Efficacy and Safety of Eschscholzia Tablets in Adults With Insomnia Disorder Symptoms: A Monocentric, Randomized, Double-blind, Placebo-controlled, Parallel Group, Prospective Study
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- A. Vogel AG
- 入组人数
- 104
- 试验地点
- 1
- 主要终点
- Change in perceived sleep quality over time during the treatment period, as assessed by the longitudinal profile of the change from baseline in ISI total score values at each post-baseline assessment time point
研究概览
简要总结
This is a clinical study aimed at evaluating the efficacy and safety of Eschscholzia tablets in adults with insomnia disorder symptoms. The study will be conducted at one center, participants will randomly be assigned to either the treatment or placebo. Neither the participants, nor the researchers will know who is receiving the treatment (double-blind). The study is also placebo-controlled, meaning some participants receive a dummy pill instead of the actual treatment, and it involves a parallel-group design, where the treatment and placebo groups are studied at the same time. The study is exploratory, meaning it is investigating new possibilities and is not yet fully conclusive.
The purpose of this study is to determine main efficacy and safety of the newly developed herbal medicinal product Eschscholzia tablets. A total of 100 subjects will be enrolled in the study and assigned to either Eschscholzia tablets or placebo.
The Local Ethics Committee at the clinical site has given their approval for the study to be run.
Male or female participats aged between 18 and 75 years (inclusive), generally healthy and with a self reported history of disturbed sleep on at least 3 nights per week for at least the prior 1 month with a self-reported impact on daytime functioning are allowed to take part in the study.
Overall, the study has the following visits in the clinic, planned for each patient: Screening visit, Study centre Visit 2, Final study centre Visit 3. Between these visits participants will go through a "run-in" period (1 week between Visit 1 and 2) and treatment period (1 month between visit 1 and 3), both at home. Upon visit 2 participants will obtain the study product. They will be asked to administer a daily dose of 2 tablets (either Eschscholzia tablets or Placebo) over a 4-week period, starting from Visit 2 and continuing until Visit 3. Every intake of study product should be noted on the sleep diary pages that the participants obtain.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Voluntary, written, informed consent to participate in the study
- •Self reported difficulty or maintaining sleep or waking too early, or daytime impairement or distress based on subject's information related to sleep pattern during at least the preceding month before screening.
- •Self reported history of disturbed sleep on at least 3 nights per week for at least the last 1 month before screening.
- •≥30 min to fall asleep
- •≥30 min awake during sleep time
- •Self-reported total sleep time of ≤ 6.5 h
- •ISI total score ≥ 10
- •Confirmation of presence of insomnia diagnosis according to the ICD-10 F51.0/ICD-11 7A00 criteria by the physician upon anamnesis.
- •Reported Impact on daytime functioning associated with sleep maintenance as measured with question 7 of the ISI, Score >= 2
- •Freezing capacities available for storage of saliva samples.
- •Willingness and infrastructure available to run aktigraphic device (bed sensor) properly
排除标准
- •Body mass index (BMI) <18.0 or >30.0 kg/m
- •Individual is pregnant, planning to be pregnant during the study period, lactating, or women of childbearing potential who are unwilling to commit to the use of a medically approved form of contraception throughout the study period.
- •Any known acute organic disorder affecting sleep quality, such as narcolepsy, obstructive sleep apnea (OSA), restless leg syndrome (RLS), periodic limb movement syndrome (PLMS), circadian rhythm disorder, rapid-eye-movement behavior disorder, benign prostatic hyperplasia (BPH), urinary tract infections, irritated bladder, acute and/or chronic pain.
- •Any known acute or chronic psychiatric condition (e.g., severe mono- or bipolar depression, history of suicidal ideation or attempt, severe anxiety disorders, severe personality disorders, borderline personality disorder, psychoses).
- •Have a significant acute or chronic coexisting illness or any condition which contraindicates entry to the study in the opinion of the Investigator (e.g. migraines, active infections, renal insufficiency, hepatopathy, and dementia).
- •History of alcohol or drug misuse
- •Regular alcohol consumption exceeding 140g/week, heavy smoking (>10 cigarettes/day), high caffeine intake (>10 glasses/day).
- •Current intake of drugs that could influence sleep (e.g., psychotropic, sedatives, hypnotics, nicotine-replacement therapies, over-the-counter sleep aids, hormone therapy, health products and oriental herbs (such as valerian, hops, passionflower, hypericum).
- •Have a clinically significant high/low blood pressure (systolic over 159 mmHg, resp. lower than 80 mmHg or diastolic over 99 mmHg, resp. lower than 60 mmHg).
- •History or planned travel to a different time zone within 1 month of the first visit or/and during the study participation.
- •Shift-worker.
- •Not fluent in local language.
- •Have (known) hypersensitivity to plants from the poppy family (Papaveraceae) or known hypersensitivity to the active substance/s (Eschscholzia californica, microcrystalline cellulose, Colloidal anhydrous silica, sodium croscarmellose, glycerol distearate, caramel couleur and Ferrous(III) oxide).
- •Participation in another study with any investigational product within 30 days of screening and during the intervention period.
