None listed
Conditions
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.
Interventions
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
Sponsors
Monash University
Study design
Allocation
Randomised controlled trial
Intervention model
Crossover
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
Otherwise healthy men and women with moderate-to-severe obstructive sleep apnoea
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
Outcome results
None listed