Clinical trial NCT02344108: A Pilot Study to Evaluate the Hypoglossal Nerve Stimulator in Adolescents With Down Syndrome and Obstructive Sleep Apnea
Official title: A Pilot Study to Evaluate the Safety and Efficacy of the Hypoglossal Nerve Stimulator in Adolescents and Young Adults With Down Syndrome and Obstructive Sleep Apnea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Sleep Apnea, Obstructive
Down Syndrome
Lead sponsor: Massachusetts Eye and Ear Infirmary
Sponsor class: OTHER
Collaborators: name: Emory University
name: Children's Hospital Medical Center, Cincinnati
name: Inspire Medical Systems, Inc.
name: University of Pittsburgh
name: Children's Hospital of The King's Daughters
First posted: 2015-01-22
Enrollment: 42
Sex: ALL
Minimum age (years): 10
Maximum age (years): 21
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Obstructive sleep apnea (OSA) affects up to 1% of the general pediatric population and is associated with adverse behavior and quality of life, as well as long term cardiopulmonary system complications. Trisomy 21 (Down Syndrome) is the most common chromosomal disorder, with a incidence of approximately 1 per 660-800 births. Patients with Down Syndrome have a higher incidence of OSA than the general pediatric population, with rates of 30-60%, resulting in increased morbidity and decreased quality of life for affected individuals. In children, adenotonsillectomy (T\&A) is often a contributing factor to OSA, and adenotonsillectomy is a first line treatment. Children with Down Syndrome often undergo T\&A for obstructive sleep apnea, however 30-50% will have persistent obstructive sleep patterns requiring continuous positive pressure airway support (CPAP) or tracheotomy. Persistent obstruction is attributed to anatomic and physiologic differences in this population, including reduced muscular tone, macroglossia, maxillary hypoplasia, and lingual tonsil hypertrophy. This pilot study is designed to determine if 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, which has already been approved for use in adults with OSA, can be safely implanted and used in adolescents and young adults with Down Syndrome.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serious Adverse Events
timeFrame: 1 year
measure: Non-Serious Adverse Events
timeFrame: 1 year
measure: Unanticipated Adverse Device Effects (UADE)
timeFrame: 1 year
Secondary outcomes:
measure: Apnea-hypopnea Index (AHI)
timeFrame: 1 year
measure: Obstructive Apnea-hypopnea Index
timeFrame: 1 year
measure: Central Apnea Index
timeFrame: 1 year
measure: Hypopnea Percentage
timeFrame: 1 year
measure: Oxygenation Percentage of Time SpO2 < 90%
timeFrame: 1 year
measure: Percentage of Time ETCO2 > 50 mmHg
timeFrame: 1 year
measure: SpO2 Nadir
timeFrame: 1 year
measure: Sleep Efficiency
timeFrame: 1 year
measure: REM Percentage
timeFrame: 1 year
measure: Arousal Index
timeFrame: 1 year
measure: OSA-18 Total Survey Score
timeFrame: 1 year
measure: OSA-18 Overall Quality of Life Score
timeFrame: 1 year
measure: Epworth Sleepiness Scale (ESS) Survey Score
timeFrame: 1 year
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Children's Healthcare of Atlanta - Egleston Hospital
state: Georgia
city: Boston
country: United States
facility: Massachusetts Eye and Ear
state: Massachusetts
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital
state: Ohio
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh
state: Pennsylvania
city: Norfolk
country: United States
facility: Children's Hospital of The King's Daughters
state: Virginia
Study officials:
affiliation: Massachusetts Eye and Ear
name: Christopher J Hartnick, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Yu PK, Stenerson M, Ishman SL, Shott SR, Raol N, Soose RJ, Tobey A, Baldassari C, Dedhia RC, Pulsifer MB, Grieco JA, Abbeduto LJ, Kinane TB, Keamy DG Jr, Skotko BG, Hartnick CJ. Evaluation of Upper Airway Stimulation for Adolescents With Down Syndrome and Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. 2022 Jun 1;148(6):522-528. doi: 10.1001/jamaoto.2022.0455.
citation: Stenerson ME, Yu PK, Kinane TB, Skotko BG, Hartnick CJ. Long-term stability of hypoglossal nerve stimulation for the treatment of obstructive sleep apnea in children with Down syndrome. Int J Pediatr Otorhinolaryngol. 2021 Oct;149:110868. doi: 10.1016/j.ijporl.2021.110868. Epub 2021 Aug 5.
citation: Jayawardena ADL, Randolph GW, Hartnick CJ. Pediatric Modifications to Hypoglossal Nerve Stimulation for Obstructive Sleep Apnea: How I Do It. Laryngoscope. 2021 Feb;131(2):423-424. doi: 10.1002/lary.28661. Epub 2020 Apr 9. No abstract available.
citation: Caloway CL, Diercks GR, Keamy D, de Guzman V, Soose R, Raol N, Shott SR, Ishman SL, Hartnick CJ. Update on hypoglossal nerve stimulation in children with down syndrome and obstructive sleep apnea. Laryngoscope. 2020 Apr;130(4):E263-E267. doi: 10.1002/lary.28138. Epub 2019 Jun 20.
citation: Diercks GR, Wentland C, Keamy D, Kinane TB, Skotko B, de Guzman V, Grealish E, Dobrowski J, Soose R, Hartnick CJ. Hypoglossal Nerve Stimulation in Adolescents With Down Syndrome and Obstructive Sleep Apnea. JAMA Otolaryngol Head Neck Surg. 2018 Jan 1;144(1):37-42. doi: 10.1001/jamaoto.2017.1871.
citation: Diercks GR, Keamy D, Kinane TB, Skotko B, Schwartz A, Grealish E, Dobrowski J, Soose R, Hartnick CJ. Hypoglossal Nerve Stimulator Implantation in an Adolescent With Down Syndrome and Sleep Apnea. Pediatrics. 2016 May;137(5):e20153663. doi: 10.1542/peds.2015-3663.