- •Investigator believes that the subject may be uncooperative and/or noncompliant and should therefore not participate in the study.
研究组 & 干预措施
Verum Group: Eschscholzia tablets
One Escholzia tablet (1.0 g) contains as active pharmaceutical ingredient:
0.503 g Eschscholzia californica Herba rec. tinct. conc. as the active pharmaceutical ingredient (API) corresponding 600 mg powdered herbal material.
干预措施: Eschscholzia tablets (Drug)
Control Group: Placebo tablets
A placebo tablet will be provided that matches the verum in its optical and sensorial properties and posology. Contains: microcrystalline cellulose, Colloidal anhydrous silica, glycerol distearate, caramel couleur and colorants.
干预措施: Placebo Tablets (Drug)
结局指标
主要结局
Change in perceived sleep quality over time during the treatment period, as assessed by the longitudinal profile of the change from baseline in ISI total score values at each post-baseline assessment time point
时间窗: From baseline over the phase of the 4 weeks treatment
Endpoint evaluates changes in perceived sleep quality over time during treatment based on Insomnia Severity Index (ISI) change from baseline at each scheduled post-baseline assessment time point.
Change from baseline over the 4-week treatment phase in perceived sleep quality, as measured by the summed area under the curve (summed up ISI AUC) of the Insomnia Severity Index (ISI) Total Score.
时间窗: Change between baseline and over 4-week treatment phase
Min: 0 score points, Max: 28 score points Lower scores mean better outcomes The global effect of the investigational medicinal product (IMP) on sleep will be evaluated using the area under the curve (AUC) of repeatedly measured subjective insomnia severity, assessed by the ISI Total Score.
Time to reach a clinically relevant insomnia symptom severity reduction of -9 units on the ISI total score scale
时间窗: From baseline over the phase of the 4 weeks treatment
achieves a clinically relevant reduction in insomnia severity, corresponding to a change from baseline of Δ ISI ≤ -9 points
次要结局
- Time to reach a clinically relevant insomnia symptom severity reduction of -9 units on the ISI total score scale(From baseline over the phase of the 4 weeks treatment)
- Subjective efficacy(Day 36)
- Subjective tolerability(On Day 36)
- Acceptance of the treatment(On day 36)
- Rate/kind of adverse events(on day 36)
- Blood pressure(Change between baseline and day 36)
- Blood pulse(Change between baseline and day 36)
- Change in Blood safety parameters(Change between baseline and day 36)
- Rate/kind of comedication(Change between baseline and day 36)
- Treatment compliance(on day 36)
- Change in biomarker for sleep readiness between baseline and over 4-week treatment phase via the salivary evening melatonin level (8 p.m.)(Change from baseline days 6/7 to chronic treatment by days 34/35)
- Change in perceived sleep quality over time during the treatment and post-treatment period, as assessed by ISI AUC values at each intervention time point.(From baseline over the phase of the 4 weeks treatment)
- Change in perceived sleep quality over time during the treatment and post-treatment period, as assessed by raw ISI total score values at each intervention time point(From baseline over the phase of the 4 weeks treatment)
- Change in perceived overall sleep quality over time during the treatment, as assessed by the sleep diary composite score TSQ1(From baseline over the phase of the 4 weeks treatment)
- Change in perceived overall sleep quality over time during the treatment, as assessed by the sleep diary subscores(From baseline over the phase of the 4 weeks treatment)
- ISI Responder criteria assessed at the end of intervention on visit 3(From baseline to the end of treatment after 4 weeks treatment)
- Change between baseline and over 4-week treatment phase in daytime sleepiness symptoms severity as measured with the Epworth Sleepiness Scale (ESS)(From baseline to the end of the treatment after 4 weeks)
- Change between baseline and over 4-week treatment phase in Profile of Mood states as measured with the POMS-2 questionnaire (POMS-2).(Change between baseline and over 4-week treatment phase)
- Change between baseline and over 4-week treatment phase in state anxiety as measured with the State-Trait-Anxiety-Inventory (STAI-Y1 & Y2).(Change between baseline and over 4-week treatment phase)
- Change between baseline and over 4-week treatment phase in anxiety disorders as per the assessment of the clinician on the HAM-A scale (HAM-A).(Change between baseline and over 4-week treatment phase)
- Change between baseline and over 4-week treatment phase in psychological well-being as measured with the Depression, Anxiety, and Stress Scale (DASS-21).(Change between baseline and over 4-week treatment phase)
- Change between baseline and over 4-week treatment phase in physiological sleep quantity and quality and physiological measures via actigraphy (wearable).(Change between baseline and over 4-week treatment phase)
- Change in biomarker for stress between baseline and over 4-week treatment phase via the salivary evening cortisol levels (8 p.m.)(Change from baseline days 6/7 to chronic treatment after days 34/35)
- Change between baseline and over 4-week treatment phase in ratio of biomarker evening melatonin level/ evening cortisol level (8 p.m.)(Change from baseline days 6/7 to chronic treatment by days 34/35)
- Change between baseline and over 4-week treatment phase in biomarker for chronic stress via the CAR determined(Change from baseline days 6/7 to chronic treatment by days 34/35)