DENIM

Delivering Effective Non-Invasive Ventilation in Motor Neuron Disease (DENIM)

UK Chief Investigator

Dr Esther Hobson

Research summary

Motor neuron disease (MND) affects 1 in 300 people. There is no known cure. Most people die due to weakness of the muscles that control breathing. Non-invasive ventilation (NIV) is the only treatment shown to help people with MND live longer, feel better and enjoy life more. NIV involves wearing a mask over the face to support breathing and many people find it hard to use. More than half of people are not getting the full benefits, either because they are unable to use it for long enough or because it does not work well.

People with MND who are starting NIV will take part in the DENIM study. Each person will be involved for the first 12 weeks after starting NIV. All patients will receive the usual care from their healthcare team, but half will also receive additional support. The healthcare team will get extra training to help them understand MND and NIV better. In addition, extra information will be sent automatically from the NIV machine in the patient's home (called telemonitoring). This tells staff if there are problems with the NIV without patients having to remember. We want to find out if people using the intensive home support service are able to use their NIV for longer periods and get more benefit. We will also see if people live longer and feel better. We will make it as easy as possible to take part because people with MND are very unwell and staff are busy. We will collect most information from the NIV machines automatically. We will also use short questionnaires for patients twice and interview some patients and their carers. Staff will complete questionnaires, interviews and observations to learn if the programme works and consider how it can be rolled out widely in the NHS.

Current status

Open to recruitment

Recruitment target

252 participants

Click here to see how many patients have been recruited into this study to date (external link to the NIHR public study search) 

Recruitment groups

Patients with MND

Locations

• Leeds, Principal Investigator: Dr Dipansu Ghosh 

• Leicester, Principal Investigator: Dr Rahul

• London - The Royal London Hospital, Principal Investigator: Alex Long 

• London - St George's Hospital, Principal Investigator: Dr Nicola Walters 

• London - St Thomas' Hospital, Principal Investigator: Dr Georgios Kaltsakas 

• Newcastle, Principal Investigator: Dr Ben Messer 

• Norwich, Principal Investigator: Emma Larner 

• Nottingham, Principal Investigator: Dr Milind Sovani 

• Oxford, Principal Investigator: Dr Christopher Turnbull 

• Manchester, Principal Investigator: Dr Andras Bikov 

• Sheffield, Principal Investigator: Dr Esther Hobson

• Stoke, Principal Investigator: Dr Naveed Mustfa 

Contact details

Email: denimtrial@sheffield.ac.uk

Key dates

Recruitment opening date: 24 June 2025

Planned recruitment end date: 30 April 2027

Inclusion / exclusion criteria

Trial participant inclusion criteria:

1. Patients aged 18 years or over.

2. Have a diagnosis of MND confirmed by a consultant neurologist.

3. With a clinical diagnosis of respiratory insufficiency according to local protocols, published guidelines and/or specialist opinion.

4. Respiratory insufficiency judged by the treating clinician to be severe enough to warrant long term domiciliary NIV and requiring NIV optimisation within the duration of the study (12 weeks).

5. NIV initiated at home, in an outpatient setting or in hospital if hospital stay is less than or equal to 3 days post NIV initiation.

6. Able to provide informed consent. Adults agreeing to try NIV and able to provide assent (evidence of agreement to take part in the study) but unable to provide informed consent will be able to participate if a consultee (close relative, informal carer, immediate care team) provides a consultee declaration. 

Process evaluation patient interviews inclusion criteria:

1. Have consented to participate in DENIM.

2. Are in the intervention arm.

3. Are able and willing to participate in interviews (various options for facilitation available) and/or ethnographic observations.

4. If relevant, are willing to share their preferred language for participation with the research team, to allow an appropriate researcher to be identified.

Process evaluation family/carer inclusion criteria:

1. Relative/friend has consented to participate in DENIM.

2. Are able and willing to participate in interviews and/or ethnographic observations.

Process evaluation staff interview inclusion criteria:

1. Direct contact with at least one patient who is participating in DENIM.

2. Are able and willing to participate in interviews and/or ethnographic observations.

ACCESS sub study inclusion criteria:

1. From an ethnic minority and/or where the patient's main language is not English.

2. Or with low levels of digital health literacy (either those identified by the site teams  or those scoring < 7 on the 3-Item Measure of Digital Health Care Literacy at baseline).

3. Or women over 80 with bulbar onset disease.

Key exclusion criteria:

1. Already initiated on NIV/CPAP for MND or another reason.

2. Using tracheostomy ventilation.

3. No way to connect the ventilation software to the internet whilst in the community.

4. Patients not requiring optimisation within 12 weeks (e.g. those given the machine but are unable to commence NIV due to lack of social care).

Funder

National Institute for Health and Care Research (NIHR). Funder reference: NIHR158715

Sponsor

Sheffield Teaching Hospitals NHS Foundation Trust

Study design

Interventional; stepped wedge cluster randomised controlled trial

Intervention

• Intervention: A theory-based package of staff education, highly intensive support, monitoring and optimisation using telemonitoring during the first 12 weeks of NIV use

• Control: standard care

Outcome measures

Primary outcome measure

NIV usage (the number of days in which patients use NIV for >4hr/day during week 9-12), measured automatically by the ventilator machine:

1.1. NIV usage: NIV usage from ventilator machine (first 14 days, first 28 days)

1.2. Calculation of the number of days in which patients use NIV for >4hr/day 

Secondary outcome measures

1. NIV usage (first 14 days, first 28 days, weeks 9-12) measured by the ventilator machine

1.1. The average (mean) daily usage

1.2. The number of patients achieving >4hr/day for >70% of nights

2. Nocturnal respiratory insufficiency, measured by overnight oximetry, for a single night at week 12

3. Time spent with oxygen saturations <90%, measured by overnight oximetry, for a single night at week 12

4. Time spent in oxygen desaturation index (ODI) of 4%, measured by overnight oximetry, for a single night at week 12

5. Patient reported outcome measures: collected at baseline and week 12

5.1. Quality of life (McGill quality of life questionnaire, developed for patients with a life-limiting illness)

5.2. Dyspnoea-12 (measuring respiratory symptoms, sensitive to change)

5.3. S3NIV (measures respiratory symptoms, sleep quality, and NIV-related side effects)

6. Health and social care resource use questionnaire, including EQ5D, collected from participant at week 12

7. Survival, collected from medical records, follow-up minimum 12 weeks, maximum of 27 months (week 108)

Exploratory outcomes

8. Ventilator effectiveness, collected from data report from ventilator for the first 14 days, first 28 days, and weeks 9-12

8.1. Tidal volumes

8.2. Ventilator asynchronies

8.3. Apnoea hypopnoea index

8.4. Leak

9. Nocturnal evidence of REM-related desaturation through overnight oximetry, Week 12

9.1. Evidence of REM-related desaturation trace

Explanatory implementation outcomes

10. Assessment of changes in barriers and facilitators to implementation at site level, pre and post intervention (NOMAD survey given to healthcare professionals during the site control arm, week 4 after intervention switch and end of the trial)

11. Fidelity: Percentage completeness of the first consultant workbook (intervention arm), assessed throughout site intervention arm

12. Fidelity: Number of times remote monitoring was reviewed at the pre-specific times, assessed throughout site intervention arm

13. Fidelity: Number of times workbook was reviewed per participant, assessed throughout site intervention arm