Domiciliary transcutaneous electrical stimulation in patients with obstructive sleep apnoea and limited adherence to continuous positive airway pressure therapy: a single-centre, open-label, randomised, controlled phase III trial.

Background: Hypoglossal nerve stimulation (HNS) for obstructive sleep apnoea (OSA) is a novel way to manage the condition. We hypothesised that in patients with OSA and limited adherence to continuous positive airway pressure (CPAP) therapy, domiciliary transcutaneous electrical stimulation (TESLA) would control sleep apnoea and provide health benefits. Methods: We undertook a single-centre, open-label, randomised, controlled phase III trial in patients with OSA (apnoea-hypopnoea-index [AHI] 5-35 h-1), a BMI of 18.5-32 kg∗m-2, and a documented lack of adherence to CPAP therapy (<4 h∗night-1) at Guy's & St Thomas' NHS Foundation Trust (hospital), UK. Patients were randomly assigned (1:1) using minimisation (gender and OSA severity) to receive TESLA or usual care (CPAP) for at least 3 months; sleep study analysis was provided without knowledge of the assignment arm. The primary outcome was change in AHI at 3-months. The primary outcome and safety were analysed in the intention-to-treat population. Data are reported as median (interquartile range), unless otherwise explained. This trial is registered at ClinicalTrials.gov, NCT03160456. Findings: Between 6 June 2018 and 7 February 2023, 56 participants were enrolled and randomly assigned (29 patients in the intervention group and 27 in the usual care group). Patients were followed up for a median of 3.0 months (IQR 3.0; 10.0). The groups were similar in terms of age (55.8 (48.2; 66.0) vs 59.3 (47.8; 64.4) years), gender (male:female, 19:10 vs 18:9) and BMI (28.7 (26.4; 31.9) vs 28.4 (24.4; 31.9) kg∗m-2). The unadjusted group difference in the ΔAHI was -11.5 (95% CI -20.7; -2.3) h-1 (p = 0.016). Adjusted for the baseline value, the difference was ΔAHI -7.0 (-15.7; 1.8) h-1 (p = 0.12), in favour of the intervention. Minor adverse events were found in one of the participants who developed mild headaches related to the intervention. Interpretation: Domiciliary TESLA can be used safely and effectively in OSA patients with poor adherence to CPAP, with favourable impact on sleepiness and sleep fragmentation. Despite pandemic-related limitations of the amended protocol this trial provides the evidence that TESLA improves clinically meaningful outcomes over the observed follow up period, and the transcutaneous approach is likely to offer an affordable alternative for responders to electrical stimulation in clinical practice. Funding: British Lung Foundation, United Kingdom Clinical Research Collaboration-registered King's Clinical Trials Unit at King's Health Partners.

Transcutaneous electrical stimulation in obstructive sleep apnoea: current developments and concepts of the TESLA-home programme.

PURPOSE OF REVIEW: Obstructive sleep apnoea (OSA) is a highly prevalent condition affecting about 1 billion people worldwide. The first line therapy for most patients with OSA is continuous positive airway pressure (CPAP) therapy. However, there are significant limitations with long-term adherence to CPAP therapy, which may be as low as 30-60%. RECENT FINDING: Electrical stimulation of the hypoglossal nerve has been studied in recent years. It achieves upper airway patency by causing a contraction of the genioglossus muscle, the strongest dilator of the upper airway, and by maintaining its neuromuscular tone in the asleep patient with OSA. Electrical stimulation can be delivered invasively, hypoglossal nerve stimulation (HNS), and noninvasively, transcutaneous electrical stimulation in OSA (TESLA). However, randomised controlled trials, the STAR and the TESLA trial, have provided promising results on efficacy and safety of the methods. SUMMARY: Patient and public involvement underlines the interest in TESLA and HNS and highlights the need to provide non-CPAP therapeutic options to those who may find it difficult to cope with first line therapies. The relatively low costs and the favourable safety profile of the TESLA approach provide the chance to offer this treatment to patients with OSA following further development of the evidence.

Electrical stimulation as a therapeutic approach in obstructive sleep apnea - a meta-analysis.

