ACUTE AND CHRONIC EFFECTS OF A BOTANICAL EXTRACT ON ANXIETY, PERCEIVED STRESS, MOOD AND CORTISOL IN HEALTHY ADULTS

Study Overview
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Brief Summary
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Mood disorders, including depression and anxiety, are one of the main causes of the overall disease burden worldwide. In recent years, the efficacy of certain botanicals as an alternative solution for depression has been evaluated in a number of clinical trials. However, only few studies looked at the effects of these botanicals on mood in healthy subjects. The aim of the proposed randomised, double-blind, placebo-controlled, parallel groups methodology is to assess the acute and chronic effects of daily supplementation with a proprietary and standardized botanical extract in comparison to placebo in healthy adults aged 18-60 years with self-reported low mood.

Detailed Description
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The chronic effect of the active product on mood, anxiety, perceived stress, quality of life and cortisol secretion & metabolism will be assessed through validated questionnaires and urine collection after 2, 4 and 8 weeks of daily supplementation. The acute effect of the product will be assessed after a single dose and exposure to an acute psychological stressor. Before, during and after the stressor, saliva samples will be collected and subjective levels of anxiety and mood will be measured. In addition, Galvanic Skin Response (GSR) and heart rate (HR) will be measured throughout the stressor session.

Official Title
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ACUTE AND CHRONIC EFFECTS OF A PROPRIETARY BOTANICAL EXTRACT ON ANXIETY, PERCEIVED STRESS, MOOD AND CORTISOL SECRETION AND METABOLISM IN HEALTHY ADULTS: RANDOMIZED, PLACEBO-CONTROLLED, DOUBLE-BLIND CLINICAL TRIAL

