Diaphragm Pacing in motor neurone disease/ Amyotrophic Lateral Sclerosis

• Register: ISRCTN
• Last refreshed on: 17 October 2016
• Main ID: ISRCTN53817913
• Date of registration: 31/05/2011
• Prospective Registration: Yes
• Primary sponsor: Sheffield Teaching Hospitals NHS Foundation Trust (UK)
• Public title: Diaphragm Pacing in motor neurone disease/ Amyotrophic Lateral Sclerosis
• Scientific title: A randomised controlled trial evaluating NeuRx/4 Diaphragm Pacing (DP) in patients with muscle weakness due to motor neurone disease/Amyotrophic Lateral Sclerosis
• Date of first enrolment: 04/07/2011
• Target sample size: 108
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN53817913
• Study type: Interventional
• Study design: Multicentre randomised controlled trial (Treatment)

Countries of recruitment

United Kingdom

Contacts

• Name: Christopher McDermott

Key inclusion & exclusion criteria

Inclusion criteria: 1. Age 18 or older
2. Familial or sporadic MND/ALS diagnosed as laboratory-supported probable, probable, or definite according to the World Federation of Neurology El Escorial criteria
3. Stabilised on Riluzole therapy
4. Respiratory insufficiency as determined by one or more of:
4.1. Forced Vital Capacity (FVC) less than 75% predicted/Sniff Nasal Inspiratory Pressure (SNIP) less than 40 cmH2O
4.2. Supine vital capacity (VC) less than 75% of sitting or standing VC
4.3. Partial pressure of carbon dioxide in the blood (PaCO2) > 6kPa (daytime)
4.4. Significant overnight oxygen (O2) desaturation (>5% of night with Sp02 <90% during overnight oximetery)
5. Bilateral phrenic nerve function clinically acceptable as demonstrated by bilateral diaphragm movement with diaphragm ultrasound or X-ray fluoroscopy
6. Forced Vital Capacity (FVC) > 50% predicted or sniff nasal inspiratory pressure (SNIP) > 30 cmH2O in patients unable to perform FVC (bulbar patients)
Exclusion criteria: 1. Prior NIV prescription
2. Pre-existing implanted electrical device such as pacemaker or cardiac defibrillator
3. Underlying cardiac, pulmonary diseases or other disorders that would affect pulmonary tests independently of MND/ALS or would increase the risk of general anaesthesia
4. Current pregnancy or breastfeeding
5. Significant decision making incapacity preventing informed consent by the subject due to a major mental disorder such as major depression or schizophrenia or dementia
6. Marked obesity affecting surgical access to diaphragm or significant scoliosis/ chest wall deformity
7. The involvement in any respiratory trial that can influence the safety or outcome measures of this study within three months of the planned implantation of the device or during the year of follow up
8. Pre-existing diaphragm abnormality such as a hiatus hernia or paraoesophageal hernia of abdominal contents ascending into the thoracic cavity

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Motor neurone disease
Nervous System Diseases
Motor neuron disease

Intervention(s)

54 participants to be recruited to each of the 2 arms.

Arm 1 = Standard care alone (NIV), Arm 2 = Standard care (NIV) plus DP

NIV arm patients will attend clinic for initiation of NIV with a possible overnight stay. Baseline NIV settings, NIV prescription given, type of interface, humidification and type of machine will be recorded. The patient will take home a Patient Diary and be asked to record the amount of NIV used.

In the DP arm participants will be admitted to hospital for insertion of the DP device. A pre-operative safety check will occur either during the admission or in the week leading up to surgery. During the implantation procedure, incisions of 0.5 to 1 inch long will be made in the abdomen. More than one incision will be made so instruments can be passed through the abdominal wall as per standard laparoscopic procedure. The surgeon will identify the best location to place the electrodes within the diaphragm. A probe will be used to temporarily place an electrode on the surface of the diaphragm and to stimulate the diaphragm muscle at several locations to find the best location. Two electrodes will then be placed in each side of the diaphragm muscle. The lead wires from these electrodes will travel under the skin to the abdominal wall. The wires will be trimmed so that the ends sticking out of the skin are only 2 - 6 inches in length. An X-ray will be taken following the surgery to check the position of the wires and to make sure no air has travelled above the diaphragm and into the chest. If the damage to the nerve supply to the diaphragm is too great it is possible that the diaphragm will not be able to be stimulated with the electrodes and diaphragm pacing system. The scan/x-ray of the diaphragm performed during screening are an attempt to assess whether the diaphragm is stimulatable. However it is only possible to know for sure during the operation. If during the operation it is clear that the diaphragm is not stimulatable then the operatio

Primary Outcome(s)

The primary objective of this trial will be to evaluate the effect of Diaphragm Pacing (DP) on survival over the study duration in patients with MND/ amyotrophic lateral sclerosis (ALS) with respiratory muscle weakness.

Secondary Outcome(s)

To evaluate the effect of DP on:

Efficacy endpoints
1. Quality adjusted life years (QALYs) as calculated by combining EQ-5D and mortality data
2. Quality of life: sleep apnoea quality of life index (SAQLI), and SF-36
3. Quality of life of the main carer of the patient (Caregiver Burden Inventory)

For each efficacy endpoint, the treatment effect will be assessed by analysing the difference between groups over the 12-month follow-up period, and the difference at 12 months.

Safety endpoints
Safety (adverse events) and tolerability (patient withdrawal from treatment)

Secondary ID(s)

HTA 09/55/33, DiPALS , Protocol v1

Source(s) of Monetary Support

Health Technology Assessment Programme, Motor Neurone Disease Association (MNDA) (UK)