The Acute and Chronic Cognitive Effects of a Sage Extract: a Randomized, Placebo Controlled Study in Healthy Humans
Phase: NA
Conditions: Cognitive Change, Mood Change
Sponsor: Northumbria University

Date: 22/06/18 
Study code: 55C2 
Study title: The acute and chronic cognitive effects of a sage extract: a randomized, 
placebo controlled study in healthy humans 
Ethics code: 8970 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

STUDY DESIGN AND PLAN 
The study will follow a randomised, double-blind, placebo-controlled, parallel groups design.  
 
STUDY PROCEDURES  
Testing will take place in a suite of testing facilities with participants visually isolated from 
each other. Participants will attend the laboratory on 3 separate occasions, an introductory 
visit between 1 and 14 days before the first day of treatment, and two testing days (Day 1 
and Day 29): 
The Introductory visit to the laboratory will comprise: briefing on requirements of the study, 
obtaining of informed consent, health screening, completion of the Caffeine Consumption 
Questionnaire (CCQ) and State-Trait Anxiety Inventory (STAI) trait subscale, training on the 
cognitive and mood measures and collection of demographic data. 
For the two ensuing laboratory-based testing sessions (Day 1, Day 29) participants will 
attend the laboratory before 8.00 am having consumed a standardised breakfast of cereal 
and/ or toast at home no later than an hour before arrival. They must have refrained from 
alcohol for 24 hours and caffeine for 18 hours. On arrival on each day participants will 
complete the State-Trait Anxiety Inventory (STAI) state subscale and the computerised 
cognitive assessment (as per Figure 1) followed by measurements of blood-pressure and 
heart rate. Immediately following this they will consume their treatment for that day. Two 
further cognitive assessments (plus BP and HR), identical to the pre-dose assessment will 
commence at 120- (~11:00 am) and 240 (~02:00 pm) minutes post-dose; the latter in order 
to take advantage of natural declines in performance during the day. Participants will be 
given a standardised lunch at approximately 12:10 pm. This lunch will comprise a white 
bread cheese sandwich, packet of ready salted crisps and custard pot. 
Cognimapp mobile phone assessments will take also place outside of the laboratory before 
the treatment period begins (Day -6 to -1) and at intervals of 7 (+/- 1 day) days (e.g. Day 7, 
14, 21, 28) with the final assessment taking place the day before the final laboratory visit. 
Assessments will take place in the morning (pre-dose) and evening on each day. 
Participants will be prompted by text messaging. Additionally, on Day 24, participants will 
complete the learning phase of the location-learning task. On day 28 the Cognimapp 
assessment will include completion of the retrieval phase of the location-learning task. 
Figures 2 and 3 depict the laboratory-based testing session timeline and chronic study 
overview respectively. 

 
Figure 1. The running order of the individual cognitive assessments. Tasks are shown in order of 
completion with approximate timings. On the left the ‘cognitive domain’ assessed by the task is shown 
and the boxes to the right show potential global measures into which data from several tasks can be 
collapsed.  
 
 
 
 
 
 
 
 
Word, Picture, 
Face/Name 
presentation
Immediate Word Recall
Stimuli
Presentation
Working Memory 
Attention
Episodic Memory
Minutes
Executive
Function
Choice Reaction Time
Numeric Working Memory
Bond Lader Mood Scales
Delayed Name/Face Recall
Delayed Word Recall
Delayed Pic’ Recognition
Delayed Word Recognition
Spatial
Working Memory
Episodic Memory
0
5
10
15
45
50
Corsi Blocks
Peg and Ball Task
Mood
Speed of Attention
Combined speed 
(msecs)
Working Memory 
Combined  accuracy 
(% correct)
Speed of Memory
Combined speed 
(msecs)
Episodic Memory
Combined accuracy 
(% correct)
Accuracy of Attention
Combined accuracy 
(% correct)
Cognitive Demand 
Battery
30 Minutes
3 repetitions of 
Serial 3s, Serial 
7s, RVIP, VAS
Cognitive Demand
(working memory
executive function
attention)
65

 
Figure 2. Testing session timeline on both the acute and chronic visit. participants complete a 
full cognitive assessment pre-dose and at 120 and 240 mins post-dose. Lunch is provided at 
approximately 12:10 pm. 
 
 
 
 
Figure 3. Overall trial diagram. Diagram includes screening/ training and main acute (day 1) and 
chronic (day 29) lab visit sessions. Weekly (day -6 to -1, 7, 14, 21 and 28) completion of the mobile 
phone battery and location-learning task completion (presented during day 25 and retrieved during 
day 29; with the intervening 3 days representing the memory decay phase) is also depicted. 
 