Conditions
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Mood Disorders

Intervention / Treatment
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* Dietary Supplement: Proprietary, standardized botanical extract
* Dietary Supplement: Placebo (maltodextrin)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: With non-pathological feelings of anxiety and/ or stress in daily life: Subjects self-reporting low mood; Total score ≥ 40 at the Profile of Mood State (POMS 2); Score < 16 at the Generalized Anxiety Disorder 7-item (GAD-7) questionnaire Score ≤ 10 at the Patient Health Questionnaire 9-item (PHQ-9) Not meeting the diagnosis criteria for any mental disorder Body Mass Index (BMI) in the normal range: 18.5 ≥ BMI ≤ 30 kg/ m2 For non-menopausal women: using effective contraception/pregnancy is not physiologically possible. Subject showing no difficulty for salivary sampling Subjects capable of and willing to comply with the protocol and to give their written informed consent Main Exclusion Criteria: Diagnosis of psychological pathology within the previous 3 years Diagnosis of cognitive pathology Anxiolytic or antidepressant treatment, within the previous 3 months Event likely to have impacted the subject's emotional and/ or psychological state within the last 8 weeks or planned during the next 8 weeks Menopausal transition High blood pressure Subjects diagnosed with diabetes, cardiovascular disease, recurrent infectious diseases or chronic inflammatory pathology Usual corticoid treatment/ steroidal anti-inflammatory treatment Unbalanced thyroid disease High physical activity practice Tobacco consumption Subjects consuming any food supplement Excessive alcohol or caffeine use Consumption of recreational drugs Subject currently participating in other clinical or nutrition intervention studies, or has done in the past 4 weeks.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active group<br>Proprietary, standardized botanical extract | Dietary Supplement: Proprietary, standardized botanical extract<br>* 2 capsules/ day providing the proprietary botanical extract as unique active ingredient<br>|
| Placebo Comparator: Placebo group<br>Placebo (maltodextrin) | Dietary Supplement: Placebo (maltodextrin)<br>* 2 capsules/ day providing no active component<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mood state | Variation of the Profile of mood states (POMS-2) total score: TMD (Total Mood Disturbance score). The POMS-2 is a scale which includes six mood subscales: Anger, Confusion, Depression, Fatigue, Tension, and Vigor. Each subscale is scored between 0 and 100. TMD is determined by summing the Negative Mood State subscores and subtracting the Vigor subscore (unique Positive Mood State subscale). For each subscale except Vigor, a lower subscore indicates a better mood state. For the Vigor subscale, a higher subscore indicates a better mood state. A lower POMS-2 TMD indicates a better mood state. | Week 8 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| POMS-2 subscores | Variation of the POMS-2 subscores: Anger, Confusion, Depression, Fatigue, Tension, and Vigor. Each subscale is scored between 0 and 100. For each subscale except Vigor, a lower subscore indicates a better mood state. For the Vigor subscale, a higher subscore indicates a better mood state. | week 2, week 4, week 8 | 
| Anxiety state State-Trait Anxiety Inventory | Variation of the State-Trait Anxiety Inventory (STAI-State) score. Min score: 20; Max score: 80. Higher score corresponds to a higher level of anxiety. | week 2, week 4, week 8 | 
| Anxiety state according to the Hospital Anxiety and Depression Scale | Variation of the anxiety subscore of the Hospital Anxiety and Depression Scale (HADS-A). Min score: 0; Max score: 21. Higher score corresponds to a higher level of anxiety. | week 2, week 4, week 8 | 
| Percentage of responders | A responder is defined as a participant with a statistically significant reduction of the POMS-2 TMD T-score. A lower POMS-2 TMD indicates a better mood state. | week 2, week 4, week 8 | 
| Psychological stress | Variation of the Perceived Stress Scale (PSS-10) score (min score: 0; max score: 40; a higher score corresponds to a lower psychological stress feeling) | week 2, week 4, week 8 | 
| Worry feeling | Variation of the Penn State Worry Questionnaire score (min score: 16; max score: 80; a higher score corresponds to a higher worry feeling) | week 2, week 4, week 8 | 
| Coping response to stress | Variations of the COPE inventory score (min score: 60; max score: 240). A higher score indicates that the subject uses more coping strategies in response to stress. | week 2, week 4, week 8 | 
| Depressive-like state | Variation of the depression subscore of the HADS (HADS-D). HADS-D score is comprised between 0 and 21. A higher HADS-D score indicates a higher level of depression. | week 2, week 4, week 8 | 
| Quality of life score | Variation of the World Health Organisation Quality of Life questionnaire (WHOQOL-BREF) score, comprised between 16 and 80. Higher score indicates higher quality of life. | week 2, week 4, week 8 | 
| Cognitive performances | Variation of the performance on serial subtractions tasks: total and correct responses at serials 3s, 7s and 17s. For Serial 3s: Participants will be instructed to count backwards in threes from a given number, as quickly and accurately as possible. For Serial 7s: same task as for serial 3s but with the serial subtraction of 7. Serial 17s: same task as for serial 3s but with the serial subtraction of 17. | week 2, week 4, week 8 | 
| Cognitive performances | Variation of the performance on the tracking task : speed and accuracy. In this task participants are required to use the mouse to move a cursor to attempt to track an asterisk which follows a random on-screen path. The distance between the target and the cursor is then computed every 100 ms. | week 2, week 4, week 8 | 
| Diurnal cortisol secretion | Variation of cortisone/ cortisol urinary concentrations ratio | week 2, week 4, week 8 | 
| Diurnal cortisol metabolism | Variation of allo-tetrahydrocortisol (THFs)/ tetrahydrocortisone (THE) urinary concentrations ratio | week 2, week 4, week 8 | 
| Biological response to an acute stressor | Incremental area under the curve (iAUC) of the salivary cortisol concentration and alpha-amylase activity | week 2, week 4 & week 8; at 15, 30, 45, 60 & 75 min after exposure to the stressor | 
| Psychological response to an acute stressor assessed through the STAI | Variation of the State-Trait Anxiety Inventory (STAI-State) score. Min score: 20; Max score: 80. Higher score corresponds to a higher level of anxiety. | week 2, week 4 & week 8; 30 and 60 min after exposure to the stressor | 
| Psychological response to an acute stressor assessed on a Visual Analogical Scale | Variation of the perceived stress scores obtained at a Visual Analogical Scale (VAS). Score range: 0-100. Higher score indicates a higher level of anxiety. | week 2, week 4 & week 8; 30 and 60 min after exposure to the stressor | 
| Hemodynamic response to an acute stressor | Maximum increase and incremental area under the curve (iAUC) of the heart rate | week 2, week 4 & week 8; 0 to 15 min after exposure to the stressor | 
| Galvanic Skin Response to the acute stressor | Averaged raw score in microSiemens (µS) during exposure to acute stressor, likely to be comprised between 0.5 µS and 5 µS. A higher GSR indicates a higher stress state. | week 2, week 4 & week 8 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mood, Anxiety, Stress, Dietary supplement, Botanical