Randomized Control Trial of Oxygen Therapy in Children and Adolescents With Down Syndrome and Obstructive Sleep Apnea
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 230
- 试验地点
- 7
- 主要终点
- Behavior Rating Inventory of Executive Function 2 (BRIEF2) working memory score
研究概览
简要总结
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).
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 5 Years 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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.
研究组 & 干预措施
Oxygen plus supportive care (OXT)
Nocturnal oxygen therapy plus providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.
干预措施: Oxygen (Drug)
结局指标
主要结局
Behavior Rating Inventory of Executive Function 2 (BRIEF2) working memory score
时间窗: 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.
时间窗: 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.
次要结局
- Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Total raw score(Baseline and 6 Months)
- Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Non Verbal raw score(Baseline and 6 Months)
- Stanford-Binet Intelligence Scales, 5th edition (SB-5) Working Memory Verbal raw score(Baseline and 6 Months)
- Child Behavior Checklist (CBCL) T-scores for domains (Internalizing, Externalizing, Total Problems).(Baseline and 6 Months)
- Child Behavior Checklist (CBCL) T-scores for subscales (Attention Problems, Thought Problems, Rule-Breaking Behaviors, Aggressive Behaviors)(Baseline and 6 Months)
- KIDSCREEN-27 T-score(Baseline and 6 Months)
- Patient-Reported Outcomes Measurement Information System (PROMIS) sleep disturbance T-score(Baseline and 6 Months)
- Patient-Reported Outcomes Measurement Information System (PROMIS) sleep-related impairment T-score(Baseline and 6 Months)
- Presence of right ventricular hypertension(Baseline and 6 Months)
- Wechsler Intelligence Scale (WISC) for Children 5th edition (WISC-5) Cancellation raw score(Baseline and 6 Months)
- Wechsler Preschool and Primary Scale of Intelligence 4th edition (WPPSI-4) Cancellation task raw score(Baseline and 6 Months)
- Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Behavior Regulation Index (BRI) domain.(Baseline and 6 Months)
- Differential Ability Scales-2 (DAS-II) Recall of Digits Forward raw score(Baseline and 6 Months)
- Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) adjusted total errors based on stages completed(Baseline and 6 Months)
- Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)(Baseline and 6 Months)
- Developmental Neuropsychological Assessment 2nd Edition (NEPSY-II) verbal fluency test raw score(Baseline and 6 Months)
- Observer Memory Questionnaire - Parent Form (OMQ-PF) total T-score(Baseline and 6 Months)
- Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for subscales (Inhibit, Self-Monitor, Shift, Emotional Control, Initiate)(Baseline and 6 Months)
- Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Emotional Recognition Index (ERI) domain.(Baseline and 6 Months)
- Behavior Rating Inventory of Executive Function 2 (BRIEF2) T-scores for Cognitive Regulation Index (CRI) domain.(Baseline and 6 Months)
- 7-day actigraphy measurement of sleep efficiency(Baseline and 6 Months)
- 7-day actigraphy measurement of time wake after sleep onset(Baseline and 6 Months)
- 7-day actigraphy measurement of sleep fragmentation(Baseline and 6 Months)
- 7-day actigraphy measurement of total sleep duration(Baseline and 6 Months)
- Polysomnography (PSG) AHI parameter(Baseline and 6 Months)
- Polysomnography (PSG) percentage time of O2 <90 % parameter(Baseline and 6 Months)
- Polysomnography (PSG) sleep apnea associated hypoxic burden parameter(Baseline and 6 Months)
- Polysomnography (PSG) end-tidal CO2 level, parameter(Baseline and 6 Months)
- Polysomnography (PSG) -based measure of sleep stages(Baseline and 6 Months)
- Polysomnography (PSG) -based measure of EEG power bands(Baseline and 6 Months)
- Polysomnography (PSG) -based measure of spindle morphology(Baseline and 6 Months)
- Polysomnography (PSG) -based measure of spindle numbers(Baseline and 6 Months)
- Polysomnography (PSG) -based measure of spindle density(Baseline and 6 Months)
- Left ventricular diastolic function as measured by E wave deceleration time(Baseline and 6 Months)
- Left ventricular diastolic function as measured by Mitral septal and lateral e' and a' (E/e')(Baseline and 6 Months)
- Polysomnography (PSG) -based measure of slow wave oscillations(Baseline and 6 Months)
- Left ventricular diastolic function as measured by Left atrial volume(Baseline and 6 Months)
- Left ventricular diastolic function as measured by Mitral E and A wave (E:A ratio)(Baseline and 6 Months)
- Left ventricular diastolic function as measured by Mitral lateral tissue Doppler isovolumic relaxation time(Baseline and 6 Months)
- Left ventricular diastolic function as measured by Pulmonary vein A wave reversal duration(Baseline and 6 Months)
研究者
Susan Redline
Proffesor
Brigham and Women's Hospital