Can the mandibular advancement devices used for sleep apnoea reduce night time reflux?
| ISRCTN | ISRCTN16013232 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN16013232 |
| IRAS number | 304665 |
| Secondary identifying numbers | CPMS 53478, NIHR202744, IRAS 304665 |
- Submission date
- 05/09/2022
- Registration date
- 13/10/2022
- Last edited
- 20/05/2025
- Recruitment status
- No longer recruiting
- Overall study status
- Ongoing
- Condition category
- Digestive System
Plain English summary of protocol
Background and study aims
This project tries to help with two serious problems that patients often suffer from at the same time: Obstructive Sleep Apnoea (OSA) where parts of the airway collapse during sleep and gastro-oesophageal reflux disease (GORD) where stomach acids backtracks into the mouth causing pain, chronic cough, sore throat and tooth erosion. OSA affects 24.5% of the population and 45% of these suffer from GORD. It is thought that blocking the airway increases pressure in the stomach, forcing acid into the mouth until the patient breathes again. Our PPI group have informed us that if you can manage the sleep apnoea, you can also reduce the stomach acid reflux. CPAP, the gold standard treatment for OSA has been shown to reduce night-time reflux but this has never been tested for Mandibular Advancement Devices, a not-as-effective therapy that is better tolerated by patients. MADs. As nobody has investigated this before, we need to assess practical things, like if a patient can wear reflux checking devices and sleep devices at the same time. We will see if there will be any problems experienced in the patient journey of the trial and sort through any problems that may come up when multiple teams need to work together.
Who can participate?
Patients with both OSA and reflux.
What does the study involve?
Participants will receive CPAP therapy or a MAD. We will check their reflux levels and sleep breathing at nighttime while they are wearing ther devices and compare them with their reflux levels at start of the trial. When we are confident that the trial design is good and patients are happy participating in it, we will apply for funding for a bigger trial to check if the MAD can reduce reflux, improve patient’s quality of life and if this will represent a cost saving to the NHS.
What are the possible benefits and risks of participating?
There is no direct, immediate benefit to you from taking part in this research study. However, you will receive your assessment and treatments over a shorter time period, be offered both types of treatment and have increased information about your sleep device and whether it also helps your reflux. You will also have helped the dental and medical profession gain a better understanding of how sleep treatments impact on gastric reflux.
We do not know how easy it will be for patients to manage the gastric reflux pH testing, the sleep study and wear their device to treat their sleep condition at the same time. It has been done before but the comfort of this for patients has not been reported on. We think it will be slightly harder for those in the CPAP group as the facemask and pH probe may put pressure on the skin at night-time. However, everything will be done to make it as comfortable as possible. There are no lasting side effects and everything we use is standard of care and safe.
Where is the study run from?
Guy's and St Thomas' NHS Foundation Trust (UK)
When is the study starting and how long is it expected to run for?
April 2022 to May 2026
Who is funding the study?
National Institute for Health and Care Research (NIHR) (UK).
Who is the main contact?
Dr Saoirse O’Toole, saoirse.otoole@kcl.ac.uk
Dr Gabriella Wojewodka, gabriella.wojewodka@kcl.ac.uk
Contact information
Principal Investigator
Centre for Clinical, Oral and Translational Sciences
Floor 17, Tower Wing, Guy's Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
 ORCID ID |
0000-0002-2144-1847 |
|---|---|
| Phone | +44 20 7188 7188 |
| saoirse.otoole@kcl.ac.uk |
Scientific
King's College London
Oral Clinical Research Unit
Faculty of Dentistry, Oral & Craniofacial Sciences (FoDOCS)
Floor 26 Tower Wing, Guys Hospital
Great Maze Pond
London
SE1 9RT
United Kingdom
| gabriella.wojewodka@kcl.ac.uk |
Study information
| Study design | Interventional randomized controlled trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | 42325 MAD Reflux PIS V2 16Aug2022.pdf |
| Scientific title | Can mandibular advancement device treatment for obstructive sleep apnoea reduce nocturnal gastro-oesophageal reflux: a feasibility study |
| Study acronym | MAD Reflux |
| Study objectives | There is a growing body of evidence that Continuous Positive Airway Pressure (CPAP) therapy, the gold standard therapy for obstructive sleep apnoea, can reduce levels of gastro-oesophageal disease by maintaining a patent airway, thus reducing intrathoracic pressure differentials. This study tests the hypothesis that mandibular advancement devices, which also maintain a patent airway, may also have a similar impact on intrathoracic pressure differentials and may improve reflux. In addition, the greater compliance observed with mandibular advancement devices may mean that reflux is suppressed for a greater proportion of the night. |
