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

Primary Purpose

Sleep Apnea, Obstructive, Down Syndrome

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Inspire® Upper Airway Simulation System (Model 3028 IPG )

About this trial

This is an interventional treatment trial for Sleep Apnea, Obstructive

Eligibility Criteria

10 Years - 21 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Children's Healthcare of Atlanta - Egleston Hospital
Massachusetts Eye and Ear
Cincinnati Children's Hospital
Children's Hospital of Pittsburgh
Children's Hospital of The King's Daughters

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Inspire® Upper Airway Simulation System

Arm Description

Subjects meeting inclusion criteria, including sleep study and drug induced sleep endoscopy criteria, will undergo surgical placement of a hypoglossal nerve simulator (Inspire® Upper Airway Simulation System Model 3028 IPG). The simulator will be activated one month after surgery and subjects will undergo repeat sleep study evaluation and device titration at one, two, six and twelve months after implantation. Subjects will be followed for one year to determine safety and efficacy of the device.

Outcomes

Primary Outcome Measures

Serious Adverse Events

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

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 (UADE)

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.

Secondary Outcome Measures

Apnea-hypopnea Index (AHI)

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.

Obstructive Apnea-hypopnea Index

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.

Central Apnea Index

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.

Hypopnea Percentage

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.

Oxygenation Percentage of Time SpO2 < 90%

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.

Percentage of Time ETCO2 > 50 mmHg

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.

SpO2 Nadir

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

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

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.

Arousal Index

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.

OSA-18 Total Survey Score

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.

OSA-18 Overall Quality of Life Score

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.

Epworth Sleepiness Scale (ESS) Survey Score

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.

Full Information

NCT ID

NCT02344108

First Posted

January 13, 2015

Last Updated

April 10, 2022

Sponsor

Christopher Hartnick, M.D.

Collaborators

Emory University, Children's Hospital Medical Center, Cincinnati, Inspire Medical Systems, Inc., University of Pittsburgh, Children's Hospital of The King's Daughters

1. Study Identification

Unique Protocol Identification Number

NCT02344108

Brief Title

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

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Completed

Study Start Date

February 2015 (Actual)

Primary Completion Date

July 23, 2021 (Actual)

Study Completion Date

September 2, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Christopher Hartnick, M.D.

Collaborators

Emory University, Children's Hospital Medical Center, Cincinnati, Inspire Medical Systems, Inc., University of Pittsburgh, Children's Hospital of The King's Daughters

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Yes

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Sleep Apnea, Obstructive, Down Syndrome

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

42 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Inspire® Upper Airway Simulation System

Arm Type

Experimental

Arm Description

Intervention Type

Device

Intervention Name(s)

Inspire® Upper Airway Simulation System (Model 3028 IPG )

Other Intervention Name(s)

hypoglossal nerve stimulator

Intervention Description

Subjects will be implanted with a hypoglossal nerve stimulator. Safety and efficacy of implantation will be evaluated.

Primary Outcome Measure Information:

Title

Serious Adverse Events

Description

Time Frame

1 year

Title

Non-Serious Adverse Events

Description

Time Frame

1 year

Title

Unanticipated Adverse Device Effects (UADE)

Description

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.

Time Frame

1 year

Secondary Outcome Measure Information:

Title

Apnea-hypopnea Index (AHI)

Description

Time Frame

1 year

Title

Obstructive Apnea-hypopnea Index

Description

Time Frame

1 year

Title

Central Apnea Index

Description

Time Frame

1 year

Title

Hypopnea Percentage

Description

Time Frame

1 year

Title

Oxygenation Percentage of Time SpO2 < 90%

Description

Time Frame

1 year

Title

Percentage of Time ETCO2 > 50 mmHg

Description

Time Frame

1 year

Title

SpO2 Nadir

Description

Time Frame

1 year

Title

Sleep Efficiency

Description

Time Frame

1 year

Title

REM Percentage

Description

Time Frame

1 year

Title

Arousal Index

Description

Time Frame

1 year

Title

OSA-18 Total Survey Score

Description

Time Frame

1 year

Title

OSA-18 Overall Quality of Life Score

Description

Time Frame

1 year

Title

Epworth Sleepiness Scale (ESS) Survey Score

Description

Time Frame

1 year

10. Eligibility

Sex

All

Minimum Age & Unit of Time

10 Years

Maximum Age & Unit of Time

21 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Christopher J Hartnick, MD

Organizational Affiliation

Massachusetts Eye and Ear

Official's Role

Principal Investigator

Facility Information:

Facility Name

Children's Healthcare of Atlanta - Egleston Hospital

City

Atlanta

State/Province

Georgia

ZIP/Postal Code

30329

Country

United States

Facility Name

Massachusetts Eye and Ear

City

Boston

State/Province

Massachusetts

ZIP/Postal Code

02115

Country

United States

Facility Name

Cincinnati Children's Hospital

City

Cincinnati

State/Province

Ohio

ZIP/Postal Code

45229

Country

United States

Facility Name

Children's Hospital of Pittsburgh

City

Pittsburgh

State/Province

Pennsylvania

ZIP/Postal Code

15224

Country

United States

Facility Name

Children's Hospital of The King's Daughters

City

Norfolk

State/Province

Virginia

ZIP/Postal Code

23507

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

35446411

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.

Results Reference

derived

PubMed Identifier

34371294

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.

Results Reference

derived

PubMed Identifier

32271464

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.

Results Reference

derived

PubMed Identifier

31219619

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.

Results Reference

derived

PubMed Identifier

29098288

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.

Results Reference

derived

PubMed Identifier

27244805

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.

Results Reference

derived

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

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