Polysomnographic Titration of Non-invasive Ventilation in Motor Neurone Disease
- Conditions
- Motor Neuron Disease / Amyotrophic Lateral Sclerosis
- Interventions
- Other: Intervention polysomnographyOther: Sham polysomnography
- Registration Number
- NCT05136222
- Lead Sponsor
- University of Melbourne
- Brief Summary
A two-arm, individual participant randomised controlled, assessor-blinded trial in 7 MND care centres across Australia will be undertaken.
- Detailed Description
Non-invasive ventilation (NIV) is a treatment that uses positive pressure delivered via a face mask or mouthpiece to assist a person to breathe. It can be used as a long-term treatment for people whose breathing is failing - usually due to chronic conditions that produce weakness of the respiratory muscles such as motor neurone disease / amyotrophic lateral sclerosis \[MND/ALS\]chronic obstructive pulmonary disease). Most people with MND/ALS use NIV at night initially. Even though NIV may improve survival and function, many are unable to use it for more than 4 hours per day (which is considered a threshold amount of use in order to gain a benefit) and many others are unable to tolerate it at all. Our team has recently provided evidence that specific and individualised titration of NIV leads to better outcomes in people with MND. This previous trial determined that the use of a sleep study (also called 'polysomnography') can improve the way people are initially set up with NIV. This study will replicate and extend the single site study in a large, multi-centre randomised controlled trial (RCT) across multiple sites This multi-centre RCT will also include a 12-month follow-up period to evaluate longer-term outcomes.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 244
- Age >18 years
- Clinical indication to commence long term NIV
- Confirmed clinical diagnosis of underlying condition
- Medically unstable
- Hypoventilation attributable to medications with sedative/respiratory depressant side- effects
- Use of NIV for more than 1 month in the previous 3 months
- Inability to provide informed consent
- Previous intolerance of NIV
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Intervention Intervention polysomnography This trial of PSG-assisted commencement of non-invasive ventilation (NIV) in motor neurone disease (MND) follows the methodology of our previous single-site study (Hannan et al 2019 ERJ), with the addition of an open label cohort that extends until (the earlier of) 12 months or death. After empirical NIV set-up and an acclimatisation period (3 weeks), participants will undergo single night in-laboratory polysomnography (PSG). The PSG will be performed and supervised by a sleep scientist. In the intervention group, the "intervention" PSG results will be used to adjust/titrate NIV settings to optimize ventilation and improve synchrony between the patient and the NIV device. Participants will be asked to continue to use NIV as prescribed for the subsequent 7 week intervention period. Control Sham polysomnography The participants allocated to the control group will also be asked to attend a single night in-laboratory PSG. The NIV settings will not be adjusted throughout the PSG ("sham" PSG). Participants in the control group will retain their original settings after the sham PSG, and will be asked to continue to use NIV in this manner for the subsequent 7 week intervention period.
- Primary Outcome Measures
Name Time Method Adherence with NIV Change during the acclimatization period (~3 weeks) and during the NIV treatment period (~7-8 weeks) (approx. 10 weeks total per participant). Defined as using NIV \> 4 hours/day during the NIV treatment period.
- Secondary Outcome Measures
Name Time Method Intolerance of NIV Change during the acclimatization period (~ 3 weeks) and during the NIV treatment period (~7-8 weeks) (approx. 10 weeks total per participant). Defined as cessation of NIV during the NIV treatment period and/or \< 4 hours.
Respiratory function During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement as able. Forced expiratory volume in 1 second \[FEV1\], forced vital capacity \[FVC\]
Maximal inspiratory/expiratory pressure During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement as able. 'MIPs/MEPs'.
Arousal index (during polysomnography) During the baseline (following the ~3 week acclimatisation period) and during the follow-up assessment (~ week 3 + 7). Cohort: Not Collected. Defined as the number of electroencephalogram (EEG) arousals observed per hour of total sleep time (TST).
Asynchrony index (during polysomnography) During the baseline (following the ~3 week acclimatisation period) and during the follow-up assessment (~ week 3 + 7). Cohort: Not Collected. Defined as the number of asynchrony events per hour of sleep.
Health-related quality of life - Severe Respiratory Insufficient Questionnaire (SRI) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. A measure of health-related quality of life.
Usual care and the barriers and enablers to undertaking the intervention At trial commencement (start of RCT) and trial end (end of RCT; approx. 4 to 5 years). Multidisciplinary clinician focus groups at each recruitment site.
