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Trial registered on ANZCTR


Registration number
ACTRN12618001579280p
Ethics application status
Submitted, not yet approved
Date submitted
18/09/2018
Date registered
24/09/2018
Date last updated
28/09/2018
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 [100mg], 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 (cellulose) - (single evening dose [one night], mono therapy [100mg], 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
Change in awake chemoreceptor sensitivity as measured by a chemoreflex test using hypoxic and hypercapnic gas mixtures.
Timepoint [2] 307340 0
Performed in the evening before and after placebo/active drug administration
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
Difference in average values of Loop Gain (LG) during sleep (measured using the method of Terrill et al (2015) in the presence or absence of LGT-371 (Study Night 1 vs Study Night 2)
Timepoint [8] 352049 0
Single acute overnight sleep studies (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
Gender
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
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC

Funding & Sponsors
Funding source category [1] 300597 0
University
Name [1] 300597 0
Monash University
Address [1] 300597 0
Wellington Road & Blackburn Road,
Monash University
Clayton, Victoria, 3800
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
Submitted, not yet 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
Ethics approval number [1] 301382 0
16780

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

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
bradley.edwards@monash.edu
Contact person for public queries
Name 86827 0
Dr 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
bradley.edwards@monash.edu
Contact person for scientific queries
Name 86828 0
Dr 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
bradley.edwards@monash.edu

No data has been provided for results reporting
Summary results
Not applicable