Pilot Study on the Efficacy of Pascoflair in an Acute Stressful Situation (TSST)

Study Overview
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Brief Summary
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A randomized, double blind, placebo-controlled pilot study on the efficacy of Passiflora incarnata L. in an acute stressful situation

Detailed Description
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Randomized, double-blind, placebo-controlled, single-center study During Visit 1 study information and an informed consent form are handed out. After study inclusion on Visit 2, participants are assigned to one of two groups at random and receive the test products (either Pascoflair® or placebo tablets). The 3rd visit includes the completion of questionnaires regarding wellbeing and the Trier Social Stress Test.

Official Title
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A Randomized, Double Blind, Placebo-controlled Pilot Study on the Efficacy of Passiflora Incarnata L. in an Acute Stressful Situation

Conditions
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Healthy, Stress

Intervention / Treatment
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* Drug: Passiflora incarnata
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Provide written informed consent; Healthy male and female subjects Non-smoker; Age 25 to 45 years; BMI ≥ 19 to ≤ 30 kg/m2 Exclusion Criteria: Any known allergies to the test substance; Any known addiction to drugs, alcohol or positive results in the drug screening test; Any serious general illness, ongoing or within the last 12 months; Any febrile illness (> 24 hrs.) within 7 days prior to treatment; Any antibiotics for the last four weeks before study inclusion; Diabetes mellitus; Known heart disease, hypertension, kidney disease, significant respiratory disease, epilepsy, or rheumatoid arthritis; Known immunologic or infectious disease (e.g. hepatitis, tuberculosis, HIV or AIDS) which could place the subject at risk or interfere with the accuracy of the study results; Pregnancy or lactating; Current participation or participation in any type of clinical study in the past week; Current or past participation in a TSST study; Employees of the Sponsor or the CRO; Any other medication that, in the opinion of the Investigator is likely to affect their response to treatment; Clinically relevant abnormalities in physical examinations, vital signs, clinical chemistry, or haematology as judged by the Investigator; Any other condition the Investigator or their duly assigned representatives believes may affect the ability of the individual to complete the study or the interpretation of the study results.