Carer burden - Caregiver Burden Scale (CBS) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. A measure of caregiver burden. Rated ona scale from 0 (never) to 4 (nearly always), with higher scores indicating greater carer burden.
Cost effectiveness of the intervention Throughout the trial period (approx. 5 years) (retrospective analysis). Economic evaluation using MBS/PBS data.
Experience of receiving the intervention and the barriers and enablers to the PSG and NIV usage At trial end (end of RCT; approx. 4 to 5 years) Participant semi-structured interviews.
Sniff nasal pressure During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement as able. 'SNIP'.
Total sleep time (during polysomnography) During the baseline (following the ~3 week acclimatisation period) and during the follow-up assessment (~ week 3 + 7). Cohort: Not Collected. Total amount of time asleep in minutes.
Asynchrony sub-indices (during polysomnography) During the baseline (following the ~3 week acclimatisation period) and during the follow-up assessment (~ week 3 + 7). Cohort: Not Collected. Ineffective efforts, double-trigger etc.
Dyspnoea Amyotrophic Lateral Sclerosis (DALS-15) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. A measure of breathlessness in people with ALS/MND.
Functional rating - Amyotrophic Lateral Sclerosis Functional Rating Scale (Revised) (ALSFRS) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. A clinical measure of functional rating in people with ALS/MND. Minimum score: 0, maximum score: 40. The higher the score the more function is retained.
Daytime somnolence - Karolinska Sleepiness Scales (KSS) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. The KSS is rating of the current daytime sleepiness state using a 9-point scale (1 = very alert to 9 = very sleepy, fighting sleep).
Usual clinical care practices At trial commencement and trial end. Multidisciplinary clinician surveys at each recruitment site.
Oxygen indices (during polysomnography) During the baseline (following the ~3 week acclimatisation period) and during the follow-up assessment (~ week 3 + 7). Cohort: Not Collected. Multiple measures to summarise oxygenation as one single outcome including oxygen desaturation index (defined as the total number of oxygen desaturation episodes \[= 4%\] per hour of total), sleep time, nadir SpO2, and time with SpO2 \< 90%, area under the curve and others.
% rapid eye movement (REM) sleep (during polysomnography) During the baseline (following the ~3 week acclimatisation period) and during the follow-up assessment (~ week 3 + 7). Cohort: Not Collected. Percentage of sleep characterised by eye movement, relaxation of the body, faster. respiration, and increased brain activity
Health-related quality of life - Assessment of Quality of Life (8-Dimension-AQoL) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. A measure of health-related quality of life.
Health-related quality of life - Calgary Sleep Apnoea Quality of Life Index (SAQLI) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. A measure of health-related quality of life.
Daytime somnolence - Epworth Sleepiness Scale (ESS) During the baseline (~week 0) and during the follow-up assessment (~ week 3 + 7). Cohort: At 3, 6 and 12 months following RCT commencement. A measure of daytime sleepiness.
% slow wave sleep (SWS) (during polysomnography) During the baseline (following the ~3 week acclimatisation period) and during the follow-up assessment (~ week 3 + 7). Cohort: Not Collected. Percentage of 'deep sleep'.
Sleep quality - Pittsburgh Sleep Quality Index (PSQI) RCT: During the baseline and during the follow-up assessment. Cohort: At 3, 6 and 12 months following RCT commencement. A measure of sleep quality.
Experience of the person they are caring for receiving the intervention and the barriers and enablers to the PSG and NIV usage At trial end (end of RCT; approx. 4 to 5 years). Caregiver semi-structured interviews.
Trial Locations
- Locations (13)
Flinders Medical Centre
🇦🇺Adelaide, Australia
The Prince Charles Hospital
🇦🇺Brisbane, Australia
Austin Health
🇦🇺Melbourne, Australia
Motor Neurone Disease Australia
🇦🇺Canberra, Australia
Australian MND Registry
🇦🇺Melbourne, Australia
FightMND
🇦🇺Melbourne, Australia
Institute for Breathing and Sleep
🇦🇺Melbourne, Australia
University of Melbourne
🇦🇺Melbourne, Australia
Monash University
🇦🇺Melbourne, Australia
Macquarie University
🇦🇺Sydney, Australia
Royal Prince Alfred Hospital
🇦🇺Sydney, Australia
Sir Charles Gairdner Hospital
🇦🇺Perth, Australia
Westmead Hospital
🇦🇺Sydney, Australia