Condition category
Nervous System Diseases
Date applied
08/03/2010
Date assigned
18/03/2010
Last edited
26/05/2016
Prospective/Retrospective
Prospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
Obstructive Sleep Apnoea Hypopnoea (OSAH) involves repetitive narrowing or closure of the upper airway during sleep, which results in reduced breathing (hypopnoea) or paused breathing (apnoea). This abnormal breathing causes oxygen levels to drop and leads to wakening from sleep. Sleep disturbance results in excessive daytime sleepiness, poor concentration, personality changes and irritability. In the long term there is an increased risk of heart disease and stroke in affected individuals. OSAH is a chronic condition that generally requires life-long treatment. Patients with mild OSAH are often treated conservatively with advice on weight loss, alcohol consumption and sleeping position. The standard treatment for people with moderate to severe OSAH is Continuous Positive Airway Pressure (CPAP) where air is blown into the upper airway during sleep, via either a nasal or face mask, to prevent it collapsing. However, some patients are unable to tolerate this treatment. Mild to moderate OSAH can be treated with Mandibular Advancement Devices (MAD) which hold the lower jaw and tongue forward, making more space to breathe. Research evidence indicates that CPAP is more effective than MAD and MAD is better than sham (pretend) MAD for the treatment of OSAH. Two important research questions are not answered: is MAD more effective than no treatment, and is MAD effectiveness related to device complexity? The first question is important because patients using sham MAD are likely to experience discomfort and side effects but no benefit from the sham device. This can make MAD appear more effective than it actually is. Comparing MAD to no treatment is important to ensure the benefits of MAD are not overestimated. The second question is important as there is a wide range of MADs available and it is not known which type is the most effective. The aim of this study is to evaluate the clinical effectiveness and costs in a 'real life' setting where participants may not necessarily follow the prescribed MAD treatment due to inconvenience, discomfort and other side effects.

Who can participate?
Patients aged over 18 with mild to moderate OSAH

What does the study involve?
This study compares three types of MAD:
1. Bespoke: custom made, professionally fitted
2. Semi-bespoke: commercially available postal kit where self-fit MADs are formed from a dental impression mould used by the patient
3. Over the counter: commercially available off the shelf kit where the patient 'boils and bites' thermoplastic MAD
All participants receive four treatments (bespoke, semi-bespoke, over the counter, no treatment) for a period of 6 weeks each, in a random order. The first two weeks of this are an 'acclimatisation phase' where the patient is given the opportunity to get used to the device, followed by a 4 week 'treatment phase' where we assess how well the treatment is working. Between each treatment period there is a 1 week 'wash out' interval to ensure that any effects of the last treatment have worn off before starting a new treatment. We measure how often the patients’ breathing is paused or reduced during sleep using a home portable measurement device in the final week of each treatment period. We also measure quality of life, patient symptoms and daily functioning at the end of each treatment period. Side effects experienced using each device, cost of treatment, number of withdrawals from the study and patient preference are also measured. Participants choose which device they prefer at the end of the study.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
Papworth Hospital (UK)

When is the study starting and how long is it expected to run for?
September 2010 to June 2012

Who is funding the study?
NIHR Health Technology Assessment Programme - HTA (UK)

Who is the main contact?
Dr Tim Quinnell

Trial website

Contact information

Type

Scientific

Primary contact

Dr Tim Quinnell

ORCID ID

Contact details

Respiratory Support & Sleep Centre
Papworth Hospital
Papworth Everard
Cambridge
CB23 3RE
United Kingdom

Additional identifiers

EudraCT number

ClinicalTrials.gov number

Protocol/serial number

HTA 08/110/03; P01415

Study information

Scientific title

Crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea

Acronym

TOMADO

Study hypothesis

1. Are mandibular advancement devices (MADs) more effective than no treatment?
2. Does the level of MAD sophistication - bespoke, semi-bespoke and over the counter (OTC), representing a spectrum of complexity and cost - influence treatment outcome?

More details can be found at: http://www.nets.nihr.ac.uk/projects/hta/0811003
Protocol can be found at: http://www.nets.nihr.ac.uk/__data/assets/pdf_file/0008/51992/PRO-08-110-03.pdf

Ethics approval

Cambridgeshire 2 Research Ethics Committee, 14/01/2010, ref: 10/H0308/4

Study design

Single-centre four-arm four-period crossover randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised cross over trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Obstructive sleep apnoea

Intervention

The study will compare the clinical effectiveness and costs of three types of MAD (bespoke, semi-bespoke and over the counter) and a no treatment control for participants with mild to moderate OSAH. Each 6-week period (4-week for no treatment arm) will comprise of a 2-week acclimatisation phase, followed by a 4-week treatment phase. A 1-week washout period will follow active treatments.

