Continuous Transcutaneous Electrical Stimulation in Sleep Apnoea

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01661712

Acronym

TESLA

Enrollment

Registered

2012-08-09

Start date

2013-03-31

Completion date

2015-12-31

Last updated

2018-12-06

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Obstructive Sleep Apnoea

Keywords

obstructive sleep apnoea,, continuous transcutaneous electrical stimulation

Brief summary

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

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.

Interventions

DEVICETranscutaneous electrical stimulation

Transcutaneous electrical stimulation (one night of electrical current titrated according to skin sensation)

DEVICESham stimulation

Sham stimulation for one night (no electrical stimulation)

Study design

Allocation

RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

DOUBLE (Subject, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

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).

Design outcomes

Primary

Measure	Time frame	Description
4% Oxygen Desaturation Index (ODI, 4%)	1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)	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.

Secondary

Measure	Time frame	Description
Apnoea-Hypopnoea Index (AHI)	1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)	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.
Nadir Oxygenation	1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)	The nadir oxygenation (lowest SpO2, %) during the sleep study is measured while the patients are asleep.
Patient Comfort	1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)	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.
Device Acceptance	1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)	Device acceptance during sleep study, as measured by a visual analogue scale (0-10points). Higher values in the scale range represent a better outcome.
Sleepiness	1st sleep study compared to 2nd sleep study (randomised order of intervention/sham or sham/intervention)	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.

Countries

United Kingdom

Participant flow

Recruitment details

This is a randomised, sham-controlled crossover trial using transcutaneous electrical stimulation of the upper airway dilator muscles in patients with confirmed obstructive sleep apnea (OSA).

Pre-assignment details

A total of 390 patients were assessed, 44 patients were screened. 8 patients were excluded as screening failures. 36 patients were randomised into the sequence 'Sham Stimulation, then True Stimulation' (n=18) or 'True Stimulation, then Sham Stimulation' (n-18). All 36 randomised subjects completed the trial, serving as their own control.

Participants by arm

Arm	Count
Sham Stimulation First, Then Transcutaneous Electrical Stimula The patient will undergo a sleep study and continuous transcutaneous electrical stimulation will be administered during the night. After 3 days of wash out the patient will undergo a sleep study with the sham intervention and no continuous transcutaneous electrical stimulation will be administered. An identical setup to the intervention will be used with the software indicating stimulation to keep staff blinded to the intervention. Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&Technology ltd., Petersfield, UK): The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external PC or laptop via a visual interface. It stimulates the pharyngeal dilator muscles in order to reduce sleep apnoea.	18
Transcutaneous Electrical Stimulation First, Then Sham Stimula The patient will undergo a sleep study with Sham stimulation. After 3 days of wash out the patient will will undergo a sleep study and continuous transcutaneous electrical stimulation will be administered during the night An identical setup to the intervention will be used with the software indicating stimulation to keep staff blinded to the intervention. Transcutaneous electrical stimulation (SOSATS device, MORGAN Innovation&Technology ltd., Petersfield, UK): The SOSATS unit is a first generation sleep apnoea research device which is programmed and controlled by an external PC or laptop via a visual interface. It stimulates the pharyngeal dilator muscles in order to reduce sleep apnoea.	18
Total	36

Baseline characteristics

Characteristic	Sham Stimulation First, Then Transcutaneous Electrical Stimula	Transcutaneous Electrical Stimulation First, Then Sham Stimula	Total
Age, Continuous	51.2 years STANDARD_DEVIATION 11.9	50.6 years STANDARD_DEVIATION 11	50.8 years STANDARD_DEVIATION 11.2
Sex: Female, Male Female	5 Participants	1 Participants	6 Participants
Sex: Female, Male Male	13 Participants	17 Participants	30 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	1 / 36	1 / 36
serious Total, serious adverse events	0 / 36	0 / 36

Outcome results

Primary

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.