The LENS Study: Efficacy and Safety of Lemborexant for Patients With Nocturia
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Change in mean nocturia episodes per 24 hours
研究概览
简要总结
Nocturia is defined by doctors as getting up one or more times a night to use the bathroom, where you were asleep before going to use the washroom and then going back to sleep afterward. People who experience this condition describe it was one of their biggest problems. This condition is very common as people get older and can seriously affect older peoples quality of life including disruptions to sleep, daily functioning, risk of falls and even early death.
详细描述
Nocturia, defined by the International Continence Society (ICS) as the complaint of waking up one or more times per night to void, with each void typically preceded and followed by sleep (4,5). Nocturia is not only described as one of the most bothersome of all urinary symptoms, but also as one of the most prevalent, with devastating impacts on quality of life (QOL)(5,6). Although nocturia is relatively infrequent among young adults, especially young women (compared to young men), its prevalence tends to increase with age. In individuals aged 60 years or older, reported rates can reach as high as 70%, with over 36% reporting the need to wake up 2 or more times per night to void (7). A recently published meta-analysis reported associations between nocturia and risk of falls, fractures, and early mortality (8).
The causes of nocturia are complex and multifactorial, including nocturnal polyuria (NP - defined as excessive urine production during sleep), sleep disorders (such as insomnia, sleep apnea), metabolic conditions (such as diabetes, uncontrolled hypertension), bladder dysfunctions (OAB or BPE), lifestyle factors (fluid or alcohol intake), or a combination of these conditions (7,9,10).
In Canada, the increasing proportion of older adults, projected to constitute approximately 25% of the population by 2041, poses a notable public health concern owing to the association between nocturia and aging and the potential public health costs of managing the condition (11,12). Bothersome nocturia, defined clinically as two or more nightly voids, is more than just an inconvenience. It has notable clinical implications, including impaired cognitive function during the day, fatigue, falls, depression, and a considerable decrease in health-related quality of life (HRQOL), highlighting the need for new treatment approaches.
Rationale for the study:
The results of a recent study conducted with 32 insomnia patients with nocturia who typically awoke two or more times per night to void demonstrated that 4 weeks of once-daily 5mg Lemborexant significantly improved multiple clinical parameters related to sleep quality and nocturia (13). Nocturia frequency was significantly reduced from a mean of 3.4 episodes per night to 2.3 episodes (p<0.001). Additionally, measures from the frequency-volume chart showed a significant increase in mean single voided urine volume at night from 182.5ml to 222.3 ml (p<0.001). The mean duration of undisturbed sleep also increased from 105.3 minutes to 174.8 minutes (p < 0.001), approaching the three-hour period of deep sleep vital for older adults. Participant quality of life, assessed by the Nocturia Quality of Life Questionnaire (N-QOL), significantly improved from 49.6% to 64.8% (p<0.001).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥65 years
- •Has nocturia as determined by ICS criteria (ICIQ-N)
- •Has Nocturia, after 4 weeks of conservative treatment (fluid advice, leg elevation, sodium restriction, medication review, mild compression stockings where relevant), indicates a score of ≥4 on question 4b of the validated ICIQ Nocturia module [https://iciq.net/iciq-n] - (indication of bother rating of 4-10)
- •Participants with prior treatment for concomitant OAB should have been on stable doses of therapy for 12 weeks prior to inclusion.
排除标准
- •Participant has a 24h polyuria (>3L), measured by a 7-day bladder diary
- •Participant has a post-void residual (>250mL), measured by ultrasound following void from a comfortably full bladder
- •Participant has an acute symptomatic UTI (can be treated and rescreened for inclusion)
- •The participant has known untreated sleep apnoea, or highly likely OSA according to the validated STOP-BANG questionnaire (score 5-8)
- •The participant has significant heart failure (NYHA C/D)
- •The participant has severe renal impairment (eGFR <30mL/min), severe hepatic impairment (Child-Pugh class 3)
- •The participant is taking hypnotics
- •The participant is taking strong CYP3A inducers such as rifampin, carbamazepine, St. John's wort
- •The participant has a known drug allergy to Lemborexant or its constituents
- •The participant has cognitive impairment of a degree which, in the opinion of the investigator, is likely to impair the ability to adhere to trial requirements
- •The participant is unwilling to abstain from alcohol consumption for the period of the study
- •Other condition(s) which would preclude inclusion.
研究组 & 干预措施
Sequence B: Placebo then Lemborexant
Matching placebo at bedtime for 6 weeks (1 tablet weeks 1-3, optional increase to 2 tablets weeks 4-6), then 2 week washout, then Lemborexant for 6 weeks
干预措施: Placebo (Drug)
Sequence A: Lemborexant then Placebo
Lemborexant at bedtime for 6 weeks (5 mg weeks 1-3), optional uptitration to 10 mg (weeks 4-6), and then 2 week washout, then matching placebo for 6 weeks.
干预措施: Lemborexant tablets (Drug)
结局指标
主要结局
Change in mean nocturia episodes per 24 hours
时间窗: 42 Days
Change in mean nocturia episodes per 24 hours, measured by a 7-day/night bladder diary between baseline and the end of each treatment period. Participants will record the time and volume of each void (day and night) for 7 consecutive days at baseline (prior to randomization) and at week 6 (the final treatment weeks: days 35-42) of each treatment period.
次要结局
- Change in mean nocturia urinary frequency(42 days)
- Change in Epiworth Sleepiness Scale (ESS)(42 days)
- Change in nocturia associated quality of life(42 days)
- Change in Insomnia Severity Index (ISI)(42 days)
- Change in mean reported first uninterrupted sleep period (FUSP)(42 days)
- Change in patient self assessment of condition (PGI)(42 days)
- Patient reported adverse events(56 days)