Trial Outcomes & Findings for A Pilot Study to Evaluate the Hypoglossal Nerve Stimulator in Adolescents With Down Syndrome and Obstructive Sleep Apnea (NCT NCT02344108)

Participants were recruited by their local otolaryngologist-investigator, many of whom were referred by Down syndrome clinical programs and other providers. National Down syndrome organizations assisted with study advertisements.

Enrollment in this study was defined at the time the informed consent forms were signed. Following enrollment, patients underwent drug-induced sleep endoscopies (DISEs) and baseline polysomnography (PSG) unless, per protocol, these procedures had been completed within a set time from enrollment. Patient medical records were reviewed in detail, along with the baseline DISE and PSG results, to confirm eligibility prior to scheduling hypoglossal nerve stimulator implantation.

A Pilot Study to Evaluate the Hypoglossal Nerve Stimulator in Adolescents With Down Syndrome and Obstructive Sleep Apnea

In this study, adverse events were defined as "serious" if they resulted in: (1) death; (2) a life-threatening experience; (3) in-patient hospitalization or prolongation of hospital stay; (4) a persistent or significant disability/incapacity; (5) congenital anomaly/birth defect; or (6) events that jeopardized the health of the subject or required surgical intervention.

Non-serious adverse events include all other adverse events recorded during the study which were determined to be related or possibly related to the device, surgery, or research. It does not include adverse events that were determined to be serious, as previously defined. Safety events that were determined to be unrelated to the study were not included in this analysis.

Unanticipated adverse device effects (UADEs) are defined as adverse events which were determined to be serious, unexpected and related or possibly related to the investigational device.

The apnea-hypopnea index (AHI) is a measure of the number of times per hour that an apnea or hypopnea event occurs during sleep. Apneas are defined as short pauses in breathing, while hypopnea is defined as shallow breathing. The AHI is useful in evaluating obstructive sleep apnea (OSA). The normal pediatric range is typically defined as an AHI of less than 1 event per hour. An AHI between 5 and 10 events per hour is consistent with moderate OSA, while an AHI above 10 suggests severe OSA. We report the mean AHI measured 1 year after device implantation. We also report the mean change in AHI, which compares AHI from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease from baseline to 1 year.

The obstructive apnea-hypopnea index is similar to the standard AHI measure, but it only includes apnea or hypopnea events that are attributable to airway obstruction, as opposed to an origin in the central nervous system (referred to as "central sleep apnea"). This value reflects the numbers of times per hour the subject experienced an obstruction-related apnea or hypopnea event during sleep. We report the mean obstructive AHI measured 1 year after device implantation. We also report the mean change in obstructive AHI, which compares obstructive AHI from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease from baseline to 1 year.

The central apnea-hypopnea index is similar to the standard AHI measure, but it only includes apnea or hypopnea events that arise from the central nervous system. Central apnea and hypopnea events are not caused by airway obstruction. This value reflects the numbers of times per hour the subject experienced a neurologically-related apnea or hypopnea event during sleep. We report the mean central apnea index measured 1 year after device implantation. We also report the mean change in central apnea index, which compares central apnea index from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease from baseline to 1 year.

The hypopnea percentage describes the relative frequency of hypopnea events versus apnea events. Hypopnea is defined as shallow breathing, while apnea is defined as short pauses in breathing. The hypopnea percentage reflects what percentage of the total AHI can be attributed to hypopneas as opposed to apneas during sleep. We report the mean hypopnea percentage measured 1 year after device implantation. We also report the mean change in hypopnea percentage, which compares hypopnea percentage from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease from baseline to 1 year.

During the overnight sleep studies, subjects' blood oxygen saturation (SpO2) were continuously monitored. This value reflects the percentage of their entire sleep time that the participants' blood oxygen saturation was below 90%. We report the mean percentage of time SpO2 \< 90% measured 1 year after device implantation. We also report the mean change in this time, which compares percentage of time from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease from baseline to 1 year.

End Tidal CO2 (ETCO2) is a measure of the carbon dioxide that is released at the end of a breath. Higher-than-normal end tidal CO2 measurements may be indicative of hypoventilation. We report here the percentage of time during sleep that subjects' end tidal CO2 exceeded the typical range of 50 mmHg. We report the mean percentage of time measured 1 year after device implantation. We also report the mean change in percentage of time ETCO2 \> 50 mmHg, which compares percentage of time from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease from baseline to 1 year.

The SpO2 nadir is the lowest blood oxygen saturation measurement taken throughout the sleep study. Change in SpO2 Nadir is defined from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease over time.

Sleep efficiency is a measure of how much time that is dedicated to sleep is actually spent sleeping. Sleep efficiency is proportional to the amount of time spent asleep divided by the amount of time dedicated to sleep. Change in sleep efficiency is defined from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease over time.

REM percentage is the percentage of sleep time that the participant spent in the rapid eye movement (REM) phase of sleep. Change in REM percentage is defined from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease over time.

The arousal index measures the number of times per hour that the participant awoke from sleep. Change in arousal index is defined from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease over time.

The OSA-18 generates from participant responses a total score between 18 and 126 which is designed to reflect the impact of obstructive sleep apnea on the pediatric patient's quality of life. Higher total scores on the OSA-18 indicate a greater, negative impact on quality of life; while lower scores indicate a lesser impact on quality of life. Interpretation of total scores is as follows: minimal OSA impact for scores under 60; moderate OSA impact for scores between 60 and 80; and severe OSA impact for scores above 80. Change in OSA-18 total survey score is defined from baseline to 1 year postoperatively; therefore, negative change scores indicate a decrease of symptom severity over time.

The OSA-18 questionnaire includes a stand-alone question that asks to rate the child's overall quality of life on a scale from 0 (indicating worst quality of life possible) to 10 (indicating best quality of life possible). Change in OSA-18 overall score is defined from baseline to 1 year postoperatively; therefore, positive change scores indicate an improvement in quality of life over time.

The ESS is a validated survey of daytime sleepiness. The ESS is scored as the sum of all items with scores ranging from 0 to 24 and higher scores indicating worse symptoms. Change ESS survey score is defined from baseline to 1 year postoperatively; therefore, negative change scores indicate an improvement in symptom severity over time.