Down Syndrome Obstructive Sleep Apnea

Phase 2RecruitingNCT06043440

Brigham and Women's Hospital230 enrolled

Overview

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).

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

230

Conditions

Down Syndrome Obstructive Sleep Apnea

Interventions

OxygenDRUG

Active nocturnal oxygen concentrator

Eligibility

Sex: ALLMin age: 5 YearsMax age: 18 Years

Medical Language ↔ Plain English

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.

Locations (7)

Children's Hospital of Los Angeles

Los Angeles, California, United States

RECRUITING

University of Michigan, Ann Arbor Hospital

Ann Arbor, Michigan, United States

RECRUITING

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio, United States

Outcomes

Primary Outcomes

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

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.

Time frame: Baseline and 6 months

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

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.

Time frame: Baseline and 6 months

Secondary Outcomes

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

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.

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

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.

Central Contacts

Oltion Sina

CONTACT

8573407909 osina@bwh.harvard.edu

Suzie Hicks

CONTACT

5136364944 suzanna.hicks@cchmc.org

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Rainbow Babies and Children's Hospital, Case Medical Center

Cleveland, Ohio, United States

RECRUITING

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, United States

RECRUITING

East Virginia Medical Center

Norfolk, Virginia, United States

RECRUITING

Seattle Children's Hospital

Seattle, Washington, United States

RECRUITING

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

Change from baseline in 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

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

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

KIDSCREEN-27 T-score

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

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

Presence of right ventricular hypertension

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)

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

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

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.

Time frame: Baseline and 6 Months

7-day actigraphy measurement of sleep efficiency

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

Time frame: Baseline and 6 Months

7-day actigraphy measurement of time wake after sleep onset

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

Time frame: Baseline and 6 Months

7-day actigraphy measurement of sleep fragmentation

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

Time frame: Baseline and 6 Months

7-day actigraphy measurement of total sleep duration

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) AHI parameter

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) sleep apnea associated hypoxic burden parameter

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) end-tidal CO2 level, parameter

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) -based measure of sleep stages

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) -based measure of EEG power bands

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) -based measure of spindle morphology

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) -based measure of spindle numbers

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) -based measure of spindle density

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

Time frame: Baseline and 6 Months

Polysomnography (PSG) -based measure of slow wave oscillations

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

Left ventricular diastolic function as measured by E wave deceleration time

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

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

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

Time frame: Baseline and 6 Months

Left ventricular diastolic function as measured by Left atrial volume

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

Time frame: Baseline and 6 Months