) domain.	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.
Differential Ability Scales-2 (DAS-II) Recall of Digits Forward raw score	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.
Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) adjusted total errors based on stages completed	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
Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)	Baseline and 6 Months	Change from baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)
Developmental Neuropsychological Assessment 2nd Edition (NEPSY-II) verbal fluency test raw score	Baseline and 6 Months	Change from baseline in Developmental Neuropsychological Assessment 2nd Edition (NEPSY-II) verbal fluency test raw score. Range-N/A
Observer Memory Questionnaire - Parent Form (OMQ-PF) total T-score	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.
Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for subscales (Inhibit, Self-Monitor, Shift, Emotional Control, Initiate)	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).
7-day actigraphy measurement of sleep fragmentation	Baseline and 6 Months	Change from baseline in 7-day actigraphy measurement of sleep fragmentation
Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Emotional Recognition Index (ERI) domain.	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.
Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Cognitive Regulation Index (CRI) domain.	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.
7-day actigraphy measurement of sleep efficiency	Baseline and 6 Months	Change from baseline in 7-day actigraphy measurement of sleep efficiency
7-day actigraphy measurement of time wake after sleep onset	Baseline and 6 Months	Change from baseline in 7-day actigraphy measurement of time wake after sleep onset
7-day actigraphy measurement of total sleep duration	Baseline and 6 Months	Change from baseline in 7-day actigraphy measurement of total sleep duration
Polysomnography (PSG) AHI parameter	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.
Polysomnography (PSG) percentage time of O2 <90 % parameter	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) percentage time of O2 \<90 % parameter
Polysomnography (PSG) sleep apnea associated hypoxic burden parameter	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) sleep apnea associated hypoxic burden, parameter
Polysomnography (PSG) end-tidal CO2 level, parameter	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) end-tidal CO2 parameter.
Polysomnography (PSG) -based measure of sleep stages	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) -based measure of sleep stages. Range- N/A
Polysomnography (PSG) -based measure of EEG power bands	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) -based measure of EEG power bands
Polysomnography (PSG) -based measure of spindle morphology	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) -based measure of spindle morphology
Polysomnography (PSG) -based measure of spindle numbers	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) -based measure of spindle numbers
Polysomnography (PSG) -based measure of spindle density	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) -based measure of spindle density
Left ventricular diastolic function as measured by E wave deceleration time	Baseline and 6 Months	Change from baseline in left ventricular diastolic function as measured by E wave deceleration time
Left ventricular diastolic function as measured by Mitral septal and lateral e' and a' (E/e')	Baseline and 6 Months	Change from baseline in left ventricular diastolic function as measured by Mitral septal and lateral e' and a' (E/e')
Polysomnography (PSG) -based measure of slow wave oscillations	Baseline and 6 Months	Change from baseline in Polysomnography (PSG) -based measure of slow wave oscillations
Left ventricular diastolic function as measured by Left atrial volume	Baseline and 6 Months	Change from baseline in left ventricular diastolic function as measured by Left atrial volume
Left ventricular diastolic function as measured by Mitral E and A wave (E:A ratio)	Baseline and 6 Months	Change from baseline in left ventricular diastolic function as measured by Mitral E and A wave (E:A ratio)
Left ventricular diastolic function as measured by Mitral lateral tissue Doppler isovolumic relaxation time	Baseline and 6 Months	Change from baseline in left ventricular diastolic function as measured by Mitral lateral tissue Doppler isovolumic relaxation time
Left ventricular diastolic function as measured by Pulmonary vein A wave reversal duration	Baseline and 6 Months	Change from baseline in left ventricular diastolic function as measured by Pulmonary vein A wave reversal duration

Trial Locations

Locations (7)

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Children's Hospital of Los Angeles; 🇺🇸 Los Angeles, California, United States

Seattle Children's Hospital; 🇺🇸 Seattle, Washington, United States

Rainbow Babies and Children's Hospital, Case Medical Center; 🇺🇸 Cleveland, Ohio, United States

Cincinnati Children's Hospital Medical Center; 🇺🇸 Cincinnati, Ohio, United States

University of Michigan, Ann Arbor Hospital; 🇺🇸 Ann Arbor, Michigan, United States

East Virginia Medical Center; 🇺🇸 Norfolk, Virginia, United States