Clinical trial NCT06043440: Down Syndrome Obstructive Sleep Apnea
Official title: Randomized Control Trial of Oxygen Therapy in Children and Adolescents With Down Syndrome and Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Down Syndrome
Obstructive Sleep Apnea
Lead sponsor: Brigham and Women's Hospital
Sponsor class: OTHER
Collaborators: name: Children's Hospital Medical Center, Cincinnati
name: Children's Hospital of Philadelphia
name: Rainbow Babies and Children's Hospital
name: University of Michigan
name: Children's Hospital Los Angeles
name: Children's Hospital of The King's Daughters
name: Seattle Children's Hospital
name: University of Southern California
First posted: 2023-09-21
Enrollment: 230
Sex: ALL
Minimum age (years): 5
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

Eligibility criteria: 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.

Primary outcomes:
measure: Behavior Rating Inventory of Executive Function 2 (BRIEF2) working memory score
timeFrame: Baseline and 6 months
measure: Differential Ability Scales - 2nd Edition (DAS-II) T-score.
timeFrame: Baseline and 6 months
Secondary outcomes:
measure: Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Total raw score
timeFrame: Baseline and 6 Months
measure: Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Verbal raw score
timeFrame: Baseline and 6 Months
measure: Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Non Verbal raw score
timeFrame: Baseline and 6 Months
measure: Differential Ability Scales-2 (DAS-II) Recall of Digits Forward raw score
timeFrame: Baseline and 6 Months
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) adjusted total errors based on stages completed
timeFrame: Baseline and 6 Months
measure: Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)
timeFrame: Baseline and 6 Months
measure: Developmental Neuropsychological Assessment 2nd Edition (NEPSY-II) verbal fluency test raw score
timeFrame: Baseline and 6 Months
measure: Observer Memory Questionnaire - Parent Form (OMQ-PF) total T-score
timeFrame: Baseline and 6 Months
measure: Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for subscales (Inhibit, Self-Monitor, Shift, Emotional Control, Initiate)
timeFrame: Baseline and 6 Months
measure: Child Behavior Checklist (CBCL) T-scores for domains (Internalizing, Externalizing, Total Problems).
timeFrame: Baseline and 6 Months
measure: Child Behavior Checklist (CBCL) T-scores for subscales (Attention Problems, Thought Problems, Rule-Breaking Behaviors, Aggressive Behaviors)
timeFrame: Baseline and 6 Months
measure: KIDSCREEN-27 T-score
timeFrame: Baseline and 6 Months
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance T-score
timeFrame: Baseline and 6 Months
measure: Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score
timeFrame: Baseline and 6 Months
measure: Presence of right ventricular hypertension
timeFrame: Baseline and 6 Months
measure: Wechsler Intelligence Scale (WISC) for Children 5th edition (WISC-5) Cancellation raw score
timeFrame: Baseline and 6 Months
measure: Wechsler Preschool and Primary Scale of Intelligence 4th edition (WPPSI-4) Cancellation task raw score
timeFrame: Baseline and 6 Months
measure: Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Behavior Regulation Index (BRI) domain.
timeFrame: Baseline and 6 Months
measure: Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Emotional Recognition Index (ERI) domain.
timeFrame: Baseline and 6 Months
measure: Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Cognitive Regulation Index (CRI) domain.
timeFrame: Baseline and 6 Months
measure: 7-day actigraphy measurement of sleep efficiency
timeFrame: Baseline and 6 Months
measure: 7-day actigraphy measurement of time wake after sleep onset
timeFrame: Baseline and 6 Months
measure: 7-day actigraphy measurement of sleep fragmentation
timeFrame: Baseline and 6 Months
measure: 7-day actigraphy measurement of total sleep duration
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) AHI parameter
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) percentage time of O2 <90 % parameter
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) sleep apnea associated hypoxic burden parameter
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) end-tidal CO2 level, parameter
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) -based measure of sleep stages
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) -based measure of EEG power bands
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) -based measure of spindle morphology
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) -based measure of spindle numbers
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) -based measure of spindle density
timeFrame: Baseline and 6 Months
measure: Polysomnography (PSG) -based measure of slow wave oscillations
timeFrame: Baseline and 6 Months
measure: Left ventricular diastolic function as measured by Mitral E and A wave (E:A ratio)
timeFrame: Baseline and 6 Months
measure: Left ventricular diastolic function as measured by E wave deceleration time
timeFrame: Baseline and 6 Months
measure: Left ventricular diastolic function as measured by Mitral septal and lateral e' and a' (E/e')
timeFrame: Baseline and 6 Months
measure: Left ventricular diastolic function as measured by Mitral lateral tissue Doppler isovolumic relaxation time
timeFrame: Baseline and 6 Months
measure: Left ventricular diastolic function as measured by Pulmonary vein A wave reversal duration
timeFrame: Baseline and 6 Months
measure: Left ventricular diastolic function as measured by Left atrial volume
timeFrame: Baseline and 6 Months
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Hospital of Los Angeles
state: California
city: Ann Arbor
country: United States
facility: University of Michigan, Ann Arbor Hospital
state: Michigan
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Rainbow Babies and Children's Hospital, Case Medical Center
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Norfolk
country: United States
facility: East Virginia Medical Center
state: Virginia
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
Study officials:
affiliation: Brigham and Women's Hospital
name: Susan Redline
role: PRINCIPAL_INVESTIGATOR
affiliation: Children's Hospital Medical Center, Cincinnati
name: Raouf Amin
role: PRINCIPAL_INVESTIGATOR
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