 
Treatment schedule across the study  
Participants will be provided with at least 30 days supply of the study’s investigational 
products (sage or placebo) for consumption daily between testing visits Day1 and Day 29 
and will undergo the cognitive/mood assessment on the first day (Day 1) and the last day 
(Day 29) of the active treatment period. The allocation to treatments will be undertaken via a 
randomly generated treatment schedule.   
Details of the mood assessments, COMPASS battery, CDB battery and mobile phone battery 
are presented in Appendices I, II, III and IV. 
 
 
 
0
120
Treatment
(08:00 am)
-60
Lunch
+ 240
(01:00 pm)
(09.00 am)
Cognitive assessment
Cognitive assessment
Cognitive assessment
(11.00 am)
(12.00 pm)
(12.10 pm)
(02:00 pm)
180
190
0
120
Treatment
(08:00 am)
-60
Lunch
+ 240
(01:00 pm)
(09.00 am)
Cognitive assessment
Cognitive assessment
Cognitive assessment
(11.00 am)
(12.00 pm)
(12.10 pm)
(02:00 pm)
180
190
-2-14 days
Screening/training
-1 days
Mobile phone battery completion
am
pm
am
am
am
am
pm
pm
pm
pm
Day 1
Day 7
Mobile phone battery completion
Day 14
Day 21
Mobile phone battery completion
Mobile phone battery completion
Day 25
Location-Learning (presentation/encoding phase)
Day 28
Mobile phone battery completion
Day 29
0
120
Treatment
(08:00 am)
-60
Lunch
+ 240
(01:00 pm)
(09.00 am)
Cognitive assessment
Cognitive assessment
Cognitive assessment
(11.00 am)
(12.00 pm)
(12.10 pm)
(02:00 pm)
180
190
Location-Learning (memory decay phase)
inc. Location-Learning (retrieval phase)

PLANNED ANALYSES 
Cognitive task data, mood scale and Blood Pressure (BP) analysis 
The cognitive task, mood and BP measures produce data that can be analysed to assess 
both acute (potential treatment effects within day 1 and day 29), pure-chronic (chronic 
treatment-related effects which have taken place across the 29 day supplementation period 
but prior to taking the day 29 treatment) and superimposed acute/chronic (the difference in 
‘acute’ effects between day 1 and day 29 or the difference in effects pre and post-dose on 
day 29) effects of treatment. In order to adequately analyse the ‘acute’, ‘pure chronic’ and 
‘superimposed acute/chronic’ effects of the treatments the following proposed analyses will 
be conducted: 
1.Pure acute effects 
To ascertain if any acute treatment effects have taken place, post-dose data from day 1 and 
day 29 will be baseline adjusted with regards the pre-dose baseline data collected on day 1 
and entered into a two way (treatment x assessment [120/240 min]) ANOVA. 
2. Pure chronic effects 
To ascertain if any pure chronic treatment effects have taken place, pre-dose data on day 29 
will be baseline adjusted with respect to day 1 pre-dose baseline data and analysed via 
ANOVA to compare performance between treatments. 
3. Acute, and superimposed effects 
i) To ascertain if any acute effects on day 1 have increased or attenuated over the 29 day 
treatment period, data from day 1 and day 29 will be baseline adjusted with respect to the 
respective day’s baseline assessment and entered into a three way (day x assessment x 
treatment) ANOVA. 
ii) To ascertain if there are differential chronic effects pre and post-dose on day 29, pre and 
post dose data from day 29 will be baseline adjusted with respect to the pre-dose baseline 
on day 1 and subjected to a two way ANOVA (treatment x assessment. 
 
The proposed a priori and post-hoc comparisons between treatment means to be utilised will 
be specified in the Statistical Analysis Plan 
 
 
Mobile phone battery analysis 
Data will be baseline adjusted and analysed by ANOVA (treatment (placebo and active) by 
day (7, 14, 21 and 28) by time (am and pm). 
 
 
State Trait Anxiety Inventory (STAI) 
Trate anxiety scores, collected during the screening/training visit will be compared between 
the treatment condictions to ensure that no differences exist between groups on this stable 
anxiety factor. 

State anxiety scores, collected prior to pre-dose cognitive tasks on day 1 and on day 29, will 
be converted into a change score (day 29 score minus day 1) and compared between 
treatments via ANOVA.