Randomized Control Trial of oxygen therapy in Children and Adolescents with Down Syndrome and Obstructive Sleep Apnea

ABSTRACT:
A large percentage of children with Down Syndrome (DS) have obstructive sleep apnea (OSA) that is
suboptimally treated by first-line surgical interventions. The persistence of OSA-related nightly intermittent
hypoxemia and fragmented sleep may contribute to a cognitive impairment, as well as pulmonary vascular
disease, myocardial dysfunction, reduced quality of life and daily functional impairment. While oxygen is
sometimes used when other OSA therapies fail, its efficacy and safety have not been systematically studied.
This R61/R33 is therefore designed to test the hypothesis that individuals with DS and moderate to severe OSA
will have a safe and favorable response to low-flow oxygen treatment due to its effects on directly attenuating
hypoxic episodes, with subsequent increased ventilatory stability and improvement in OSA. We further
hypothesize that oxygen supplementation will lead to improvement in neurocognition, cardiac function, sleep,
and quality of life. The R61 phase will actively engage families of patients with DS and our multi-stakeholder
team to refine and pilot the protocol and recruitment strategies to ensure that we meet our recruitment/retention
milestones in the R33 phase and we generate data most relevant to our patient population. In toto, we will
screen approximately 328 children with DS and moderate to severe OSA, 5-17 yrs of age, who failed
adenotonsillectomy, to identify oxygen responders, and then randomize 230 children to oxygen plus conservative
therapy (OXT; administered using a patient-specific dose) or conservative therapy (CT) alone (weight
management, sleep hygiene, nasal dilators) for 6 months. The primary outcome of the trial is working memory
measured by co-primary endpoints that respectively assess caregiver-reported and objectively measured
functions. Secondary outcomes include cardiac function and structure, right ventricular pressure, quality of life
and sleep measures that will be collected under the supervision of experienced, central core laboratories. Six
clinical sites experienced with pediatric clinical trials and established DS centers will participate in the trial. A
Data Coordinating Center experienced with pediatric sleep trials with a strong history of working with these
clinical sites will implement and monitor data quality control processes that addresses all stages of data handling.
This study will fill a key knowledge gap in a potentially efficacious therapy for OSA, and provide evidence to
support (or refute) the use of supplemental oxygen, as well as identify physiological markers to potentially identify
patient subgroups most likely to experience benefit from this therapy.

Grant Number: 3R33HL165366-03S1
NIH Institute/Center: NIH
Principal Investigator: Raouf Amin