Clinical trial NCT03160456: Domiciliary Transcutaneous Electrical Stimulation in Obstructive Sleep Apnoea
Official title: Randomised Controlled Trial of Domiciliary Transcutaneous Electrical Stimulation in Obstructive Sleep Apnoea
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Obstructive Sleep Apnea
Keywords: upper airway
genioglossus
CPAP
electrical stimulation
sleep
sleep disordered breathing
Lead sponsor: Guy's and St Thomas' NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: King's College London
name: Royal Brompton & Harefield NHS Foundation Trust
name: King's College Hospital NHS Trust
First posted: 2017-05-19
Enrollment: 56
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised parallel group controlled clinical trial
Primary purpose: TREATMENT

Brief summary: The aim of this study is to assess the efficacy of transcutaneous electrical stimulation of the pharyngeal dilator muscles in patients with obstructive sleep apnoea in the community compared to usual care, and follow the patients for three months, as well as to assess compliance of non-invasive electrical stimulation of the upper airway dilator muscles in obstructive sleep apnoea patients over time and evaluate the control of symptoms and improvement in quality of life.

Detailed description: Obstructive sleep apnoea is highly prevalent, with the obesity epidemic increasing the problem. The best treatment for uncomplicated and moderate-severe OSA remains CPAP therapy. However, long-term adherence to treatment with CPAP is poor and there are few alternatives. Electrical stimulation of the dilator muscles of the upper airway has been shown to reduce nocturnal apnoeas significantly using an invasive approach, hypoglossal nerve stimulation, as well as by non-invasive transcutaneous stimulation. Although non-invasive transcutaneous stimulation may not be as effective as CPAP therapy in many OSA patients it could be an important option to treat some of the large number of patients who fail CPAP and might also be of use in those whose OSA is not judged sufficiently severe to warrant CPAP.

The investigators propose a study to use a transcutaneous electrical stimulation device in selected patients with OSA who do not tolerate CPAP therapy following assessment of the upper airway. Participants will undergo a baseline sleep study (polysomnography/home-based respiratory polygraphy). Following minimisation for gender (male/female) and OSA severity (mild/moderate-severe) they will be randomised into active treatment arm (transcutaneous electrical stimulation) or usual care (ongoing CPAP therapy). Patients will be treated over a period of 3-months in the community, re-assessed (including polysomnography/home-based respiratory polygraphy) and the results will be compared against usual care, ongoing CPAP therapy. This study will help to prepare a definitive multi-centre randomized controlled trial using the non-invasive method of upper airway stimulation in OSA.

The primary aim of this study is to assess efficacy and generate an accurate sample size estimation, test the subjective willingness of patients to use and objectively determined compliance with the treatment over a long period, as well as to specify the drop-out rate. The improvement in sleep apnoea will be the primary outcome measures. The symptomatic response, feasibility of the method, including compliance, comfort, adverse events, will be the secondary outcome measure. An ad-hoc analysis will be performed in the responder group (improvement in the apnoea-hypopnea index (AHI) by \>50% from baseline OR improvement in the 4% oxygen-desaturation index (ODI) \>25% from baseline OR AHI/4%ODI \<5/hour at follow up).

Eligibility criteria: Inclusion Criteria:

* mild-moderate OSA (AHI 5-35/hour)
* difficulties with or failed CPAP and/or withdrawn from standard care (CPAP \<4hours/night)
* Body mass index (BMI) 18.5-32 kg/m2
* No significant anatomical obstruction in the upper airway (e.g. normal sized tonsils).

