Sleep Well Observation Study

Study Overview
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Brief Summary
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Insomnia is characterized by the recurring difficulty to fall or remain asleep despite motivation and means to do so. People with insomnia also experience excessive daytime sleepiness and other cognitive impairments while they are awake. Facing the situation mentioned and realizing that especially early preventive measures are needed to fight the increasing costs for treatment of sleep related diseases, effective nutrients might be a good and safe option to improve sleep quality.This single-arm, open-label, prospective, observational exploratory pilot study aims at collecting first data on efficacy and safety of Sleep Well.

Detailed Description
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This single-center study is a one-armed, open-label, prospective, observational exploratory pilot study and has a duration of 17 days per participant. A total of 50 healthy participants (n=25 female, n=25 male) aged 18-50 years inclusive reported sleep problems at a preliminary stage to the criteria of the German S3 guideline non-restorative sleep/sleep disorders - insomnia in adults for the definition of non-organic insomnia according to ICD-10 (F 51.0) are included into the study. The total study population of N=50 will include two groups: A subgroup of n=40 will not undergo polysomnographic assessment (nonPSG), a group of n=10 will undergo polysomnographic assessment (PSG), in addition to all other assessments. The nonPSG group has a total of 3 study centre visits (V1, V2, V3) and and the PSG group has two further visits prior to V2 and V3 resulting in five study centre visits (V1, V2-1, V2, V3-1, V3). Except for the PSG, all other assessments are identical in the two groups. All included individuals will take one Sleep Well sachet daily over an intake period of 14 days with an acute dosage at two visits.

Official Title
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The Sleep Well Observation Study: a Single-arm, Open-label, Prospective Intra-individual Change Controlled, Exploratory Pilot Study

Conditions
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Sleep Disturbance

Intervention / Treatment
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* Dietary Supplement: Sleep Well Sachet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: • Voluntary, written, informed consent to participate in the study. Male or female aged between 18-50 years (inclusive). Self reported sleep problems precursing the criteria of the German S3 guideline non-restorative sleep/sleep disorders - insomnia in adults. Habitual bedtime between 9 pm and midnight. Agreement to avoid foods such as pitted fruit, bananas and chocolate 24 hours before saliva sample collection. Willing to download wearable app. Easy access to internet for daily e-diary. Cooling capacities available for storage of saliva samples Exclusion Criteria: • Body mass index (BMI) <18.0 or >30.0 kg/m2. Women who are currently pregnant or breastfeeding. Any known history of a disorder affecting sleep quality, such as narcolepsy, obstructive sleep apnea (OSA), restless leg syndrome (RLS), periodic limb movement syndrome (PLMS) or any organic caused sleep disorders e.g. benign prostatic hyperplasia (BPH), renal insufficiency, hepatopathy, urinary tract infections, irritated bladder, or any psychiatric disorder, e.g. depression, anxiety. 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). Previous (last 4 weeks prior to screening) or current intake of drugs that could influence sleep patterns including hormone therapy, health products and oriental herbs. Binge drinking (males >140 g/week, females >70 g/week), heavy smoking (>10 cigarettes/day), high caffeine intake (>10 glasses/day). Self-declared illicit drug use (including cannabis and cocaine) for 3 months prior to screening and during the intervention period. Have a high blood pressure (systolic over 159 mmHg or diastolic over 99 mmHg). Have learning and/or behavioural difficulties such as dyslexia or attention deficit hyperactivity disorder (ADHD). Have a visual impairment that cannot be corrected with glasses or contact lenses (including colour-blindness). History or planned travel to a different time zone within 1 month of the first visit or/and during the study participation. Not fluent in German. Have relevant food allergies/intolerances/sensitivities to any substance in the study product. Have oral disease. Participation in another study with any investigational product within 30 days of screening and during the intervention period. Investigator believes that the participant may be uncooperative and/or noncompliant and should therefore not participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sleep Well Sachet Treatment<br>Sachet of Sleep Well direct granulate (2.0 g) 1 sachet contains: 190 mg standardized dry extract of Melissa officinalis leaf , 75 mg dried pressed juice of fresh Lactuca sativa herb, 0.41 g Magnesiumdicitrate, 0.12 g L-Tryptophan, excipients and natural flavors. | Dietary Supplement: Sleep Well Sachet<br>* Individuals will take 1 Sleep Well sachet daily over 2 weeks Exception: Two sachets are taken on days 4 and 17 upon acute assessment<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in perceived sleep quantity/quality | Measured as per daily electronic sleep diary entries at home. Comparing pre vs. post intervention assessment. | 2 weeks intervention | 
| Change in perceived sleep quantity/quality | Measured as per daily electronic sleep diary entries at home. Comparing pre vs. post intervention assessment. | 1 day intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in perceived sleep quantity/quality summarized retrospectively | Method: standardized sleep questionnaire SF-B/R. Comparing pre vs. post intervention assessment on site. | 2 weeks | 
| Change in daytime sleepiness | Pre vs. Post intervention assessment of daytime sleepiness measured with the ESS (Epworth Daytime sleepiness scale) questionnaire | 2 weeks | 
| Change in state anxiety | Pre vs. Post intervention assessment of experienced anxiety symptoms via the STAI-X1 questionnaire | 1 day intervention and 2 weeks | 
| Change in negative emotional state | Pre vs. Post intervention assessment of anxiety depression and stress symptoms measured via the DASS-21 questionnaire | 2 weeks | 
| Change in quality of life | Pre vs. Post intervention assessment of life quality via the WHO-QOL-BREF questionnaire | 2 weeks | 
| Change in domain specific cognitive performance | Pre- vs. Post intervention assessment of domain specific cognitive performance via the COMPASS battery such as attention and vigilance, working memory, spatial memory, memory, executive functions | 1 day and 2 weeks | 
| Change in biomarker for chronic stress | Change in biomarker for chronic stress via the salivary evening cortisol level taken at 8 pm on two days pre-intervention and 2 days post intervention | 2 weeks | 
| Change in biomarker for sleep readiness | Change in biomarker for sleep readiness via the salivary evening melatonin level taken at 8 pm on two days pre intervention and two days post intervention. | 2 weeks | 
| Change in biomarker for chronic stress via CAR | Change in biomarker for chronic stress via CAR (measured immediately at awakening, +30 min and +45 min thereafter) determined as area under the curve (AUC) and increase in biosamples taken on two days pre intervention and two days post intervention. | 2 weeks | 
| Change in PSG-recorded sleep quantity/quality | Pre vs. Post intervention assessment as measured by the polysomnographic PSG assessment using a home portable device | 1 day intervention and 2 weeks | 
| Tolerability of the investigational product in view of subject | Tolerability of the product as per the self-declaration of the subject - safety assessment | 1 day and 2 weeks | 
| Adverse events | Frequency and kind of adverse events/medical events during the course of the study - safety assessment | 1 day and 2 weeks | 
| Change in physiological sleep quantity/quality | Measured by actigraphy (wearable). Comparing pre vs. post intervention assessment as Minutes Asleep (minutes spent in deep, rapid-eye-movement (REM), light or asleep stages), Minutes Awake (number of minutes spent in wake or awake stages), Minutes to fall asleep (number of minutes it took to fall asleep), Time in Bed (number of minutes spent in bed (minutes after wakeup + minutes asleep + minutes awake + minutes to fall asleep)) | 1 day and 2 weeks intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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sleep, herbal supplement, pilot trial