Influence of Luteolin on Memory in Healthy Subjects

Study Overview
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Brief Summary
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Proof of concept study on physiological processes (forgetting and memory functions, attention, working memory) in participants after multiple administration of the dietary supplement Luteolin.

Detailed Description
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In the experimental phase the investigator will administer 500 mg Luteolin (2x250 mg capsules) per day formulated for oral administration for 7.5 days (first intake: visit 1/3 in the morning; last intake: visit 2/4 in the morning). The last intake on visits 2 resp. 4 is important as the participants then have to recall the learned material from visits 1 resp. 3 during a steady-state status of Luteolin. Subjects will be randomly allocated to treatment groups (starting with investigational product or placebo). Identity of Investigational Product: Luteolin extracted from Chrysanthemum Ramat 98% HPLC by Scyherb® food grade certified according to Safe Quality Foods (SQF) - Level 3 Comprehensive Food Safety and Quality Management System Certification by the Safe Quality Food Institute (SQFI). Control intervention consists of identical looking placebo capsules containing mannitol formulated for oral administration to be taken twice daily (e.g. every morning and evening) for 7.5 days (first intake: visit 1/3 in the morning; last intake: visit 2/4 in the morning) with water.

Official Title
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Influence of the Dietary Supplement Luteolin on Memory in Healthy Subjects

Conditions
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Memory

Intervention / Treatment
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* Dietary Supplement: Luteolin
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: male or female healthy normotensive (BP between 90/60mmHg and 140/90mmHg) BMI <30 kg/m2 aged between 18 and 40 years native or fluent German-speaking able and willing to give written informed consent as documented by signature and comply with the requirements of the study protocol Exclusion Criteria: Bodyweight <50 kg acute or chronic psychiatric disorder (e.g. major depression, psychoses, somatoform disorder, suicidal tendency) concomitant acute or chronic disease state (e.g. renal failure, hepatic dysfunction, cardiovascular disease, acute infections etc.) women who are pregnant or breast feeding intention to become pregnant during the course of the study known or suspected non-compliance, drug or alcohol abuse inability to follow the procedures of the study, e.g. due to language problems, psychological disorders participation in another study with investigational drug within the 30 days preceding and during the present study enrolment of the investigator, his/her family members, employees and other dependent persons participation in one of our previous studies using the same memory tests in the past 2 years Psychoactive drugs and alcoholic beverages 3 days (psychoactive drugs) resp. 12 hours (alcohol) before test visits 1-4.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: randomized double-blind placebo-controlled cross-over counter-balanced
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental intervention<br>In the experimental phase we will administer 500 mg Luteolin (2x250 mg capsules) per day formulated for oral administration for 7.5 days (first intake: visit 1/3 in the morning; last intake: visit 2/4 in the morning). The last intake on visits 2 resp. 4 is important as the participants then have to recall the learned material from visits 1 resp. 3 during a steady-state status of Luteolin. | Dietary Supplement: Luteolin<br>* Luteolin extracted from Chrysanthemum Ramat 98% HPLC by Scyherb® food grade certified according to Safe Quality Foods (SQF) - Level 3 Comprehensive Food Safety and Quality Management System Certification by the Safe Quality Food Institute (SQFI).<br>|
| Placebo Comparator: Control Intervention<br>Control intervention consists of identical looking placebo capsules containing mannitol formulated for oral administration to be taken twice daily (e.g. every morning and evening) for 7.5 days (first intake: visit 1/3 in the morning; last intake: visit 2/4 in the morning) with water. | Other: Placebo<br>* mannitol formulated for oral administration (capsules)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Visual Memory Test | Performance in a visual memory test (Rey-Osterrieth complex figure test (Rey 1941) and (Osterrieth 1944)). As parallel version the modified complex Taylor figure test (Hubley 2002). Participants will have to copy the complex figure of Rey Osterrieth. After 3 and 20 minutes delay the subject will be asked to draw the figure from memory. 7 days after learning there will be a delayed recall. Performance is calculated by scoring for accuracy and relative position of the 18 units in the whole of the design. Maximal score is 36 points. | after 3 minutes, short delay (20 minutes), long delay (7 days): to assess differences between these time points | 
| Verbal Memory Task | Verbal memory task (de Quervain, Roozendaal et al. 2000). A parallel version will be used for the second study phase. Subjects will view series of 60 unrelated German nouns each presented for 4 s on a computer screen with the explicit instruction to learn them for immediate and delayed recall. For the free-recall test, subjects will be asked to write down all the words they remember. The number of correctly recalled words (hits) will be the relevant output. Delayed recall of all 60 words will be tested about 15 min (short delay) and 7 days (long delay, after treatment phase) after presentation. | immediate recall, short delay (15 minutes), long delay (7 days): to assess differences between these time points | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Digit Span Task | Performance in a Working memory test assessed by the digit span task, a subtest of the WIE (von Aster 2006). A parallel version will be used for each visit. Each correct reproduction of a sequence of numbers is scored with one point. | after each treatment phase (duration one week) on vists 2 and 4 | 
| Mode state (MDBF) | Mood state will be assessed for the past treatment phases of one week (visit 2 and 4) with the self-rating instrument MDBF (Steyer 1997) consisting of 12 items to be rated in a 5 scale mode. The total score is calculated by summing the answers in each of the 3 dimensions good/bad mood, alertness/sleepiness, rest /restlessness with 4 items in each dimension. We will use Version A and Version B. | after each treatment phase (duration one week) on vists 2 and 4 | 
| Depressive symptoms | Depressive symptoms will be assessed with the self-rating questionnaire MADRS-S (Schmidtke 1988) for the past week (treatment phases). This scale consists of 9 items assessing participants' mood, feelings of unease, sleep, appetite, ability to concentrate, initiative, emotional involvement, pessimism and zest for life. Each item is scored between 0 and 3. The total score is calculated by summing the answers of the nine items, ranging between 0 and 27 (higher scores indicate increased impairment). | after each treatment phase (duration one week) on vists 2 and 4 | 
| Anxiety | Anxiety will be measured for the past treatment phases with the self-rating instrument STAI-G form X1 (state) (Laux 1981).This instrument consists of 20 items scored between 1-4. The total score is calculated by summing the answers, ranging between 20 and 80. | after each treatment phase (duration one week) on vists 2 and 4 | 
| Visual Analog Scales Subjective Memory Function | Respondents specify their level of agreement to the statement by indicating a position along a continuous line (10 cm) between the two end-points: better memory function respectively than normal or worse. The score ranges between -5 and + 5. | after each treatment phase (duration one week) on vists 2 and 4 | 
| Visual Analog Scales Quality of Sleep | Respondents specify their level of agreement to the statement by indicating a position along a continuous line (10 cm) between the two end-points: better sleep quality respectively than normal or worse. The score ranges between -5 and + 5. | after each treatment phase (duration one week) on vists 2 and 4 |