Effects of Eszopiclone and Lemborexant in People With Obstructive Sleep Apnoea (OSA) With a Low Arousal Threshold Who Have Difficulty Maintaining or Falling Asleep (ELOSA): A Double-blind, Placebo-controlled, Randomised, Trial.
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 15
- 试验地点
- 2
- 主要终点
- Change in OSA severity (eszopiclone and lemborexant night vs. placebo night)
研究概览
简要总结
Insomnia and obstructive sleep apnoea (OSA) are very common conditions, collectively estimated to affect 2 billion people globally, and share many of the same symptoms. It is also common for people to have both insomnia and sleep apnoea (COMISA). Indeed, 30 to 40% of patients with chronic insomnia also fulfil the diagnostic criteria for OSA. These people can be particularly challenging to treat with conventional therapy approaches.
People get OSA for different reasons. One key cause is waking up too easily to minor airway narrowing episodes (a low arousal threshold).
Accordingly, this study aims to increase the arousal threshold using a combination approach with a GABAergic and an orexin agent in appropriately selected individuals (i.e., the clinically relevant group of people with OSA with a low arousal threshold and difficulty maintain or initiating sleep). Sleep, breathing and next day performance will be compared across two monitored overnight sleep studies (placebo vs the study drugs).
详细描述
Background:
Insomnia and obstructive sleep apnoea (OSA) are very common conditions, collectively estimated to affect 2 billion people globally, and share many of the same symptoms. It is also common for people to have both insomnia and sleep apnoea (COMISA). Indeed, 30 to 40% of patients with chronic insomnia also fulfil the diagnostic criteria for OSA. These people can be particularly challenging to treat with conventional therapy approaches.
OSA is characterised by repeated narrowing and closure of the upper airway during sleep, desaturation in oxygen levels, and fragmented sleep. OSA is a heterogeneous disease, with anatomical crowding of the upper airway and at least three distinct non-anatomical endotypes. The non-anatomical OSA endotypes include high loop gain (unstable control of breathing), poor upper airway dilator muscle function, and a low arousal threshold (ArTH- waking up too easily to minor airway narrowing events). Each OSA endotype represents a novel therapeutic target. Adding to the complexity of OSA, more than one endotype can contribute to a person's OSA. While the first line treatment for OSA, continuous positive airway pressure (CPAP) is efficacious, long-term compliance is only 40 to 70%. Those with a low ArTH endotype have markedly lower CPAP uptake and compliance.
Indeed, people with a low ArTH endotype experience frequent cortical arousals (awakenings) leading to fragmented and non-restorative sleep. Frequent cortical arousals prevent transitioning into deeper sleep states that are characterised by more stable breathing. Thus, strategies to increase the arousal threshold to stabilise breathing and reduce OSA severity in people who wake up easily (low ArTH) have been investigated as a novel therapeutic target. For example, commonly used hypnotic agents such as eszopiclone and trazodone can increase the arousal threshold and reduce OSA severity in people with a low ArTH. More recently, we have shown that 50mg quetiapine also improves sleep and reduces OSA severity in people with OSA who report difficulty maintaining sleep. However, the extent to which common hypnotic agents increase the arousal threshold in people with OSA is modest at best (~20%). This limits the therapeutic efficacy for people with OSA.
Orexin has been identified as an important sleep wake modulator. Accordingly, new orexin antagonists have been developed as novel sleep promotion aids for the treatment of insomnia. For example, the orexin antagonist, Lemborexant, has been shown to be safe and efficacious for the treatment of insomnia including in the elderly and people with OSA.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Moderate or more difficulty "staying or initiating asleep" score on the Insomnia Severity Index questionnaire
- •Obstructive Sleep Apnoea (OSA), Apnoea Hypopnea Index ≥ 10 events/hour
- •Low arousal respiratory threshold OSA endotype
- •BMI ≤35 kg/m2
排除标准
- •Concomitant medications that interact or are contraindicated with eszopiclone, zopiclone, and Lemborexant
- •Concomitant medications known to influence breathing, sleep, arousal, or muscle physiology
- •Current pregnancy or breast-feeding
- •Current or recent other medical conditions likely to affect results or safety
研究组 & 干预措施
Eszopiclone 3mg and lemborexant 10mg
Both Eszopiclone 3mg and Lemborexant 10mg in the form of capsules taken before bedtime. Dosages is taken on one instance for one night only.
干预措施: Eszopiclone 3 mg (Drug)
Placebo
Placebo capsules that look exactly like the study drugs, taken before bedtime. Dosage is taken on one instance for one night only.
干预措施: Placebo (Drug)
Eszopiclone 3mg and lemborexant 10mg
Both Eszopiclone 3mg and Lemborexant 10mg in the form of capsules taken before bedtime. Dosages is taken on one instance for one night only.
干预措施: Lemborexant 10mg (Drug)
结局指标
主要结局
Change in OSA severity (eszopiclone and lemborexant night vs. placebo night)
时间窗: Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.
OSA severity as measured by the apnoea hypopnea index (units: number of respiratory events/h sleep) during overnight in-laboratory polysomnography.
次要结局
- Change in nadir overnight hypoxemia (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in mean overnight hypoxemia (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in time below 90% blood arterial oxygen saturation (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in sleep efficiency (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in arousal index (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in respiratory control (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in the respiratory arousal threshold (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in airway collapsibility (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in pharyngeal muscle response (eszopiclone and lemborexant night vs. placebo night)(Two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Baseline OSA endotype and whether they are associated with changes in OSA severity(Baseline sleep study)
- Change in next morning balance (eszopiclone and lemborexant night vs. placebo night)(Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in perceived sleepiness (eszopiclone and lemborexant night vs. placebo night)(Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in driving simulator performance (eszopiclone and lemborexant night vs. placebo night)(Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
- Change in psycho-motor vigilance (eszopiclone and lemborexant night vs. placebo night)(Next morning following two non-consecutive single night sleep studies (eszopiclone and lemborexant night vs. placebo night) up to one month apart.)
研究者
Professor Danny Eckert
Director, Adelaide Institute for Sleep Health, Professor, College of Medicine and Public Health and Matthew Flinders Fellow, Flinders University
Flinders University