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Trial registered on ANZCTR


Registration number
ACTRN12618001579280
Ethics application status
Approved
Date submitted
18/09/2018
Date registered
24/09/2018
Date last updated
1/12/2023
Date data sharing statement initially provided
23/09/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Evaluation of LGT-371 as a treatment for obstructive sleep apnoea: A pilot study
Scientific title
The effects of LGT-371 on obstructive sleep apnoea (OSA) severity in men and women with moderate-to-severe OSA
Secondary ID [1] 296003 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Obstructive sleep apnoea 309523 0
Condition category
Condition code
Respiratory 308352 308352 0 0
Sleep apnoea

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
LGT-371 (single evening dose [one night], mono therapy [400mg], oral capsule, 1-week washout between conditions)

To ensure 100% adherence, all drugs to be administered by research staff during the treatment and placebo in-laboratory sleep studies (polysomnography) performed at the Monash University Sleep Research Facility
Intervention code [1] 312332 0
Treatment: Drugs
Comparator / control treatment
Placebo (lactose) - (single evening dose [one night], mono therapy [400mg], oral capsule, 1-week washout between conditions)
Participants will act as their own controls in a cross-over design
Control group
Placebo

Outcomes
Primary outcome [1] 307339 0
Sleep apnoea severity using the apnoea/hypopnoea index from the overnight polysomnogram
Timepoint [1] 307339 0
Single acute overnight sleep studies (placebo vs. drug)
Primary outcome [2] 307340 0
Loop Gain (LG) determined during sleep from the overnight polysomnogram [measured using the method described by Terrill et al (2015)].
Timepoint [2] 307340 0
Single acute overnight sleep studies (placebo vs. drug)
Secondary outcome [1] 351519 0
Subjective sleepiness measured with the Stanford Sleepiness Scale
Timepoint [1] 351519 0
Single acute overnight sleep studies (placebo vs. drug). 30 mins post-awakening from overnight sleep study
Secondary outcome [2] 351520 0
Subjective sleep quality will be assessed by asking participants to assign a rating score indicating how they felt they slept during the night of the overnight polysomnogram study (worst:0, best:10)
Timepoint [2] 351520 0
Single acute overnight sleep studies (placebo vs. drug). 30 mins post-awakening from overnight sleep study
Secondary outcome [3] 351521 0
Blood pressure (diastolic and systolic) measured with an automatic sphygmomanometer
Timepoint [3] 351521 0
Single acute overnight sleep studies (placebo vs. drug). Measured 10 minutes before 'lights out' of each overnight sleep study period; and then again at 10 minutes post-awakening in the morning after each night study
Secondary outcome [4] 351522 0
Heart rate measured with an automatic sphygmomanometer
Timepoint [4] 351522 0
Single acute overnight sleep studies (placebo vs. drug). Measured 10 minutes before 'lights out' of each overnight sleep study period; and then again at 10 minutes post-awakening in the morning after each night study.
Secondary outcome [5] 351523 0
Sleep efficiency from the overnight polysomnogram
Timepoint [5] 351523 0
Single acute overnight sleep studies (placebo vs. drug)
Secondary outcome [6] 351524 0
Hypoxemia from the overnight polysomnogram measured using oximetry
Timepoint [6] 351524 0
Single acute overnight sleep studies (placebo vs. drug)
Secondary outcome [7] 351525 0
Arousal index from the overnight polysomnogram
Timepoint [7] 351525 0
Single acute overnight sleep studies (placebo vs. drug)
Secondary outcome [8] 352049 0
Awake chemoreceptor sensitivity as measured by a chemoreflex test using hypoxic and hypercapnic gas mixtures.
Timepoint [8] 352049 0
Performed in the evening after placebo/active drug administration (placebo vs. drug)

Eligibility
Key inclusion criteria
Otherwise healthy men and women with moderate-to-severe obstructive sleep apnoea
Minimum age
18 Years
Maximum age
70 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
•Medical and concurrent medication exclusions in accordance with the most recently published Summary of Product Characteristics (SPC) for LGT-371
•Concurrent or recent (within the past month) use of any medication known to influence sleep, arousal, circadian rhythm, breathing or muscle function
•For women: Pregnancy or breast feeding.
•Occupation or life situation that may be put at risk by participation in the study
•History of shift work or rotating shifts in the month prior
•Involvement as a driver in a motor vehicle accident during the past 2 years where the cause of the accident was attributed to driver sleepiness
•Inability to sleep supine

