Evaluation of a Combination of Plants in Anxiety-related Sleep Disorders: Randomized Trial Versus Placebo

Study Overview
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Brief Summary
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The objective of this double-blind randomized clinical trial is to compare the effects of a dietary supplement based on eschscholtzia and valerian extracts to a placebo after 28 days of supplementation, in subjects suffering from sleep troubles associated with anxiety.

Official Title
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Evaluation of a Combination of Plants in Anxiety-related Sleep Disorders: Randomized Trial Versus Placebo

Conditions
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Sleep Troubles Associated With Anxiety

Intervention / Treatment
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* Dietary Supplement: Noctesia
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Woman or man, aged of 18 to 65 years; In good general health as evidenced by medical history and physical examination; Having at least 3 episodes of sleep disorders per week including one or more of the following: difficulty falling asleep or difficulty staying asleep or poor quality sleep Waking up earlier than desired The insufficient sleep duration and quality is coupled with a feeling of general fatigue; Sleep disorder last for more than 1 month; Presenting moderate to severe sleep disorder in the past month (ISI ≥ 15); With anxiety resulting in a HAM-A score > 8 and < 25; For women of childbearing age (women of childbearing potential, pre-menopausal or having postmenopausal amenorrhea of less than 12 months, and women who have not undergone surgical sterilization): Negative blood pregnancy test Acceptance to use an effective method of contraception, established for at least 1 month, and throughout the duration of the study; Fluent French speaking; Provision of signed and dated informed consent form; Stated willingness to comply with all study procedures and availability for the duration of the study. Exclusion Criteria: A score > 10 on the ESS scale (that would correspond to serious hypersomnia); Sleep disorders secondary to another health problem (sleep apnea syndrome, narcolepsy-cataplexy, idiopathic hypersomnia, restless legs syndrome, chronic pain syndrome, ...) or an environmental factor (noise, light ...) or socio-professional (shift work, young child at home, people who are often jet lagged,… ); Severe psychiatric disorder or disease within 6 months before inclusion (depression, bipolar disorder, severe anxiety, psychosis, schizophrenic disorders, dementia,…) or a severe neurologic trouble (Alzheimer's, autism, Parkinson's disease, …); Subjects presenting severe gastro-intestinal, hepatic, respiratory, kidney or cardiovascular disorder or severe infection (e.g. HIV, hepatitis, …); Acute or chronic somatic pathologies which can interfere with sleep: kidney cancer, etc.; Subjects with pre-menstrual syndrome or myasthenia gravis; Subjects who drink more than 2 glasses of alcohol per day (> 20g of alcohol per day) or with exaggerated consumption of theine (≥ 1l per day) and caffeine-rich (≥ 800ml per day) beverages and energy drink (≥ 330ml per day); Smoker; Subject consuming drugs and/or with historical drug addiction; Under psychotropic treatment within the last month before screening (neuroleptic, anxiolytic, antidepressant, hypnotic, sedative, …) or under current medication treatment which may alter the waking state (for example: cortisone, dopamine, amphetamine, antihistamines, beta-blockers, certain cough syrups, .…); Volunteer with suicidal risk according to the investigator; Under phytotherapy treatment or food supplement for sleep disorders within the last month before screening; Volunteer presenting current infection and/or fever; Volunteer with medical history of stroke or head trauma; Pregnant or lactating woman; Known allergy or intolerance to one product component (valerian, eschscholtzia or excipients); Subjects having participated to another clinical trial (with an investigational product) one month before the inclusion; Subjects that present alterations of their cognitive functions that will interfere with the comprehension of the study and procedures and/or with the completion of questionnaires; Vulnerable patient (deprived of liberty by judicial or administrative decision, under guardianship, curatorship or safeguard of justice, …); Pharmacological resistance to common hypnotic/sedative drugs; Allergy/intolerance to the actimeter straps; Recent (< 1 month before the inclusion) change in lifestyle (food, body weight > 5kg, sport).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Group (A)<br>120 mg of eschscholtzia extract and 50 mg of valerian extract by tablet, without support 28 days | Dietary Supplement: Noctesia<br>* 3 tablets every day at bedtime with a large glass of water<br>|
| Placebo Comparator: Group (B)<br>Placebo 28 days | Dietary Supplement: Placebo<br>* 3 tablets every day at bedtime with a large glass of water<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep disorder severity | Change from baseline of Insomnia Severity Index (ISI) score | Baseline and D28 (end of supplementation) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sleep disorder severity over time | Change from baseline of Insomnia Severity Index (ISI) score | Baseline and D49 (end of follow-up) | 
| Investigator assessment of sleep disorder symptoms severity | Change from baseline of Clinical Global Impression Severity (CGI-S) score | Baseline and D28 (end of supplementation) | 
| Investigator assessment of sleep disorder symptoms improvement | Change from baseline of Clinical Global Impression Improvement (CGI-I) score | Baseline and D28 (end of supplementation) | 
| Patient assessment of sleep disorder symptoms improvement after intervention | Change from baseline of Patient Global Impression Improvement (PGI-I) score | Baseline and D28 (end of supplementation) | 
| Anxiety status | Change from baseline of Hamilton anxiety rating scale (HAM-A) score | Baseline and D28 (end of supplementation) | 
| Anxiety status over time | Change from baseline of Hamilton anxiety rating scale (HAM-A) score | Baseline and D49 (end of follow-up) | 
| Short-form 36 questionnaire (SF36) | Change from baseline of SF36 scores | Baseline and D28 (end of supplementation) | 
| Actimeters | Change from baseline of the mean values obtained from actimeters recording during the 7 days | Baseline, D7, D14, D21 and D28 (end of supplementation) | 
| Electronic sleep diaries | Change from baseline of the mean values obtained from electronic sleep diaries during the 7 days | Baseline, D7, D14, D21 and D28 (end of supplementation) | 
| Evolution of sleep troubles | Change from baseline of sleep troubles regarding changes in medical prescriptions, reason of changes and number of intercurrent medical visits for sleep disorders | Baseline, D28 (end of supplementation) and D49 (end of follow-up) | 
| Addiction | Change from baseline of Addiction questionnaire scores | Baseline and D49 (end of follow-up) | 
| Adverse events | Incidence of adverse events | Baseline D7, D14, D21, D28 (end of supplementation) and D49 (end of follow-up) |