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

• Sponsor: Brigham and Women's Hospital (Other)
• Overall Status: Not yet recruiting
• CT.gov ID: NCT06043440
• Collaborator: Children's Hospital Medical Center, Cincinnati (Other), Children's Hospital of Philadelphia (Other), Rainbow Babies and Children's Hospital (Other), University of Michigan (Other), Children's Hospital Los Angeles (Other), Children's Hospital of The King's Daughters (Other), Seattle Children's Hospital (Other), University of Southern California (Other)
• Enrollment: 230
• Locations: 7
• Arms: 2
• Anticipated Duration (Months): 51
• Patients Per Site: 32.9
• Patients Per Site Per Month: 0.6

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Down Syndrome; Obstructive Sleep Apnea	Drug: Oxygen	Phase 2

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 Design

• Study Type: Interventional
• Anticipated Enrollment: 230 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized Control Trial of Oxygen Therapy in Children and Adolescents With Down Syndrome and Obstructive Sleep Apnea
• Anticipated Study Start Date: Sep 27, 2023
• Anticipated Primary Completion Date: Aug 31, 2027
• Anticipated Study Completion Date: Dec 27, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Oxygen plus supportive care (OXT) Nocturnal oxygen therapy plus providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.	Drug: Oxygen; Active nocturnal oxygen concentrator
No Intervention: Supportive care (SC) Providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.

Outcome Measures

Primary Outcome Measures

1. 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.

2. 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

1. 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.

2. 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.

3. 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.

4. 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.

5. 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

6. 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)

7. 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

8. 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.

9. 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).

10. 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).

11. 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)

12. 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

13. 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.

14. 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.

15. 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)

16. 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.

17. 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.

18. 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.

19. 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.

20. 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.

21. 7-day actigraphy measurement of sleep efficiency [Baseline and 6 Months]

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

22. 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

23. 7-day actigraphy measurement of sleep fragmentation [Baseline and 6 Months]

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

24. 7-day actigraphy measurement of total sleep duration [Baseline and 6 Months]

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

25. 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.

26. Polysomnography (PSG) percentage time of O2 <90 % parameter [Baseline and 6 Months]

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

27. Polysomnography (PSG) sleep apnea associated hypoxic burden parameter [Baseline and 6 Months]

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

28. Polysomnography (PSG) end-tidal CO2 level, parameter [Baseline and 6 Months]

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

29. 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

30. Polysomnography (PSG) -based measure of EEG power bands [Baseline and 6 Months]

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

31. Polysomnography (PSG) -based measure of spindle morphology [Baseline and 6 Months]

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

32. Polysomnography (PSG) -based measure of spindle numbers [Baseline and 6 Months]

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

33. Polysomnography (PSG) -based measure of spindle density [Baseline and 6 Months]

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

34. Polysomnography (PSG) -based measure of slow wave oscillations [Baseline and 6 Months]

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

35. 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)

36. 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

37. 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')

38. 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

39. 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

40. 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

Eligibility Criteria

Criteria

• Ages Eligible for Study: 5 Years to 215 Months
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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:

5. Oxygen saturation nadir >92% and

6. Decrease in obstructive index < 5 / hour or by > 50% from screening PSG

7. Reaching an optimum oxygen flow, which is defined as the flow that achieves the lowest level of AHI without hypoventilation.

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

9. Willingness to comply with all study procedures and be available for the duration of study.

10. 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
2	University of Michigan, Ann Arbor Hospital	Ann Arbor	Michigan	United States	48109
3	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
4	Rainbow Babies and Children's Hospital, Case Medical Center	Cleveland	Ohio	United States	44106
5	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
6	East Virginia Medical Center	Norfolk	Virginia	United States	23507
7	Seattle Children's Hospital	Seattle	Washington	United States	98105

Sponsors and Collaborators

• Brigham and Women's Hospital
• Children's Hospital Medical Center, Cincinnati
• Children's Hospital of Philadelphia
• Rainbow Babies and Children's Hospital
• University of Michigan
• Children's Hospital Los Angeles
• Children's Hospital of The King's Daughters
• Seattle Children's Hospital
• University of Southern California

Investigators

• Principal Investigator: Susan Redline, Brigham and Women's Hospital
• Principal Investigator: Raouf Amin, Children's Hospital Medical Center, Cincinnati

Study Documents (Full-Text)

None provided.

More Information

Publications

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• Responsible Party: Susan Redline, Proffesor, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT06043440
• Other Study ID Numbers: 2023P000062
• First Posted: Sep 21, 2023
• Last Update Posted: Sep 26, 2023
• Last Verified: Sep 1, 2023

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes
• Additional relevant MeSH terms: Apnea; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Down Syndrome; Syndrome

Study Results

No Results Posted as of Sep 26, 2023