Oxygen Therapy in Children and Adolescents With Down Syndrome and Obstructive Sleep Apnea

Obstructive Sleep Apnea Clinical Trial

— DOSA  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06043440
• Other study ID #: 2023P000062
• Status: Recruiting
• Phase: Phase 2
• Start date: October 24, 2023
• Est. completion date: December 27, 2027

Study information

• Verified date: February 2024
• Source: Brigham and Women's Hospital
• Contact: Oltion Sina
• Phone: 8573407909
• Email: osina[@]bwh.harvard.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 230
• Est. completion date: December 27, 2027
• Est. primary completion date: August 31, 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 5 Years to 215 Months

Eligibility

Inclusion Criteria:

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

2. Children with Obstructive Sleep Apnea (OSA) and obstructive apnea hypopnea index

(OAHI) 5-40/hour. :

3. Absence of clinically significant hypoxia defined as oxygen saturation <88% for 5 minutes or episodic desaturation to 60%.

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 without hypoventilation.

4. Oxygen flow required does not exceed 3.0 liter/minute or Fraction of Inspired Oxygen (FiO2) >40%.

5. Willingness to comply with all study procedures and be available for the 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.

Related Conditions & MeSH terms

• Apnea
• Down Syndrome
• Obstructive Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Syndrome

Intervention

Drug:
• Oxygen
Active nocturnal oxygen concentrator

Locations

Country	Name	City	State
United States	University of Michigan, Ann Arbor Hospital	Ann Arbor	Michigan
United States	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio
United States	Rainbow Babies and Children's Hospital, Case Medical Center	Cleveland	Ohio
United States	Children's Hospital of Los Angeles	Los Angeles	California
United States	East Virginia Medical Center	Norfolk	Virginia
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (9)

Lead Sponsor	Collaborator
Brigham and Women's Hospital	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

Country where clinical trial is conducted

United States, 

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* Note: There are 58 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	Baseline and 6 months
Primary	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.	Baseline and 6 months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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	Baseline and 6 Months
Secondary	Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)	Change from baseline in Cambridge Neuropsychological Test Automated Battery (CANTAB) Reaction Time (RTI)	Baseline and 6 Months
Secondary	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	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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).	Baseline and 6 Months
Secondary	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).	Baseline and 6 Months
Secondary	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)	Baseline and 6 Months
Secondary	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	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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)	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	7-day actigraphy measurement of sleep efficiency	Change from baseline in 7-day actigraphy measurement of sleep efficiency	Baseline and 6 Months
Secondary	7-day actigraphy measurement of time wake after sleep onset	Change from baseline in 7-day actigraphy measurement of time wake after sleep onset	Baseline and 6 Months
Secondary	7-day actigraphy measurement of sleep fragmentation	Change from baseline in 7-day actigraphy measurement of sleep fragmentation	Baseline and 6 Months
Secondary	7-day actigraphy measurement of total sleep duration	Change from baseline in 7-day actigraphy measurement of total sleep duration	Baseline and 6 Months
Secondary	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.	Baseline and 6 Months
Secondary	Polysomnography (PSG) percentage time of O2 <90 % parameter	Change from baseline in Polysomnography (PSG) percentage time of O2 <90 % parameter	Baseline and 6 Months
Secondary	Polysomnography (PSG) sleep apnea associated hypoxic burden parameter	Change from baseline in Polysomnography (PSG) sleep apnea associated hypoxic burden, parameter	Baseline and 6 Months
Secondary	Polysomnography (PSG) end-tidal CO2 level, parameter	Change from baseline in Polysomnography (PSG) end-tidal CO2 parameter.	Baseline and 6 Months
Secondary	Polysomnography (PSG) -based measure of sleep stages	Change from baseline in Polysomnography (PSG) -based measure of sleep stages. Range- N/A	Baseline and 6 Months
Secondary	Polysomnography (PSG) -based measure of EEG power bands	Change from baseline in Polysomnography (PSG) -based measure of EEG power bands	Baseline and 6 Months
Secondary	Polysomnography (PSG) -based measure of spindle morphology	Change from baseline in Polysomnography (PSG) -based measure of spindle morphology	Baseline and 6 Months
Secondary	Polysomnography (PSG) -based measure of spindle numbers	Change from baseline in Polysomnography (PSG) -based measure of spindle numbers	Baseline and 6 Months
Secondary	Polysomnography (PSG) -based measure of spindle density	Change from baseline in Polysomnography (PSG) -based measure of spindle density	Baseline and 6 Months
Secondary	Polysomnography (PSG) -based measure of slow wave oscillations	Change from baseline in Polysomnography (PSG) -based measure of slow wave oscillations	Baseline and 6 Months
Secondary	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)	Baseline and 6 Months
Secondary	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	Baseline and 6 Months
Secondary	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')	Baseline and 6 Months
Secondary	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	Baseline and 6 Months
Secondary	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	Baseline and 6 Months
Secondary	Left ventricular diastolic function as measured by Left atrial volume	Change from baseline in left ventricular diastolic function as measured by Left atrial volume	Baseline and 6 Months