Down Syndrome Obstructive Sleep Apnea (DOSA)

Mass General Brigham

Status and phase: Enrolling; Phase 2

Conditions: Down Syndrome; Obstructive Sleep Apnea

Treatments: Drug: Oxygen

Study type: Interventional

Funder types: Other

Identifiers

NCT06043440

2023P000062

Details and patient eligibility

About

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).

Full 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).

Enrollment: 230 estimated patients

Sex: All

Ages: 5 to 18 years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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230 participants in 2 patient groups

Oxygen plus supportive care (OXT)

Active Comparator group

Description:

Nocturnal oxygen therapy plus providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.

Treatment:

Drug: Oxygen

Supportive care (SC)

No Intervention group

Description:

Providing patient with healthy sleep habits materials, healthy diet materials and nasal dilators.