Continuous Transcutaneous Electrical Stimulation in Sleep Apnoea

Study Overview
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Brief Summary
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The aim of this randomized, double-blinded, sham-controlled cross-over trial is to demonstrate the effectiveness of continuous transcutaneous electrical stimulation of the pharyngeal dilator muscles to reduce sleep-disordered breathing.

Detailed Description
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Obstructive sleep apnoea is the most common problem of sleep-disordered breathing. It affects at least four percent of the male and two percent of the female adult population. It is associated with excessive daytime sleepiness, causing significant disturbance of daytime routines affecting work, social life and memory; untreated, it also causes a significant cardiovascular and metabolic risk. The best available treatment for obstructive sleep apnoea is continuous positive airway pressure (CPAP). However, not everyone eligible tolerates this treatment because it requires them to sleep with a nasal or full-face mask that is connected by a tube to a machine. Although CPAP is recommended by the National Institute for Health and Clinical Excellence (NICE) for moderate-severe sleep apnoea, approximately one third of sleep apnoea patients who should be on CPAP stop therapy within five years. Mild sleep apnoea is currently treated with mandibular advancement splints and generic sleep hygiene advice. Continuous transcutaneous electrical stimulation (CTES) of the submental region activates the muscles that dilate the upper airway. This is where airway obstruction occurs in sleep apnoea. It has been shown that CTES at night for short periods (10minutes) effectively stimulates the genioglossus muscle, the strongest pharyngeal dilator and reduces upper airway obstruction, work of breathing and neural respiratory drive in patients with sleep apnoea. The London Respiratory Muscle Groups, based within King's Health Partners and the Royal Brompton Hospital, has developed a CTES stimulator device. This device senses apnoeas and snoring and delivers CTES until normal ventilation has been restored. We propose to undertake a randomized, double-blinded, sham-controlled cross-over trial with sleep apnoea patients to evaluate the efficacy of this method. Patients will be randomly assigned to a night of CTES or sham-stimulation. The primary outcome measure is the number of oxygen desaturations per hour (ODI) caused by apnoeas and the secondary outcome measures are sleepiness, as measured by the Epworth sleepiness score, the apnoea-hypopnoea-index (AHI) and comfort, as assessed by a visual analogue score. The sample size Calculation using data from our own published pilot study revealed that this study would require 44 patients to be enroled. The mean study duration until all outcomes will be assessed for each patient will be four weeks. We plan to commence the study in winter 2012/13 for a period of two years, including analysis and publication, to be concluded in December 2014.

Official Title
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Randomised, Double-blinded, Sham-controlled Cross-over Trial of Continuous Transcutaneous Electrical Stimulation of the Pharyngeal Dilator Muscles in Obstructive Sleep Apnoea

Conditions
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Obstructive Sleep Apnoea

Intervention / Treatment
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* Device: Transcutaneous electrical stimulation
* Device: Sham stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: males and females, age >18years and <75years, body-mass index (BMI) >18 and <40kg/m2, non-smokers, sleep apnoea with an ODI ≥15/h or sleep apnoea with an ODI ≥5/h plus an Epworth sleepiness score >10. Exclusion Criteria: morbid obesity (BMI>40kg/m2) or cachexia (BMI<18kg/m2), obesity-hypoventilation syndrome (total sleep time with oxygen saturation (SpO2) less than 90% of more than 10% of the night), active smokers or smoking history of >20pack years, acute or critical illness, acute psychosis or chronic mental disorder affecting capacity, previous home-mechanical non-invasive ventilation and metal implants in the upper part of the body (this excludes dental implants).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Transcutaneous electrical stimulation<br>One night of transcutaneous electrical stimulation (electrical current titrated according to skin sensation) | Device: Transcutaneous electrical stimulation<br>* Transcutaneous electrical stimulation (one night of electrical current titrated according to skin sensation)<br>|
| Sham Comparator: Sham stimulation<br>One night of sham stimulation (no electrical current) | Device: Sham stimulation<br>* Sham stimulation for one night (no electrical stimulation)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 4% Oxygen Desaturation Index (ODI, 4%) | The primary outcome measure for this trial is the 4% oxygen desaturation index (ODI, 4%) per hour of sleep (h-1). The 4% ODI was chosen as primary outcome parameter over the AHI because an incomplete re-opening of the upper airway during an ongoing apnoeic effort caused by transcutaneous electrical stimulation (CTES) may result in a nominal increase of the AHI. We consider that the 4% ODI would be a more robust marker for the severity of sleep apnoea, low average oxygen levels indicating obesity-hypoventilation syndrome which will be an exclusion criterion. Although a specific cut off is not well defined a 4% ODI ≥5 represent mild OSA whilst a 4% ODI ≥15 represents moderate-severe OSA. Normal range is usually considered 0-5 events/hour. | 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Apnoea-Hypopnoea Index (AHI) | The Apnoea-Hypopnoea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. An apnea (pause in breathing) is defined by a temporary cessation of breathing that must last for at least 10 seconds and be associated with a decrease in blood oxygenation. A hypopnoea is a reduction of ventilation (shallow breathing) but not a complete cessation of breathing, lasting al least 10 seconds and associated with a decrease in blood oxygenation. | 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention) | 
| Nadir Oxygenation | The nadir oxygenation (lowest SpO2, %) during the sleep study is measured while the patients are asleep. | 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention) | 
| Patient Comfort | Patient comfort during the sleep study, as measured by a visual analogue scale (0-10 points). Higher values in the scale range represent a better outcome. | 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention) | 
| Device Acceptance | Device acceptance during sleep study, as measured by a visual analogue scale (0-10points). Higher values in the scale range represent a better outcome. | 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention) | 
| Sleepiness | Daytime sleepiness as an ad-hoc measurement, as measured by the Stanford Sleepiness Scale (0-7 points, x). Higher values in the scale range represent more severe sleepiness. | 1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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obstructive sleep apnoea,, continuous transcutaneous electrical stimulation