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 45 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
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Placebo arm | Drug: Placebo<br>* 3 x 1 ablet per day for 3 days<br>|
| Active Comparator: Verum<br>Verum arm - Pascoflair 425mg | Drug: Passiflora incarnata<br>* 3 x 1 tablet per day for 3 days<br>* Other names: Pascoflair 425mg coated tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VAS Insecurity (During) | The primary objective is to assess effects of P. incarnata on psychological stress measured by Visual Analogue Scales (VAS; Bond and Lader 1974) by comparing scores collected before, during and after stress exposure between the P. incarnata and a placebo group. In this study, psychological stress is defined as stress perception, anxiety and insecurity. These three variables are determined simultaneously in the study before, during and after the stress test. Minimum = 0 mm; Maximum = 100 mm, higher value = represent a worsend outcome. | during stress test = Visite 3 | 
| VAS Anxiety (During) | The primary objective is to assess effects of P. incarnata on psychological stress measured by Visual Analogue Scales (VAS; Bond and Lader 1974) by comparing scores collected before, during and after stress exposure between the P. incarnata and a placebo group. In this study, psychological stress is defined as stress perception, anxiety and insecurity. These three variables are determined simultaneously in the study before, during and after the stress test. Minimum = 0 mm; Maximum = 100 mm, higher value = represent a worsend outcome. | during stress test = Visite 3 | 
| VAS Stress Perception (During) | The primary objective is to assess effects of P. incarnata on psychological stress measured by Visual Analogue Scales (VAS; Bond and Lader 1974) by comparing scores collected before, during and after stress exposure between the P. incarnata and a placebo group. In this study, psychological stress is defined as stress perception, anxiety and insecurity. These three variables are determined simultaneously in the study before, during and after the stress test. Minimum = 0 mm; Maximum = 100 mm, higher value = represent a worsend outcome. | during stress test = Visite 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Cortisol (Pre-post Comparison) | 2 min. prior to and 1 min. after the TSST | 1 day | 
| ACTH (Pre-post Comparison) | ACTH - Adrenocorticotropes Hormon - 2 min. prior to and 1 min. after the TSST | 1 day | 
| Epinephrine (Before) | 2 min. prior the TSST | 1 day | 
| Norepinephrine (Before) | 2 min. prior the TSST | before stress test | 
| State Anxiety (STAI-X1) Questionnaire | The STAI-X1 measures state anxiety (one scale). Answers are given on a four-point rating scale ranging from 1 = not at all to 4 = very true. The questionnaire is used as baseline measurement at V2. In addition, it is also employed before and immediately after the stress test at V3 to assess changes in state anxiety. Assess V2, before and after V3 | 1 day | 
| POMS Questionnaire | The POMS assesses the four states depression/anxiety, fatigue, vigor and hostility (4 scales). High vigor scores reflect a positive mood whereas high scores in the other subscales indicate negative mood. Subjects rate their mood state on a 7-point rating scale ranging from 1 = not at all to 7 = very strongly. The questionnaire is completed on V2 and V3. | 1 day | 
| MDBF Questionnaire | The MDBF assesses the three bipolar dimensions good/bad mood, wakefulness/tiredness and calmness/agitation (3 scales). The short form of the MDBF and its parallel version (versions A and B) each consist of 12 items. Subjects rate their mood state on a 5-point rating scale ranging from 1 = not at all to 5 = very true. To determine mood changes induced by the TSST, the questionnaire is completed shortly before (version A) and immediately after the TSST (version B). Assess before and after V3 | 1 day | 
| LSEQ Questionnaire (Getting to Sleep-Falling Asleep Easier Than Usual) - Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Getting to Sleep-Falling Asleep More Quickly Than Usual] - Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Getting to Sleep-Feeling More Drowsy Than Usual] - Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; lower values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Quality of Sleep - More Restful Than Usual] - Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Quality of Sleep - Fewer Periods of Wakefulness Than Usual] Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2, visite 3 | 
| LSEQ Questionnaire (Awakening From Sleep- Easier Than Usual] Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Awakening From Sleep- Quicker Than Usual] Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Behavior Following Awakening- Feeling Alert Upon Awakening] Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Behavior Following Awakening- Feeling Alert Now] Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; higher values represent a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| LSEQ Questionnaire (Behavior Following Awakening- Less Clumsy Balance and Coordination Upon Getting-up] Changes From V2 to V3 | The LSEQ investigates four aspects of sleep using VAS: getting to sleep, quality of sleep, awakening from sleep and behavior following awakening. The LSEQ is completed on V2 and V3. V2 = For each female, V2 is scheduled to take place on day 6 (-8) after the last contraceptive intake of a menstrual cycle. Upon arrival, subjects meeting all inclusion and no exclusion criteria are admitted to study participation and receive a random number starting from R001. V3 = After 2 days of treatment, the final appointment takes place in the afternoon. For each female, the appointment for V3 will be scheduled to take place on day 9 (-11) after the last contraceptive intake of a menstrual cycle. Females will be asked if oral contraceptives were administered on a regular basis and if pregnancy can be excluded. The LSEQ is a VAS scale 0 - 100mm, the value below is Change in percent; a higher value is a better outcome. | Visite 2 (before treatment), Visite 3 (after treatment) | 
| Norepinephrine (After) | 2 min. after the TSST, higher value is better | 1 day | 
| Sympathovagal Balance (Before TSST, Sitting - 1. Measurement) | Sympathovagal balance is a measure of heart rate variability and gives information about the autonomic state that is regulated by sympathetic and parasympathetic influences. The low frequency component reflects sympathic activity, whereas the high requency domain gives Information about the parasympatic activity. Higher scores indicate a higher activation of the sympathic nervous System. | before TSST | 
| Sympathovagal Balance (Before TSST, Standing - 2. Measurement) | Sympathovagal balance is a measure of heart rate variability and gives information about the autonomic state that is regulated by sympathetic and parasympathetic influences. The low frequency component reflects sympathic activity, whereas the high requency domain gives Information about the parasympatic activity. Higher scores indicate a higher activation of the sympathic nervous System. | before TSST | 
| Sympathovagal Balance (During TSST, Preparation - 3. Measurement) | Sympathovagal balance is a measure of heart rate variability and gives information about the autonomic state that is regulated by sympathetic and parasympathetic influences. The low frequency component reflects sympathic activity, whereas the high requency domain gives Information about the parasympatic activity. Higher scores indicate a higher activation of the sympathic nervous System. | during TSST | 
| Sympathovagal Balance (During TSST, Interview - 4. Measurement) | Sympathovagal balance is a measure of heart rate variability and gives information about the autonomic state that is regulated by sympathetic and parasympathetic influences. The low frequency component reflects sympathic activity, whereas the high requency domain gives Information about the parasympatic activity. Higher scores indicate a higher activation of the sympathic nervous System. | during TSST | 
| Sympathovagal Balance (During TSST, Arithmetics - 5. Measurement) | Sympathovagal balance is a measure of heart rate variability and gives information about the autonomic state that is regulated by sympathetic and parasympathetic influences. The low frequency component reflects sympathic activity, whereas the high requency domain gives Information about the parasympatic activity. Higher scores indicate a higher activation of the sympathic nervous System. | during TSST | 
| Sympathovagal Balance (After TSST, Standing - 6. Measurement) | Sympathovagal balance is a measure of heart rate variability and gives information about the autonomic state that is regulated by sympathetic and parasympathetic influences. The low frequency component reflects sympathic activity, whereas the high requency domain gives Information about the parasympatic activity. Higher scores indicate a higher activation of the sympathic nervous System. | after TSST | 
| Sympathovagal Balance (After TSST, Sitting - 7. Measurement) | Sympathovagal balance is a measure of heart rate variability and gives information about the autonomic state that is regulated by sympathetic and parasympathetic influences. The low frequency component reflects sympathic activity, whereas the high requency domain gives Information about the parasympatic activity. Higher scores indicate a higher activation of the sympathic nervous System. | after TSST | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tsst, Pascoflair, passiflora incarnata, non smoking male, and female volunteers