Cognitive Effects of Sage in Healthy Humans

Study Overview
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Brief Summary
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Extracts of sage and polyphenols have separately been reported to interact with central nervous system (CNS) mechanisms relevant to cognitive performance but, to date, no trial has combined these interventions. The current study investigates the effects of this combined intervention in N=90 healthy males and females between 30-60 yrs, at 600 mg versus placebo, on cognition and mood over a 29 day period.

Detailed Description
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Improved cognitive performance has been observed in humans following supplementation of sage extracts; including recall and mental arithmetic ability. Aspects of mood have also shown improvements; e.g. increased alertness, calmness and contentedness and reduced mental fatigue. These effects are believed to be underpinned by interactions with cholinergic and GABA pathways. Polyphenols too have shown promise in boosting cognition and mood and interaction with vasodilatory pathways and GABA neurotransmission are purported to be the likely mechanisms involved. Research has yet to investigate if a combination of sage terpenes and polyphenols could be even more efficacious via synergistic interaction.The current study investigates the effects of a 600 mg sage/polyphenol combination on cognition and mood in N=90 healthy male and female participants between the ages of 30-60 yrs acutely; on day 1 of supplementation, and chronically; after 29 days. Cognitive and mood data will also be collected every 7 days in the interim via a mobile phone cognitive task battery.

Official Title
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The Acute and Chronic Cognitive Effects of a Sage Extract: a Randomized, Placebo Controlled Study in Healthy Humans

Conditions
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Cognitive Change, Mood Change

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participants must self-assess themselves as being in good health. Aged 30 to 60 years at the time of giving consent In daytime employment and/or higher education Exclusion Criteria: Have any pre-existing medical condition/illness which will impact taking part in the study NOTE: the explicit exceptions to this are controlled (medicated) arthritis, asthma, hay fever, high cholesterol and reflux-related conditions. There may be other, unforeseen, exceptions and these will be considered on a case-by-case basis; i.e. participants may be allowed to progress to screening if they have a condition/illness which would not interact with the active treatments or impede performance. Are currently taking prescription medications NOTE: the explicit exceptions to this are contraceptive and hormone replacement treatments for female participants where symptoms are stable and treatment will not change during the course of the study, those medications used in the treatment of arthritis, high cholesterol and reflux-related conditions; and those taken 'as needed' in the treatment of asthma and hay fever. As above, there may be other instances of medication use which, where no interaction with the active treatments is likely, participants may be able to progress to screening. Have high blood pressure (systolic over 159 mm Hg or diastolic over 99 mm Hg) Have a Body Mass Index (BMI) outside of the range 18.5-30 kg/m2 Are pregnant, seeking to become pregnant or lactating Have learning and/or behavioural difficulties such as dyslexia or ADHD Have a visual impairment that cannot be corrected with glasses or contact lenses (including colour-blindness) Smoker excessive caffeine intake (>500 mg per day) Have food intolerances/ sensitivities Have taken antibiotics, prebiotics or probiotics (including drinks. Eg. Yakult or Actimel) within the past 8 weeks Have any health condition that would prevent fulfillment of the study requirements (this includes non-diagnosed conditions for which no medication may be taken) Are unable to complete all of the study assessments Are currently participating in other clinical or nutrition intervention studies, or have in the past 4 weeks Has been diagnosed with/ undergoing treatment for alcohol or drug abuse in the last 12 months Have been diagnosed with/ undergoing treatment for a psychiatric disorder in the last 12 months Suffers from frequent migraines that require medication (more than or equal to 1 per month) Sleep disturbances (including night-shift work) and/ or are taking sleep aid medication Any known active infections Does not have a bank account (required for payment) Are non-compliant with regards treatment consumption (see 4.3)

