DiPALS controlled trial

A randomised controlled trial evaluating NeuRx/4 Diaphragm Pacing in patients with respiratory muscle weakness due to Motor Neurone Disease.

DiPALS project logo

The context

ALS is a neurodegenerative disease resulting in death usually from respiratory failure within 2-3 years of symptom onset. Non-invasive ventilation (NIV) is a treatment, that when given to patients in respiratory failure, leads to improved survival and quality of life.

Diaphragm Pacing (DP) is a new technique which may offer additional or alternative benefits to patients with ALS, in respiratory failure.

We aimed to establish the safety and efficacy of diaphragm pacing with the NeuRx/4 DP system in patients with respiratory muscle weakness due to ALS.

What we did and what we found

We undertook a multicentre, open-label, randomised controlled trial at seven specialist ALS and respiratory centres in the UK.

Eligible participants had a diagnosis of ALS (ALS laboratory supported probable, clinically probable or clinically definite according to the World Federation of Neurology revised El Escorial criteria) who had been stabilised on riluzole for 30 days, were 18 years or older and were in respiratory failure.

The primary outcome was overall survival. A number of secondary clinical outcomes were measured to assess participant quality of life.

74 participants were randomised into the trial (and analysed): 37 participants to NIV plus pacing and 37 to standard care before the DMEC advised initially suspension of recruitment (December 2013), and subsequently discontinuation of pacing in all patients (June 2014), on safety grounds.

Follow up assessments continued until the planned end of the study in December 2014.

The median survival (inter-quartile range) was 22·5 (11·8; upper quartile not reached) months in the NIV arm; and was 11·0 (6·7 to 17·0) months in the NIV plus pacing arm, with an adjusted hazard ratio of 2·27 (95% CI 1·22 to 4·25; p=0·01).


This is the first randomised controlled trial of non-invasive ventilation alone versus non-invasive ventilation plus pacing.

Addition of diaphragm pacing to standard care with non-invasive ventilation was associated with decreased survival in patients with ALS.

Our results suggest that diaphragmatic pacing should not be used as a routine treatment for patients with ALS in respiratory failure.

Both the funder and sponsor agreed that given the substantial cost of the device and the apparent reduction in life years in the pacing arm the planned health economic analyses were unnecessary.

To date, we have fed back results to research participants on the trial and the MND community via the MND Association.

In addition to this, the Chief Investigator has attended several conferences to disseminate the findings of the research to MND Neurologists and Respiratory Clinicians both in the UK and worldwide.

Future plans

DPS should not be used as routine treatment in ALS patients experiencing respiratory insufficiency as it is associated with poor survival.

Results of the trial have been published in Lancet Neurology, Health Technology Assessment and actively disseminated at conferences.

NICE guidance IPG593 (Intramuscular diaphragm stimulation for ventilator-dependent chronic respiratory failure caused by motor neurone disease) have incorporated our findings.

Work is ongoing in ScHARR to review further impact of the Trial based on international use of DPS for MND.

Project staff

Name Site Telephone Number    E-mail
Dr Christopher McDermott
Chief Investigator
Sheffield Institute for Translational Neuroscience (SITraN) +44 (0)114 2222261 c.j.mcdermott@sheffield.ac.uk
Dr Cindy Cooper
Director, CTRU
ScHARR +44 (0)114 2220743 c.l.cooper@sheffield.ac.uk
Chin Maguire
Study Manager
ScHARR +44 (0)114 2220717 c.maguire@sheffield.ac.uk
Amanda Loban
Data Manager
ScHARR +44 (0)114 2220685 a.loban@sheffield.ac.uk
Mike Bradburn
ScHARR +44 (0)114 2220706 m.bradburn@sheffield.ac.uk
Simon Dixon
Health Economist
ScHARR +44 (0)114 2220724 s.dixon@sheffield.ac.uk
Heather Dakin
Trial Support Officer
ScHARR +44 (0)114 2226385   


Wendy Baird
Qualitative Methodology
ScHARR +44 (0)114 2220819



Site Study Members City Hospital Role
Christopher McDermott Sheffield Royal Hallamshire Hospital Chief Investigator /
Consultant Neurologist
Pamela Shaw Sheffield Royal Hallamshire Hospital Principal Investigator
Stephen Bianchi Sheffield Royal Hallamshire Hospital Respiratory Consultant
Roger Ackroyd Sheffield Northern General Hospital Surgeon
Andrew Bentley Manchester University Hospital of South Manchester Principal Investigator/
Respiratory Consultant
John Ealing Manchester Salford Royal Hospital Foundation Trust Consultant Neurologist
Simon Galloway Manchester University Hospital of South Manchester Surgeon
Katie McCalman Manchester University Hospital of South Manchester Research Nurse
Kevin Talbot Oxford John Radcliffe Hospital Principal Investigator /
Consultant Neurologist
John Stradling Oxford John Radcliffe Hospital Respiratory Consultant
Nick Maynard Oxford John Radcliffe Hospital Surgeon
Rachel Marsden Oxford John Radcliffe Hospital Research Nurse
Tim Williams Newcastle Royal Victoria Infirmary Principal Investigator /
Consultant Neurologist
Simon Baudouin Newcastle Royal Victoria Infirmary Respiratory Consultant
Dayalan Karat Newcastle Royal Victoria Infirmary Surgeon
Steve Dodds Newcastle Royal Victoria Infirmary Research Nurse
Philip Hughes Plymouth Derriford Hospital Principal Investigator/
Respiratory Consultant
Oliver Hanemann Plymouth Derriford Hospital Neurology Consultant
Richard Berresford Plymouth Derriford Hospital Surgeon
Mary Jo Trimmer Plymouth Derriford Hospital Research Nurse
Mark Elliott Leeds St James University Hospital Principal Investigator
Agam Jung Leeds St James University Hospital Consultant Neurologist
Abezar Sarela Leeds St James University Hospital Surgeon
Clair Favager Leeds St James University Hospital Research Nurse
Craig Armstrong Leeds St James University Hospital Research Nurse
Richard Orrell London Royal Free Hospital Principal Investigator
Christine Mickelson London Royal Free Hospital Consultant Respiratory Therapist
Zak Rahman London Royal Free Hospital Surgeon
Mark Baker London Royal Free Hospital Research Nurse

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