| Ethics approval(s) |
Approved 25/08/2022, East Midlands - Nottingham 2 Research Ethics Committee (Equinox House, City Link, Nottingham, NG2 4LA, United Kingdom; +44 20 71048016; nottingham2.rec@hra.nhs.uk), ref: 22/EM/0157 |
| Health condition(s) or problem(s) studied | Obstructive sleep apnoea and nocturnal gastro-oesophageal reflux |
| Intervention | Visit 1 (Screening Visit) Medical history will be updated, and a full intraoral soft tissue and hard tissue examination will be completed. Participants will complete a reflux symptom index (RSI) questionnaire, Epworth Sleepiness Scale (ESS) questionnaire, Leicester Cough Questionnaire and a quality of life questionnaire (EQ-5D-5L). Patients will initially attend our gastroenterology department in the afternoon of Visit 1 to have a 24-hour impedance catheter placed for reflux monitoring. Patients will then undergo reflux monitoring using Sandhill Scientific multichannel impedance pH catheters (ZANBG44) which are inserted trans-nasally after applying local anaesthesia (xylocaine). For the home sleep study, participants will be provided with a type 2 sleep study device, the WatchPAT 200 (WP200; Itamar Medical Ltd., Caesarea, Israel), and given comprehensive instructions on how to perform a home sleep study. After their overnight sleep study with reflux monitoring, they will return the following day to the gastroenterology department for removal of the impedance catheter and return of the WatchPAT. The gastroenterology data will be captured by ZepHrTM recording device and data will be analysed using the BioVIEW Analysis software (5.7.1.0). The polysomnography data will be analysed by a qualified sleep technician. Participants who meet the inclusion/exclusion criteria will be randomly allocated in a 1:1 ratio to either the CPAP (10) or the MAD (10). Visit 2 (Intervention) Following inclusion and randomisation, the intervention for participants will consist of either a mandibular advancement device (n=10, Somnomed Avant) with the dental sleep medicine department or continuous positive airway therapy (n=10) with the sleep medicine department. - Mandibular Advancement Device Group Intraoral digital impressions and a digital protrusive record will be taken using 3M true definition intraoral scanner (3M ESPE, UK). A mandibular advancement device (SomnoMed Avant, Somnomed UK) with a compliance chip for objective compliance monitoring will be constructed and fitted 3 weeks later. Following checks for fit, retention and comfort, the appliance will be titrated using subjective patient improvements in sleep and quality of life to gauge successful titration. - CPAP Therapy Group A CPAP mask will be fitted and patients will be issued with an autoset CPAP device (APAP, S8/S9, ResMed Ltd, Sydney, Australia) for home use. The patients will be instructed upon use. The patients in both groups will be given a period of three weeks to become accustomed to sleeping with the device. Visit 3 (Repeat pH impedance testing and questionnaires) Participants will repeat the RSI questionnaire, ESS questionnaire, Leicester Cough Questionnaire and QoL questionnaire. The pH impedance testing and Watch-PAT testing will be repeated as described above. Compliance levels for the MAD and CPAP therapy on the same night will be obtained. |
| Intervention type | Device |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | mandibular advancement device |
| Primary outcome measure | Current primary outcome measure as of 13/06/2023: 1. Percentage of approached patients who were screened for the trial measured using the percentage of patients eligible of those screened at Day 2 of the screening visit. 2. Percentage of eligible patients who were randomised measured using the percentage of screened patients who met the eligibility criteria versus those who were randomised at the randomisation timepoint. 3. Percentage of patients who completed the trial measured using number of patients who were randomised versus those who completed the trial at Day 2 of the final visit. _____ Previous primary outcome measure: 1. Patient screening to recruitment ratio 2. Patient willingness to be randomised and retention in the study 3. Acceptability of the trial and interventions in terms of the burden placed on patients such as, two impedance monitoring tests, following the same diet on the day of the test and ability to wear the Watch-PAT device and the CPAP or a MAD at the same time. |
