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Polysomnographic Titration of Non-invasive Ventilation in Motor Neurone Disease (3TLA)

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ClinicalTrials.gov Identifier: NCT05136222
Recruitment Status : Recruiting
First Posted : November 29, 2021
Last Update Posted : June 23, 2022
Sponsor:
Collaborators:
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
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Motor Neuron Disease / Amyotrophic Lateral Sclerosis Other: Intervention polysomnography Other: Sham polysomnography Not Applicable

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 244 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomised controlled trial with 12 month cohort follow-up
Masking: Quadruple (Participant, Care Provider, 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.

Primary Purpose: Treatment
Official Title: A Multi-centre Randomised Controlled Trial of Polysomnographic Titration of Non-invasive Ventilation in Motor Neurone Disease (PSG4NIVinMND; 3, Three Letter Acronyms [3TLA])
Actual Study Start Date : December 15, 2021
Estimated Primary Completion Date : February 28, 2026
Estimated Study Completion Date : February 28, 2028


Arm Intervention/treatment
Experimental: Intervention

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.

Other: Intervention polysomnography
Please refer to 'Arms: Intervention' section.

Placebo Comparator: Control
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.
Other: Sham polysomnography
Please refer to 'Arms: Control' section.




Primary Outcome Measures :
  1. Adherence with NIV [ Time Frame: 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 :
  1. Intolerance of NIV [ Time Frame: 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.

  2. Respiratory function [ Time Frame: 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]

  3. Maximal inspiratory/expiratory pressure [ Time Frame: 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'.

  4. Sniff nasal pressure [ Time Frame: 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'.

  5. Arousal index (during polysomnography) [ Time Frame: 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).

  6. Asynchrony index (during polysomnography) [ Time Frame: 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.

  7. Oxygen indices (during polysomnography) [ Time Frame: 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.

  8. Total sleep time (during polysomnography) [ Time Frame: 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.

  9. % rapid eye movement (REM) sleep (during polysomnography) [ Time Frame: 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

  10. % slow wave sleep (SWS) (during polysomnography) [ Time Frame: 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'.

  11. Asynchrony sub-indices (during polysomnography) [ Time Frame: 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.

  12. Dyspnoea Amyotrophic Lateral Sclerosis (DALS-15) [ Time Frame: 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.

  13. Health-related quality of life - Severe Respiratory Insufficient Questionnaire (SRI) [ Time Frame: 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.

  14. Health-related quality of life - Assessment of Quality of Life (8-Dimension-AQoL) [ Time Frame: 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.

  15. Health-related quality of life - Calgary Sleep Apnoea Quality of Life Index (SAQLI) [ Time Frame: 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.

  16. Functional rating - Amyotrophic Lateral Sclerosis Functional Rating Scale (Revised) (ALSFRS) [ Time Frame: 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.

  17. Sleep quality - Pittsburgh Sleep Quality Index (PSQI) [ Time Frame: 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.

  18. Daytime somnolence - Epworth Sleepiness Scale (ESS) [ Time Frame: 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.

  19. Daytime somnolence - Karolinska Sleepiness Scales (KSS) [ Time Frame: 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).

  20. Carer burden - Caregiver Burden Scale (CBS) [ Time Frame: 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.

  21. Cost effectiveness of the intervention [ Time Frame: Throughout the trial period (approx. 5 years) (retrospective analysis). ]
    Economic evaluation using MBS/PBS data.

  22. Usual clinical care practices [ Time Frame: At trial commencement and trial end. ]
    Multidisciplinary clinician surveys at each recruitment site.

  23. Usual care and the barriers and enablers to undertaking the intervention [ Time Frame: 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.

  24. Experience of receiving the intervention and the barriers and enablers to the PSG and NIV usage [ Time Frame: At trial end (end of RCT; approx. 4 to 5 years) ]
    Participant semi-structured interviews.

  25. Experience of the person they are caring for receiving the intervention and the barriers and enablers to the PSG and NIV usage [ Time Frame: At trial end (end of RCT; approx. 4 to 5 years). ]
    Caregiver semi-structured interviews.


Other Outcome Measures:
  1. Arterial Blood Gas (ABG) (during polysomnography) [ Time Frame: RCT: During the baseline (following the acclimatisation period) and during the follow-up assessment. Cohort: Not Collected. ]
    Arterial Blood Gas



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05136222


Contacts
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Contact: David Berlowitz, PhD +613 9496 3871 david.berlowitz@austin.org.au

Locations
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Australia
Flinders Medical Centre Not yet recruiting
Adelaide, Australia
Contact: Dr Vinod Aiyappan         
The Prince Charles Hospital Not yet recruiting
Brisbane, Australia
Contact: Dr Deanne Curtin         
Motor Neurone Disease Australia Not yet recruiting
Canberra, Australia
Contact: Dr Gethin Thomas         
Austin Health Recruiting
Melbourne, Australia
Contact: Associate Professor Mark Howard         
Australian MND Registry Not yet recruiting
Melbourne, Australia
Contact: A/Professor Paul Talman         
FightMND Not yet recruiting
Melbourne, Australia
Contact: Dr Bec Sheean         
Institute for Breathing and Sleep Not yet recruiting
Melbourne, Australia
Contact: Associate Professor Mark Howard         
Monash University Not yet recruiting
Melbourne, Australia
Contact: Professor Natasha Lannin         
University of Melbourne Not yet recruiting
Melbourne, Australia
Contact: Professor David Berlowitz         
Sir Charles Gairdner Hospital Not yet recruiting
Perth, Australia
Contact: Dr Bhajan Singh         
Macquarie University Not yet recruiting
Sydney, Australia
Contact: Professor Dominic Rowe         
Royal Prince Alfred Hospital Not yet recruiting
Sydney, Australia
Contact: Dr Amanda Piper         
Westmead Hospital Not yet recruiting
Sydney, Australia
Contact: Dr John Wheatley         
Sponsors and Collaborators
University of Melbourne
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
Investigators
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Study Chair: Abbey Sawyer, PhD University of Melbourne
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Responsible Party: University of Melbourne
ClinicalTrials.gov Identifier: NCT05136222    
Other Study ID Numbers: CT20020
First Posted: November 29, 2021    Key Record Dates
Last Update Posted: June 23, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Dataset in de-identified form will be shared on request to corresponding author.
Time Frame: 5 years from study completion.
Access Criteria:

Subject to optional consent, where participants give permission for data to be used for the purpose of:

  1. The ethically approved research project only.
  2. This ethically approved research project and any closely related future research projects.
  3. This ethically approved research project and any future research projects that may or may not be related to this project.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by University of Melbourne:
Non-invasive ventilation
Polysomnography
Sleep study
Amyotrophic lateral sclerosis
Chronic respiratory failure
Additional relevant MeSH terms:
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Motor Neuron Disease
Amyotrophic Lateral Sclerosis
Sclerosis
Pathologic Processes
Neurodegenerative Diseases
Nervous System Diseases
Neuromuscular Diseases
Spinal Cord Diseases
Central Nervous System Diseases
TDP-43 Proteinopathies
Proteostasis Deficiencies
Metabolic Diseases