Exclusion Criteria:

* No OSA (AHI \<5/h)
* Severe obstructive sleep apnoea (AHI\>35/hour)
* Exclusively postural sleep apnoea
* isolated Rapid-Eye-Movement (REM) sleep associated OSA
* Cachexia (BMI \<18.5 kg/m2)
* Obesity (BMI \>32 kg/m2)
* Hypercapnic respiratory failure (pCO2\>6.5 kPa)
* Features of obesity hypoventilation syndrome (elevated bicarbonate, HCO3- \>28mmol/L).
* enlarged tonsils (size 3-4)
* polyps and adenoids
* neuromuscular disease
* hypoglossal nerve palsy
* abnormal pulmonary function tests
* severe pulmonary hypertension
* valvular heart disease
* heart failure (New York Heart Association, NYHA III-IV)
* myocardial infarction and significant cardiac arrhythmias
* uncontrolled hypertension
* active psychiatric disease
* co-existing non-respiratory sleep disorder
* significant metal implants or cardiac/other pacemakers.
* facial hair that affects the correct placement of the hydrogel patch
* endoscopically identified contraindication to upper airway stimulation (multi-level obstruction)

These criteria are consistent with our experience from previous trials using transcutaneous electrical stimulation in OSA and likely to identify potential responders; these criteria are also similar to those from trials using hypoglossal nerve stimulation.

Primary outcomes:
measure: Apnoea Hypopnoea Index
timeFrame: 3 months
Secondary outcomes:
measure: Epworth Sleepiness Scale
timeFrame: 3 months
measure: Oxygen Desaturation Index
timeFrame: 3 months
measure: Usage of treatment
timeFrame: 3 months
measure: Compliance with treatment
timeFrame: 3 months
measure: Acceptance of device
timeFrame: 3 months
measure: Sleep related quality of life
timeFrame: 3 months
measure: Snoring
timeFrame: 3 months
measure: Genioglossus contraction
timeFrame: 3 months
measure: General quality of life
timeFrame: 3 months
measure: Anatomy of upper airway
timeFrame: at baseline
Other outcomes:
measure: Responder rate
timeFrame: 3 months
Locations:
city: London
country: United Kingdom
facility: Guy's & St Thomas' NHS Foundation Trust
Study officials:
affiliation: Guy's and St Thomas' NHS Foundation Trust
name: Joerg Steier, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College London
name: John Moxham, MD
role: STUDY_CHAIR
affiliation: Royal Brompton & Harefield NHS Foundation Trust
name: Michael I Polkey, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: King's College London NHS Foundation Trust
name: Kai Lee, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Pengo MF, Steier J. Emerging technology: electrical stimulation in obstructive sleep apnoea. J Thorac Dis. 2015 Aug;7(8):1286-97. doi: 10.3978/j.issn.2072-1439.2014.04.04.
citation: Bisogni V, Pengo MF, De Vito A, Maiolino G, Rossi GP, Moxham J, Steier J. Electrical stimulation for the treatment of obstructive sleep apnoea: a review of the evidence. Expert Rev Respir Med. 2017 Sep;11(9):711-720. doi: 10.1080/17476348.2017.1358619. Epub 2017 Jul 27.
citation: Pengo MF, Xiao S, Ratneswaran C, Reed K, Shah N, Chen T, Douiri A, Hart N, Luo Y, Rafferty GF, Rossi GP, Williams A, Polkey MI, Moxham J, Steier J. Randomised sham-controlled trial of transcutaneous electrical stimulation in obstructive sleep apnoea. Thorax. 2016 Oct;71(10):923-31. doi: 10.1136/thoraxjnl-2016-208691. Epub 2016 Jul 19.
citation: Campbell T, Pengo MF, Steier J. Patients' preference of established and emerging treatment options for obstructive sleep apnoea. J Thorac Dis. 2015 May;7(5):938-42. doi: 10.3978/j.issn.2072-1439.2015.04.53.
citation: Steier J, Seymour J, Rafferty GF, Jolley CJ, Solomon E, Luo Y, Man WD, Polkey MI, Moxham J. Continuous transcutaneous submental electrical stimulation in obstructive sleep apnea: a feasibility study. Chest. 2011 Oct;140(4):998-1007. doi: 10.1378/chest.10-2614. Epub 2011 Mar 31.