| Secondary outcome measures | Current secondary outcome measures as of 13/06/2023: 1. Patient acceptability of the trial measured using qualitative interviews throughout the trial. 2. Hours that device is worn during sleep measured using the average number of hours worn per night as detected from the output from the therapeutic device throughout the trial period. 3. To assess the most sensitive quality of life questionnaire prior to the full trial by recording EQ-5D-5L, ICE-CAP A, and SWEMWBS at baseline and post intervention. 4. Rating of both therapies measured using a Visual Analog Scale (VAS) at Day 2 of final assessment visit (trial completion). 5. Number of potential participants identified by the care team with and without screening of referral letters measured using number of participants identified on clinics before the prescreening clinic and after the pre-screening. 6. Change in Reflux Symptom Index (RSI) using changes detected in the RSI validated questionnaire at baseline and post intervention. 7. Change in Epworth Sleepiness Scale (ESS) using changes detected in the ESS validated questionnaire at baseline and post intervention. 8. Change in cough using changes detected in the validated Leicester Cough Questionnaire at baseline and post intervention. 9. To identify and measure indicative costs and outcomes and select suitable economic outcomes measured by documenting health resource use including intervention costs, appointment times and attending health care practitioners throughout the trial. 10. To determine the acceptability of the intervention and economic data collection methods measured using qualitative questions at the qualitative interview (various timepoints). _____ Previous secondary outcome measures: 1. To determine an estimate of effect size of the clinical effectiveness of MADs and CPAP therapy at reducing nocturnal gastro-oesophageal reflux will be assessed. This will be done both while the device is in situ to determine the effect of the device and over the entire sleep duration to assess if the numbers of hours the therapy is used influences the overall clinical effectiveness. |
| Overall study start date | 01/04/2022 |
| Completion date | 31/05/2026 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Adult |
| Lower age limit | 18 Years |
| Sex | Both |
| Target number of participants | Planned Sample Size: 44; UK Sample Size: 44 |
| Key inclusion criteria | 1. Adult patients aged 18 years old and over 2. Confirmed OSA with Apnoea-Hypopnoea Index (AHI) score between 10 and 30 3. Confirmed gastro-oesophageal reflux disease with greater than 6 percent of acid exposure time < pH 4 over 24 hours 4. Patient will not have previously had CPAP or MAD therapy 5. Sufficient healthy teeth to support a mandibular advancement device (10 teeth in each jaw, no periodontal pockets > 5, no frank cavitation or loose crowns/bridges) 6. Willing and able to provide informed consent to the study |
| Key exclusion criteria | 1. Pregnancy or breast feeding 2. Unable or unwilling to stop GORD medication 2 days prior to assessment or unable to undergo manometry and pH impedence testing 3. Known liver disease or oesophageal/gastric varices 4. Previous surgery or intervention for reflux such as fundoplication 5. Any previous treatment for oesophageal neoplasia. 6. Unable/unwilling to tolerate either a CPAP mask or a mandibular advancement device 7. Medical history likely to impact on attendance or 24-hour impedance testing 8. Participation in other research within previous 30 days |
| Date of first enrolment | 20/02/2023 |
| Date of final enrolment | 31/12/2024 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centre
London
SE1 9RT
United Kingdom
Sponsor information
Hospital/treatment centre
R&D Department
16th Floor, Tower Wing
Great Maze Pond
London
SE1 9RT
England
United Kingdom
| Phone | +44 (0)20 71854426 |
|---|---|
| R&D@gstt.nhs.uk | |
| Website | http://www.guysandstthomas.nhs.uk/Home.aspx |
"ROR" |
https://ror.org/00j161312 |
Funders
Funder type
Government
No information available
Results and Publications
| Intention to publish date | 31/05/2026 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository, Available on request |
| Publication and dissemination plan | Planned publication in a high-impact peer-reviewed journal |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a publicly available repository (King’s Open Research Data System (KORDS) (https://kcl.figshare.com/browse), full anonymised dataset will be available for 5 years as of when the results have been published). Access to the data can be provided by contacting the study’s Chief Investigator. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | version 2 | 16/08/2022 | 13/10/2022 | No | Yes |
| Participant information sheet | version 2.0 | 08/03/2022 | 26/04/2023 | No | Yes |
| Protocol file | version 3.0 | 22/09/2022 | 13/06/2023 | No | No |
| HRA research summary | 28/06/2023 | No | No | ||
| Protocol article | 24/08/2023 | 25/08/2023 | Yes | No |
Additional files
Editorial Notes
20/05/2025: The overall end date was changed from 31/05/2025 to 31/05/2026.
03/04/2024: The following changes were made:
1. The overall study end date was changed from 30/11/2023 to 31/05/2025.
2. The recruitment end date was changed from 30/09/2023 to 31/12/2024.
3. The intention to publish date was changed from 30/11/2024 to 31/05/2026.
25/08/2023: Publication reference added.
13/06/2023: The following changes were made to the trial record:
1. Uploaded protocol (not peer-reviewed) as an additional file.
2. The acronym was added.
3. The primary outcome measure was changed.
4. The secondary outcome measures were changed.
26/04/2023: The following changes have been made:
1. The recruitment start date has been changed from 01/12/2022 to 20/03/2023.
2. A participant information sheet has been uploaded.
05/09/2022: Trial's existence confirmed by the National Institute for Health and Care Research (NIHR) (UK).