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central randomisation by computer
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Crossover
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
17/01/2022
Actual
6/06/2022
Date of last participant enrolment
Anticipated
1/12/2022
Actual
11/05/2023
Date of last data collection
Anticipated
30/12/2022
Actual
17/05/2023
Sample size
Target
15
Accrual to date
Final
15
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 300597 0
University
Name [1] 300597 0
Monash University
Country [1] 300597 0
Australia
Primary sponsor type
University
Name
Monash University
Address
Sleep and Circadian Medicine Laboratory
Ground Floor, BASE Facility
264 Ferntree Gully Road
Notting Hill, Victoria, 3168
Country
Australia
Secondary sponsor category [1] 300099 0
None
Name [1] 300099 0
Address [1] 300099 0
Country [1] 300099 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 301382 0
Monash University Human Research Ethics Committee
Ethics committee address [1] 301382 0
Monash University Human Research Ethics Committee (MUHREC)
Room 111, Chancellery Building D,
26 Sports Walk, Clayton Campus
Research Office
Monash University VIC 3800
Ethics committee country [1] 301382 0
Australia
Date submitted for ethics approval [1] 301382 0
18/09/2018
Approval date [1] 301382 0
27/11/2019
Ethics approval number [1] 301382 0
16780
Ethics committee name [2] 309625 0
Monash Health HREC
Ethics committee address [2] 309625 0
Monash Health
Level 2, I Block
Monash Medical Centre
246 Clayton Road
Clayton Victoria 3168
Ethics committee country [2] 309625 0
Australia
Date submitted for ethics approval [2] 309625 0
28/02/2019
Approval date [2] 309625 0
27/11/2019
Ethics approval number [2] 309625 0
RES-19-0000-092A

Summary
Brief summary
Recent studies show that the incidence and severity of obstructive sleep apnoea (OSA) are influenced by the gain or sensitivity of the negative feedback loop controlling breathing (i.e. the loop gain), and that this influence is independent of the contributions made by anatomical and neuromuscular factors such as abnormalities of the soft palate or dysfunction of the oropharyngeal musculature. Accordingly, it follows that if we were to administer a drug that lowers an individuals loop gain, we would reduce the propensity for OSA and thereby ameliorate some, if not all, of the symptoms of sleep disordered breathing.

We have evidence that administration of an orally-available drug, LGT-371, does indeed reduce the sensitivity of the peripheral and/or central chemoreceptors (and thereby overall loop gain) in an animal model of sleep disordered breathing and that it reduces the severity of sleep apnoea in the model. We now plan to test whether LGT-371 has a similar action in human subjects with OSA.

The primary aim of this study is to assess the effect that LGT-371 has on sleep apnoea severity, loop gain and chemoreceptor sensitivity compared to placebo. Additional measures of sleep apnoea severity, cardiovascular markers (blood pressure & heart rate) and subjective sleepiness will also be assessed as secondary outcomes.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 3077 3077 0 0
/AnzctrAttachments/375942-Terrill PI, et al. Eur. Respir. J. 2015 (45, 408-418).pdf (Publication)

Contacts
Principal investigator
Name 86826 0
Dr Bradley Edwards
Address 86826 0
Department of Physiology and School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences, Monash University
264 Ferntree Gully Road, Notting Hill,
VIC 3168
Country 86826 0
Australia
Phone 86826 0
+613 9905 0187
Fax 86826 0
Email 86826 0
[email protected]
Contact person for public queries
Name 86827 0
Bradley Edwards
Address 86827 0
Department of Physiology and School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences, Monash University
264 Ferntree Gully Road, Notting Hill,
VIC 3168
Country 86827 0
Australia
Phone 86827 0
+613 9905 0187
Fax 86827 0
Email 86827 0
[email protected]
Contact person for scientific queries
Name 86828 0
Bradley Edwards
Address 86828 0
Department of Physiology and School of Psychological Sciences
Faculty of Medicine, Nursing and Health Sciences, Monash University
264 Ferntree Gully Road, Notting Hill,
VIC 3168
Country 86828 0
Australia
Phone 86828 0
+613 9905 0187
Fax 86828 0
Email 86828 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.