PURPOSE: Electrical stimulation of the upper airway dilator muscles is an emerging treatment for obstructive sleep apnea (OSA). Invasive hypoglossal nerve stimulation (HNS) has been accepted as treatment alternative to continuous positive airway pressure (CPAP) for selected patients, while transcutaneous electrical stimulation (TES) of the upper airway is being investigated as non-invasive alternative. METHODS: A meta-analysis (CRD42017074674) on the effects of both HNS and TES on the apnea-hypopnea index (AHI) and the Epworth Sleepiness Scale (ESS) in OSA was conducted including published evidence up to May 2018. Random-effects models were used. Heterogeneity and between-study variance were assessed by I2 and τ2, respectively. RESULTS: Of 41 identified clinical trials, 20 interventional trials (n = 895) could be pooled in a meta-analysis (15 HNS [n = 808], 5 TES [n = 87]). Middle-aged (mean ± SD 56.9 ± 5.5 years) and overweight (body mass index 29.1 ± 1.5 kg/m2) patients with severe OSA (AHI 37.5 ± 7.0/h) were followed-up for 6.9 ± 4.0 months (HNS) and 0.2 ± 0.4 months (TES), respectively. The AHI improved by - 24.9 h-1 [95%CI - 28.5, - 21.2] in HNS (χ2 79%, I2 82%) and by - 16.5 h-1 [95%CI - 25.1, - 7.8] in TES (χ2 7%, I2 43%; both p < 0.001). The ESS was reduced by - 5.0 (95%CI - 5.9, - 4.1) (p < 0.001). CONCLUSION: Both invasive and transcutaneous electrical stimulation reduce OSA severity by a clinically relevant margin. HNS results in a clinically relevant improvement of symptoms. While HNS represents an invasive treatment for selected patients with moderate to severe OSA, TES should be further investigated as potential non-invasive approach for OSA.

Ultrasound assessment of upper airway dilator muscle contraction during transcutaneous electrical stimulation in patients with obstructive sleep apnoea.

BACKGROUND: Electrical current can be used to stimulate upper airway dilator muscles to treat obstructive sleep apnoea (OSA). Ultrasound devices are widely available and may be used to detect contraction of the upper airway dilator muscles assessing the functionality of electrical stimulation (ES) used for this treatment. METHODS: In a physiological sub-study of a randomised controlled trial, patients with OSA underwent ultrasound examination to assess contraction of the upper airway dilator muscles in response to transcutaneous ES. Ultrasound scans were scored according to the picture quality (poor = '0', acceptable = '1' and good = '2'). Tongue base thickness was assessed in mid-sagittal and coronal planes with (D2, A2) and without ES (D1, A1), while awake and seated. The primary outcome was to determine the increase in tongue thickness during ES in both views (D2 - D1 = ΔD), as well as any increase in the cross-sectional area (CSA) in the coronal view (A2 - A1 = ΔA). Data were presented as mean and standard deviation (SD). RESULTS: Fourteen patients [eight male, age 57.5 (9.8) years, body mass index (BMI) 29.5 (2.8) kg/m2] with OSA [Apnea-Hypopnea Index (AHI) 19.5 (10.6) × hour-1] were studied. Quality of the ultrasound scans was acceptable or good with 1.5 (0.5) points. In the mid-sagittal plane, ΔD was +0.17 (0.07) cm in midline and +0.21 (0.09) cm in the widest diameter, a percentual change of 12.2% (4%) and 12.8% (5.2%) (P<0.001, respectively). In the coronal plane, ΔD was +0.17 (0.04) cm, an increase of 12.3% (4.6%) (P<0.001, respectively), ΔA in the CSA increased by +18.9% (3.0%) with stimulation (P<0.001). There was a negative correlation between age and ΔA (r= -0.6, P=0.03), but no significant associations were found with gender, BMI, neck circumference, Epworth Sleepiness Scale (ESS), AHI, skin and subcutaneous tissue in the submental area. CONCLUSIONS: Ultrasound can visualise upper airway dilator muscle contraction during transcutaneous ES in awake patients with OSA. Contraction is best detected in the CSA of the tongue base in the coronal plane.