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

The study will be a multi-center, prospective, single-arm study conducted under a common
implant and follow-up protocol. Twenty-one adolescents and young adults (10-21 years of age)
with Down Syndrome with moderate to severe obstructive sleep apnea after adenotonsillectomy
will be identified through a Multi-Disciplinary clinic for patients with Trisomy 21 at each
of our participating sites Patients and their parents will be screened by a senior
pulmonologist and pediatrician for medical clearance and willingness to participate. Subjects
will then undergo preoperative evaluation with an in-lab polysomnogram (PSG), evaluation by a
pediatric otolaryngology surgeon, and drug induced sleep endoscopy (DISE) to ensure all
inclusion and exclusion criteria are met. Subjects meeting eligibility criteria will then be
implanted with the Inspire® Upper Airway Simulation System, Model 3024 IPG, and any
subsequent iteration thereof that are approved under P130008 for the treatment of obstructive
sleep apnea, a hypoglossal nerve stimulator, after informed consent. Surgery will be
performed by senior pediatric otolaryngologists who have completed a training program for the
Inspire® system. Subjects will then adhere to a follow-up schedule. The device will be
activated and settings titrated during an in-lab sleep study 1 month postoperatively. Quality
of life surveys and device interrogation will be conducted at timed intervals. Subjects will
then undergo in-lab polysomnography at 2 months, 6 months, and 12-months, then on an annual
basis, and the device titrated as needed. All personnel adjusting device parameters will be
trained in programming the Inspire® system. For this pilot study, we will evaluate safety and
efficacy over the first year after device implantation.

Inclusion Criteria:

- Only children and young adults with Down Syndrome age 10-21 years with prior
adenotonsillectomy will be considered for the study.

- Subjects must have BMI <95th percentile for age

- All subjects must have moderate to severe OSA (AHI >10, AHI <50, no more than 25% AHI
attributable to central events) based on prior in-lab polysomnography performed after
adenotonsillectomy.

- Subjects must have either tracheotomy or be ineffectively treated with CPAP due to
noncompliance, discomfort, un-desirable side effects, persistent symptoms despite
compliance use, or refusal to use the device.

- Children and their parents must be willing to have stimulation hardware permanently
implanted, and be willing to participate in follow-up visits, postoperative
polysomnography, and questionnaire completion.

- Children's parents must complete a questionnaire confirming that their child is
capable of communicating feelings of pain or discomfort. They must also confirm they
are able to assess their child for adverse effects related to device implantation.

- Children and their parents must be proficient in English for this pilot study in order
to ensure full disclosure during the consent process, as well as have the ability to
communicate with all staff, at all times, regarding any questions about participation
or concerns about this device.

- In order to participate, subjects will require written consent from both parents. All
study subjects must provide written assent as well.

Exclusion Criteria:

- Subjects will be excluded if they meet the following criteria: BMI >95th percentile
for age, apnea hypopnea index (AHI) <10 or >50 on in-lab polysomnography (PSG),
central or mixed apneas accounting for >25% of the total AHI, any anatomic finding on
physical exam or drug induced sleep endoscopy (DISE) that would compromise the
performance of stimulation (e.g. concentric soft palate collapse), other medical
conditions resulting in medical instability (e.g. congestive heart failure, recent
open heart surgery, immunosuppression, or chronic lung disease or aspiration),
presence of another medical condition requiring future magnetic resonance imaging
(MRI), history of cholesteatoma, or patients with another implantable device which
could interact unintentionally with the Inspire system.

- Subjects in whom general anesthesia for a surgical procedure is contraindicated due to
other medical illnesses or conditions will be excluded.

- Subjects with a life expectancy < 12 months will be excluded.

- Subjects who are unable to communicate pain or discomfort to their caretaker/parent,
based on parental or investigator assessment, will be excluded.

- Subjects with a history of bleeding or clotting disorders and those on blood thinning
or NSAID medications will be excluded from participation.

- Subjects taking muscle relaxant medication will be excluded from participation.

- Female subjects who are pregnant or plan to become pregnant during the study period
will be excluded. All female subjects will undergo urine beta-HCG testing on the day
of procedures requiring general anesthesia (DISE, implantation, and any other
unanticipated surgical procedures related to implantation). Subjects who are positive
will not undergo surgical implantation or procedures under general anesthesia.

- Subjects deemed unfit for participation by investigators or any other reason will be
excluded.