Motor Neuron Disease / Amyotrophic Lateral Sclerosis
Conditions
Keywords
Non-invasive ventilation, Polysomnography, Sleep study, Amyotrophic lateral sclerosis, Chronic respiratory failure
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.
Interventions
OTHERIntervention polysomnography
Please refer to 'Arms: Intervention' section.
OTHERSham polysomnography
Please refer to 'Arms: Control' section.
Sponsors
Austin Hospital, Melbourne Australia
Institute for Breathing and Sleep, Australia
Royal Prince Alfred Hospital, Sydney, Australia
Macquarie University, Australia
Macquarie Health
Western Sydney Local Health District
Flinders Medical Centre
Sir Charles Gairdner Hospital
The Prince Charles Hospital
Monash University
Motor Neurone Disease Australia
FightMND
Australian Motor Neurone Disease Registry
Calvary Bethlehem
Perron Institute for Neurological and Translational Science
University of Melbourne
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
The attending sleep scientist will refer to a database that reveals (statistician-generated) participant's treatment allocation. The sleep scientist will not reveal the treatment allocation to the Clinical team, Research team or the participant. Centralised allocation concealment will be ensured through the Adept/REDCap trial database.
Intervention model description
Randomised controlled trial with 12 month cohort follow-up
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age \>18 years * Clinical indication to commence long term NIV * Confirmed clinical diagnosis of underlying condition
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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'. |
| 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'. |
| 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. |
| 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. |
| 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. |
| % 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 |
| % 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'. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| Usual clinical care practices | At trial commencement and trial end. | Multidisciplinary clinician surveys at each recruitment site. |
| 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. |
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Arterial Blood Gas (ABG) (during polysomnography) | RCT: During the baseline (following the acclimatisation period) and during the follow-up assessment. Cohort: Not Collected. | Arterial Blood Gas |
Countries
Australia
Contacts
Primary ContactDavid Berlowitz, PhD
Outcome results
None listed