双重的Orexin受体拮抗剂,可减少失眠的成年人神经退行性的生物标志物。 (Neuro-DORA)
一种双重或毒素受体拮抗剂,可减少失眠症障碍成人神经退行性的生物标志物:一项随机的安慰剂对照跨界研究。
The goal of this clinical trial is to explore the potential neuroprotective benefits of a dual orexin receptor antagonist (DORA) in adults with insomnia. The main questions it aims to answer are:
- Does the DORA reduce blood-based phosphorylated TAU181, in adults with insomnia, when compared to placebo
- Does the DORA reduce other blood-based biomarkers of neurodegeneration, including phosphorylated TAU217, amyloid beta 40:42 ratio, Neurofilament Light Chain (NFL) and Glial Fibrillary Acidic Protein (GFAP), when compared to placebo.
Participants will:
- Take 10mg Lemborexant nightly for two weeks
- Take a matching placebo nightly for two weeks
- Visit the research institute for a screening visit and for an overnight visit at the conclusion of each study drug treatment (3 visits in total).
研究概览
详细说明
This is a randomised placebo-controlled cross-over study of a dual orexin receptor antagonist (DORA) versus placebo in adults with insomnia.
To be enrolled in the study, participants are required to complete an online pre-screening survey. Eligible participants will be directed to a separate webpage where they will be invited to review and download the Participant Information Sheet (PIS) and asked to provide their contact details and consent for a follow up call/email from the research team to book in a screening visit. At the screening visit the study team will explain the study to each participant and ensure they have had ample time prior to the visit to read and understand the PIS and have had the opportunity to ask any questions. The consent form will be signed by both the participant and a medical officer and participants will be randomised into their first treatment period; DORA (Lemborexant) or placebo.
Participants will take the treatment orally, nightly for 2 weeks. There will be a 2-4 week washout period between treatments. At the conclusion of both two-week treatment phases, participants will attend the laboratory for an overnight visit. The visit will take approximately 18 hours (including sleep time). During this visit, participants will partake in a number of assessments including HD-EEG, fNIRS, questionnaires and pupillometry. Participants will also have blood samples collected in the morning of the overnight study (hourly for four hours).
The study will recruit primarily through social media advertisements. The study will be coordinated from the Woolcock Institute of Medical Research, Sydney, Macquarie University, NSW, 2113, Australia.
研究类型
注册 (估计的)
阶段
- 阶段2
联系人和位置
学习联系方式
- 姓名:Camilla Hoyos, MPH, PhD
- 电话号码:0438801044
- 邮箱:camilla.hoyos@mq.edu.au
研究联系人备份
- 姓名:Rhearne Ryan, HScHons, PhD
- 电话号码:+61 2 9805 3274
- 邮箱:rhearne.ryan@woolcock.org.au
学习地点
-
-
New South Wales
-
Macquarie Park、New South Wales、澳大利亚、2113
- 招聘中
- Woolcock Institute of Medical Research
-
接触:
- Grigori Kaplan, PhD
- 电话号码:+61 9114 0412
- 邮箱:grigori.kaplan@sydney.edu.au
-
首席研究员:
- Camilla Hoyos, PhD
-
首席研究员:
- Brendon Yee, PhD FRACP
-
-
参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
Inclusion Criteria:
- Diagnosis of insomnia disorder as defined by the DSM-5 (difficulty initiating or maintaining sleep or waking up too early for at least 3 nights per week, for at least 3 months, with adequate opportunity and circumstances for sleep and at least one daytime impairment related to the sleep difficulty) and a score ≥15 on the ISI.
- Able to provide informed electronic consent.
- Fluent English literacy.
- Adults aged between 40-65 years.
Exclusion Criteria:
- People highly dependent on medical care as determined by a medical officer.
- Untreated moderate-severe sleep apnoea as diagnosed using in-home wrist oximetry (oxygen desaturation index>15, ongoing effectively treated sleep apnoea with insomnia will be allowed).
- Circadian disorders, narcolepsy, severe restless legs syndrome, and REM sleep behaviour disorder or uncontrolled psychiatric disorders.
- History of attempted suicide or current suicide ideation (indicated by a score >0 on Q9 of the Patient Health Questionnaire-9) at pre-screening.
- Objective cognitive decline measured by scoring ≤26 on the Montreal Cognitive Assessment (MoCA)
- Regular shift work, jet lag or trans-meridian travel (over 2h time difference) in the past week before randomisation.
- Pregnancy or lactation. Women will be advised to use contraception for the duration of the study and a urine pregnancy test will be performed when necessary.
- Any other condition that would, in the Investigator's judgment, contraindicate the patient's participation in the clinical trial due to safety concerns or compliance with clinical study procedures.
- Currently participating in or has participated in a research study of an investigational agent or device within 4 weeks of enrolment.