Intervention type

Device

Phase

Not Specified

Drug names

Primary outcome measures

Apnoea-Hypopnoea Index (AHI). AHI is the frequency of apnoeas and hypopneas per hour of study.

Measured at baseline and then in the final week of each treatment period (5 times in total). The sleep diary will be completed daily during the treatment periods.

Secondary outcome measures

1. Epworth Sleepiness Scale (ESS)
2. Physiological indices from the respiratory polysomngraphy (PSG) - 4% Oxygen Desaturation Index, mean, minimum and time less than 90% of nocturnal SpO2
3. Blood pressure
4. Functional status (Functional Outcome of Sleep Questionnaire [FOSQ])
5. Generic (36-item short form health survey [SF-36]) and disease specific (Calgary Sleep Apnoea Quality of Life Index [SAQLI]) health related quality of life (HRQoL)
6. EuroQol EQ-5D transformed to the utility scale
7. Daily sleep diary (assessing adherence, hours use and retention)
8. Snoring scale (partner rated visual analogue scale)
9. Side effects, withdrawals and participant satisfaction and preference

Measured at baseline and then in the final week of each treatment period (5 times in total). The sleep diary will be completed daily during the treatment periods.

Overall trial start date

01/09/2010

Overall trial end date

01/06/2012

Reason abandoned

Eligibility

Participant inclusion criteria

1. Aged greater than or equal to 18 years, either sex
2. Obstructive sleep apnoea-hypopnoea confirmed by respiratory polysomnogram with apnoea-hypopnoea index (AHI) 5 to 30/hours
3. Excessive daytime sleepiness (ESS) greater than or equal to 11 and/or participant reported sleepiness
4. Sufficient teeth to allow satisfactory device retention
5. Ability to give written informed consent

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

90

Participant exclusion criteria

1. Primary central sleep apnoea
2. Coexistent sleep disorder or drug treatment considered likely to have significant impact on symptoms (especially sleepiness) or MAD effectiveness
3. Severe and/or unstable cardiovascular disease judged by clinician to warrant immediate continuous positive airway pressure (CPAP)
4. Other medical or psychiatric disorder judged likely to adversely interact with MAD or confound interpretation of its effectiveness
5. Significant periodontal disease or tooth decay; partial or complete edentulism; presence of fixed orthodontic devices
6. Temporomandibular joint pain or disease
7. Severe bruxism
8. Restriction in mouth opening or advancement of mandible
9. Respiratory failure
10. Inability to give informed consent or comply with the protocol
11. Pregnant women
12. Any other significant clinical contra-indication, e.g. disabling sleepiness upgrading the obstructive sleep apnoea-hypopnoea (OSAH) to severe

Recruitment start date

01/09/2010

Recruitment end date

01/06/2012

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Papworth Hospital
Cambridge
CB23 3RE
United Kingdom

Sponsor information

Organisation

Papworth Hospital NHS Foundation Trust (UK)

Sponsor details

Papworth Everard
Cambridge
CB23 3RE
United Kingdom

Sponsor type

Government

Website

http://www.papworthhospital.nhs.uk/index.php

Funders

Funder type

Government

Funder name

Health Technology Assessment Programme

Alternative name(s)

NIHR Health Technology Assessment Programme, HTA

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25035126
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/25359435

Publication citations

  1. Results

    Quinnell TG, Bennett M, Jordan J, Clutterbuck-James AL, Davies MG, Smith IE, Oscroft N, Pittman MA, Cameron M, Chadwick R, Morrell MJ, Glover MJ, Fox-Rushby JA, Sharples LD, A crossover randomised controlled trial of oral mandibular advancement devices for obstructive sleep apnoea-hypopnoea (TOMADO)., Thorax, 2014, 69, 10, 938-945, doi: 10.1136/thoraxjnl-2014-205464.

  2. Results

    Sharples L, Glover M, Clutterbuck-James A, Bennett M, Jordan J, Chadwick R, Pittman M, East C, Cameron M, Davies M, Oscroft N, Smith I, Morrell M, Fox-Rushby J, Quinnell T, Clinical effectiveness and cost-effectiveness results from the randomised controlled Trial of Oral Mandibular Advancement Devices for Obstructive sleep apnoea-hypopnoea (TOMADO) and long-term economic analysis of oral devices and continuous positive airway pressure., Health Technol Assess, 2014, 18, 67, 1-296, doi: 10.3310/hta18670.

Additional files

Editorial Notes

26/05/2016: Plain English summary added.