Ages Eligible for Study
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Minimum Age: 30 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
Interventional Model Description: The study will follow a randomised, double-blind, placebo-controlled, parallel groups design.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 600 mg sage/polyphenol combination<br>600 mg of this sage/polyphenol combination will be consumed, via capsule, per day for 29 days. | Dietary Supplement: Cognivia<br>* Cognivia is a trademarked sage/polyphenol combination dietary supplement from Nexira<br>|
| Placebo Comparator: Placebo<br>The same number of aesthetically similar capsules will be consumed per day for 29 days. | Dietary Supplement: Placebo<br>* Placebo control capsules were prepared by Nexira also and are aesthetically identical to the Cognivia capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute change in global cognitive task performance | Changes in executive function, working memory, spatial memory, secondary memory and attention as compared to pre-treatment performance on day 1. All tasks have the same x3 outcome measures; accuracy (% correct), errors (% incorrect) and speed (milliseconds) and the individual task scores will therefore be collapsed into global cognitive domains. | 120 minutes and 240 minutes post dose on day 1 of treatment supplementation | 
| Acute changes in mood; as assessed by the Bond-Lader mood scales | The Bond-Lader mood visual analogue scales will be used at baseline and 120- and 240-minutes post dose on day 1. The derived scores on alertness, calmness and contentedness will be 'changed-from-baseline' and this score compared across the treatments. | 120 minutes and 240 minutes post dose on day 1 of treatment supplementation | 
| Interim changes in global cognitive task performance | Changes in attention, executive function, working memory and episodic memory as compared to pre-treatment performance on day 1. All tasks have the same x3 outcome measures; accuracy (% correct), errors (% incorrect) and speed (milliseconds) and the individual task scores will therefore be collapsed into global cognitive domains. | Day 7, day 14, day 21 and day 28 | 
| Chronic changes in cognitive task performance | Changes in executive function, working memory, spatial memory, secondary memory and attention as compared to pre-treatment performance on day 1. All tasks have the same x3 outcome measures; accuracy (% correct), errors (% incorrect) and speed (milliseconds) and the individual task scores will therefore be collapsed into global cognitive domains. | Pre-dose, 120 minutes and 240 minutes post-dose on day 29 of treatment supplementation | 
| Chronic changes in mood; as assessed by the Bond-Lader mood scales | The Bond-Lader mood visual analogue scales will be used at baseline and 120- and 240-minutes post dose on day 29. The derived scores on alertness, calmness and contentedness will be 'changed-from-baseline' and this score compared across the treatments. | Pre-dose, 120 minutes and 240 minutes post dose on day 29 of treatment supplementation | 
| Change in prospective memory performance; as assessed by a prospective memory task (the prospective remembering video task) | This individual task is called the Prospective Remembering Video Task (PRVP) and requires participants to remember a list of remembered locations and actions and identify these as they watch a video with them unfolding. The task is scored for difference in prospective memory/location learning performance between active and placebo on day 25 of supplementation period and also the difference in amount of memory decay of prospective memory/location learning on day 29 of treatment supplementation. | Day 25 and day 29 | 
| Acute changes in mood; as assessed by the 'state, trait anxiety inventory' (STAI) | The STAI will be used at baseline and 120- and 240-minutes post dose on day 1. The anxiety scores will be 'changed-from-baseline' and this score compared across the treatments. | 120 minutes and 240 minutes post dose on day 29 of treatment supplementation | 
| Chronic changes in mood; as assessed by the 'state, trait anxiety inventory' (STAI) | The STAI will be used at baseline and 120- and 240-minutes post dose on day 29. The anxiety scores will be 'changed-from-baseline' and this score compared across the treatments. | 120 minutes and 240 minutes post dose on day 29 of treatment supplementation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute changes in blood pressure | Changes in blood pressure (BP) as compared to pre-dose BP on day 1. BP is assessed via forearm cuff and provides systolic and diastolic BP. | 120 minutes and 240 minutes post dose on day 1 of treatment supplementation | 
| Chronic changes in blood pressure | Changes in blood pressure (BP) as compared to pre-dose BP on day 1. BP is assessed via forearm cuff and provides systolic and diastolic BP. | Pre-dose, 120 minutes and 240 minutes post dose on day 29 of treatment supplementation | 
| Acute changes in heart rate | Changes in heart rate (HR) as compared to pre-dose HR on day 1. HR is assessed via forearm cuff. | 120 minutes and 240 minutes post dose on day 1 of treatment supplementation | 
| Chronic changes in heart rate | Changes in heart rate (HR) as compared to pre-dose HR on day 1. HR is assessed via forearm cuff. | Pre-dose, 120 minutes and 240 minutes post dose on day 29 of treatment supplementation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sage, Terpene, Polyphenol, Cognition, Mood