- Concomitant use of medicines that are inhibitors (e.g., diltiazem, fluvoxamine, fluconazole, itraconazole, verapamil), or moderate to strong inducers of CYP3A4 (e.g., carbamazepine, modafinil, phenytoin, rifampicin, St John's Wort)
- Ongoing use of anti-psychotic medication, bosentan, efavirenz, etravirine, modafinil, rifampin, carbamazepine or illicit stimulants.
- Regular use of hypnotics (including melatonin, valerian, kava, benzodiazepines and Z-drugs), and other medications that can cause additive sedation (e.g. sedating antihistamines, tricyclic antidepressants, antipsychotics) within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
- Regular use of psychostimulants (e.g., dexamfetamine, lisdexamfetamine, methylphenidate) or non-amphetamine psychostimulants (e.g., armodafinil, modafinil, atomoxetine) within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
- Use of antidepressant medications for treatment of low mood for less than one year or dose changes (escalation or tapering) or change in antidepressant medications within the past year.
- Regular use opioids within 14 days or 4-5 half-lives (whichever is longer) of starting the clinical trial.
- Ongoing use of THC- or CBD-containing products within 14 days prior to the start of the trial.
- Dependence or any other drug or alcohol dependence within the past two years (alcohol to be limited to no more than 2 standard drinks per day during trial period).
- Allergy to lactose.
学习计划
研究是如何设计的?
设计细节
- 主要用途:其他
- 分配:随机化
- 介入模型:交叉作业
- 屏蔽:四人间
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:Dual Orexin Receptor Antagonist (DORA)
10mg Lemborexant tablet taken orally, nightly for two weeks |
An orally ingested tablet containing 10mg Lemborexant taken before bedtime. The investigational product is manufactured under Good Manufacturing Practice and is compliant with the TGA Therapeutic Order #101 that stipulates quality control requirements for capsule and pill-based products used in Australia.
其他名称:
|
|
安慰剂比较:Placebo
Matching placebo tablet taken orally, nightly for two weeks |
Placebo tablets will contain similar excipients without the active ingredient (Lemborexant) and manufactured under the same condition as the active. Placebo tablets, packs and instructions will be identical in every respect to enable the double-blind study design. |
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Blood levels of TAU181
大体时间:5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
Morning blood-based phosphorylated TAU (standardised pTAU181:TAU181 ratio) |
5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Blood levels of TAU217
大体时间:5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
Morning blood-based phosphorylated TAU217, analysed within each participant. |
5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
|
Blood levels of Beta amyloid
大体时间:5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
Morning blood-based Beta Amyloid 40:42 ratio, analysed within each participant. |
5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
|
Blood levels of NFL
大体时间:5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
Morning blood-based Neurofilament Light Chain (NFL), analysed within each participant. |
5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
|
Blood levels of GFAP
大体时间:5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
Morning blood-based Fibrillary Acidic Protein (GFAP), analysed within each participant. |
5 samples hourly for 4 hours after awakening in the morning of the overnight treatment period visits (approximately 7am-11am). We will test whether there is a difference between treatments over the time period.
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) (stages 2 and 3) and REM sleep.
大体时间:14th night after treatment starts.
|
High-density EEG, spectral power for frequency ranges low-delta: 0.5-1 Hz; delta: 1-4.5 Hz; theta: 4.5-8Hz; alpha: 8-12Hz; sigma: 12-15 Hz; beta: 15-25 Hz; gamma: 25-40 Hz. Absolute Electroencephalographic (EEG) Power During Non-Rapid Eye Movement (NREM) and REM sleep (12 statistical comparisons). Unit of measurement is μV^2. |
14th night after treatment starts.
|
合作者和调查者
调查人员
- 首席研究员:Camilla Hoyos, MPH, PhD、Woolcock Institute of Medical Research
- 首席研究员:Brendon Yee, MBChB, FRACP, FCCP, PhD、Woolcock Institute of Medical Research
研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (估计的)
研究完成 (估计的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (实际的)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 16837
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)?
IPD 计划说明
Non-identifiable IPD will be shared upon reasonable request to the Principal Investigators.
IPD 共享时间框架
Non-identifiable IPD will become available one year after the Actual Study Completion Date and will be available for ten years.
IPD 共享访问标准
A copy of the non-identifiable dataset may be requested by academic collaborators not affiliated with the WIMR through a data request form which outlines the investigators, aims and hypotheses, data to be included, a statistical analysis plan, ethics approval, and security measures. Contact the Coordinating Principal Investigator for access to data.
IPD 共享支持信息类型
- 研究方案
- 树液
- 国际碳纤维联合会
- 分析代码
药物和器械信息、研究文件
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研究美国 FDA 监管的设备产品
在美国制造并从美国出口的产品
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