Sleep Disorders: Upper-Airway Stimulation for Obstructive Sleep Apnea, Dyssomnias.

Upper-Airway Stimulation for Obstructive Sleep Apnea

BACKGROUND

Obstructive sleep apnea is associated with considerable health risks. Although continuous positive airway pressure (CPAP) can mitigate these risks, effectiveness can be reduced by inadequate adherence to treatment. We evaluated the clinical safety and effectiveness of upper-airway stimulation at 12 months for the treatment of moderate-to-severe obstructive sleep apnea.

METHODS

Using a multicenter, prospective, single-group, cohort design, we surgically implanted an upper-airway stimulation device in patients with obstructive sleep apnea who had difficulty either accepting or adhering to CPAP therapy. The primary outcome measures were the apnea–hypopnea index (AHI; the number of apnea or hypopnea events per hour, with a score of ?15 indicating moderate-to-severe apnea) and the oxygen desaturation index (ODI; the number of times per hour of sleep that the blood oxygen level drops by ?4 percentage points from baseline). Secondary outcome measures were the Epworth Sleepiness Scale, the Functional Outcomes of Sleep Questionnaire (FOSQ), and the percentage of sleep time with the oxygen saturation less than 90%. Consecutive participants with a response were included in a randomized, controlled therapy-withdrawal trial.

RESULTS

The study included 126 participants; 83% were men. The mean age was 54.5 years, and the mean body-mass index (the weight in kilograms divided by the square of the height in meters) was 28.4. The median AHI score at 12 months decreased 68%, from 29.3 events per hour to 9.0 events per hour (P<0.001); the ODI score decreased 70%, from 25.4 events per hour to 7.4 events per hour (P<0.001). Secondary outcome measures showed a reduction in the effects of sleep apnea and improved quality of life. In the randomized phase, the mean AHI score did not differ significantly from the 12-month score in the nonrandomized phase among the 23 participants in the therapy-maintenance group (8.9 and 7.2 events per hour, respectively); the AHI score was significantly higher (indicating more severe apnea) among the 23 participants in the therapy-withdrawal group (25.8 vs. 7.6 events per hour, P<0.001). The ODI results followed a similar pattern. The rate of procedure-related serious adverse events was less than 2%.

CONCLUSIONS

In this uncontrolled cohort study, upper-airway stimulation led to significant improvements in objective and subjective measurements of the severity of obstructive sleep apnea.

Purpose

The purpose of this clinical trial is to demonstrate long-term safety and efficacy of the Inspire system. The Inspire Upper Airway Stimulation (UAS) therapy is intended to treat moderate-to-severe obstructive sleep apnea by improving airway patency through stimulation of the hypoglossal nerve. Study objectives include demonstrating that the Inspire system improves key indices of sleep apnea in a pre-specified percentage of patients.

 

 

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Outcomes Assessor) Primary Purpose: Treatment
Official Title:	Effects of the Inspire Implantable Nerve Stimulation System on Obstructive Sleep Apnea

Primary Outcome Measures:

• Apnea Hypopnea Index [ Time Frame: Twelve months ] [ Designated as safety issue: No ]

Apnea hypopnea index with therapy at twelve months versus that pre-therapy

 

• Oxygen Desaturation Index [ Time Frame: Twelve months ] [ Designated as safety issue: No ]

Oxygen desaturation index with therapy at 12 months versus that pre-therapy

 

• Safety [ Time Frame: Twelve months ] [ Designated as safety issue: Yes ]

Description of all adverse events

 

Secondary Outcome Measures:

• Sleep related quality of life [ Time Frame: Twelve months ] [ Designated as safety issue: No ]

Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire values at twelve months versus those pre-therapy

 

• Long-term efficacy [ Time Frame: Long-term ] [ Designated as safety issue: No ]

Change in sleep study paramaters including when therapy is turned off

 

• Sleep Architecture Changes [ Time Frame: 12 months ] [ Designated as safety issue: No ]

Analysis of sleep architecture variables (e.g., SaO2) at the 12-month follow-up

 

 

Enrollment:	900
Study Start Date:	July 2010
Estimated Study Completion Date:	March 2014
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

The stimulator is surgically positioned subcutaneously near the clavicle in the upper chest, and connects to a stimulation lead (around a hypoglossal nerve) and a sensing lead (in the chest). The stimulation contracts a patient’s upper airway muscles to maintain airway patency, with the intent to keep the airway open during inspiration.

Detailed Description:

OSA is characterized by recurrent episodes of airflow obstruction in the upper airway that results in oxygen desaturations and arousals from sleep. The most common symptom of OSA is excessive daytime sleepiness. Recent studies have also shown clear association of OSA with the development of obesity, hypertension, diabetes mellitus, and congestive heart failure.

Of those who are treated with CPAP, less than half remain effectively treated due to poor compliance, ineffective patient selection or inadequate therapeutic effect. Surgical procedures of the upper airway such as uvulopalatopharyngoplasty (UPPP) or tongue-based procedures have also met with equivocal results. The upper airway stimulation (UAS) therapy being evaluated in this trial may be a better alternative for treating airway obstructions involving the base of the tongue.

All enrolled subjects will participate in pre-implant testing to verify eligibility for implant. Following pre-implant testing, qualified subjects will undergo a surgical procedure to implant the Inspire system. Following implant, subjects will have scheduled follow-up visits, with data through 12 months serving as the primary endpoint.

 

Keywords: Tongue, surgery, neurostimulation, hypoglossal nerve, upper airwaDyssomniasy stimulation, Apnea, Sleep Apnea Syndromes, Sleep Apnea, Obstructive, Respiration Disorders, Respiratory Tract Diseases, Signs and Symptoms, Respiratory  Signs and Symptoms, Sleep Disorders, Intrinsic, Dyssomnias, Sleep Disorders, Nervous System Diseases, Upper-Airway Stimulation for Obstructive Sleep Apnea

Dr.VL.