The Effect of Seven Day Prucalopride Administration on Emotional Processing in Healthy Volunteers
Phase: NA
Conditions: Molecular Mechanisms of Pharmacological Action, Depression, Depressive Disorder, Mood Disorders, Mental Disorders, Antidepressive Agents, Cognition
Sponsor: University of Oxford

CENTRAL UNIVERSITY RESEARCH ETHICS COMMITTEE (CUREC) 
CUREC 3 Protocol and Application Form 
Pharmacological Studies in Healthy Volunteers 
 
 
ONLY FULLY SIGNED TYPE-WRITTEN APPLICATIONS WILL BE ACCEPTED, BY EMAIL 
 
Please complete this Protocol and application form if your study involves the administration of a licensed 
drug, herbal remedy, or food supplement to healthy volunteers AND is not a clinical trial. 
 
All advisory text is highlighted in yellow and should be deleted before finalising the document. 
Should you require any assistance in completing this document, please contact CTRG in the first instance: 
http://researchsupport.admin.ox.ac.uk/ctrg 
 
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data 
STUDY DETAILS 
Full Study Title 
The effect of seven day prucalopride administration on emotional processing in 
healthy volunteers 
Internal Reference / Short 
title 
7 day prucalopride and emotional processing 
MS IDREC Reference 
R57219/RE001 
Date and version number 
Version Three, 16th May 2019 
Principal Investigator 
Dr Susannah Murphy 
Student (if applicable) 
N/A 
University email contact 
Susannah.murphy@psych.ox.ac.uk 
University telephone 
contact 
01865 618313 
Medically qualified 
collaborator (Licensed 
Doctor) 
Professor Phillip Cowen, MD, FRCPsych, FMedSci  
phil.cowen@psych.ox.ac.uk  
01865 618311 
Department of Psychiatry, University of Oxford 
Sponsor 
The University of Oxford 
External Funding 
None 
Will you submit or have you submitted this study to another ethics committee? 
Yes   
 
No  X 
If other relevant approvals for this research are required (e.g. from other universities’ ethics committees) please 
attach them and give more details below:  

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Declaration of any 
Conflicts of Interest 
None 
Confidentiality Statement 
This document contains confidential information that must not be disclosed to 
anyone other than the authorised individuals from the University of Oxford, the 
Investigator Team and members of the Medical Sciences Interdisciplinary 
Research Ethics Committee (Medical Sciences IDREC), unless authorised to do so. 
 
 
RESEARCH TEAM 
Investigator Title and 
name 
Professor Catherine Harmer  
Department / Institute 
name 
Department of Psychiatry, University of Oxford  
Role in Study 
Professor Harmer will be involved in the study design and interpretation of data.  
She is Professor of Cognitive Neuroscience, PhD Psychology, and has 20 years 
experience of experimental medicine studies. 
Training/Qualification in 
Research Ethics 
27th October 2016: Research Integrity Training (Epigeum) covering: protocols and 
associated documents; applications, agreements and approvals; trial master files; 
conducting the trial 
Investigator Title and 
name 
Professor Philip Cowen 
Department / Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study 
Professor Cowen will provide academic and medical supervision of the project. 
He is Professor of Pharmacology, MD, FRCPsych, FMedSci 
Training/Qualification in 
Research Ethics 
'Training in Good Clinical Practice and Clinical Trial Methodology and 
Administration' (refresher course June 2011). Protocol and Associated 
Documents Course March 2013.  Adverse Event Reporting (online CTRG training) 
2017 
Investigator Title and 
name 
Dr. Jessica Scaife 
Department / Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study  
Recruitment, data collection, analysis  
Training/Qualification in 
Research Ethics 
Good Clinical Practise (Epigeum) training, completed 06/03/2018 
Magnet Safety Training, completed 10/01/2018 

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Investigator Title and 
name 
Miss Lucy Wright 
Department / Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study  
Recruitment, data collection, analysis 
Training/Qualification in 
Research Ethics 
Good Clinical Practise for Clinical Research Studies training, completed 
15/11/2016  
Magnet Safety Training, completed 10/01/2018 
Investigator Title and 
name 
Miss Elizabeth Haris 
Department / Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study 
Recruitment, data collection, analysis 
Training/Qualification in 
Research Ethics 
Good Clinical Practise for Clinical Research Studies training, completed 
20/11/2017  
Magnet Safety Training, completed on 14/02/2018 
Investigator Title and 
name 
Ms Amy Gillespie  
Department / Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study 
Recruitment, data collection, analysis 
Training/Qualification in 
Research Ethics 
Good Clinical Practise for Non-CTIMPs, Guys Hospital, completed 17/08/2016   
Magnet Safety Training, completed 10/01/2018 
Investigator Title and 
name 
Dr Angharad de Cates 
Department / Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study 
Recruitment, data collection, analysis 
Training/Qualification in 
Research Ethics 
Good Clinical Practice (eGCP (Secondary Care)), completed 03/05/2017 
Magnet Safety Training, completed 13/02/2019 
 

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1. TABLE OF CONTENTS 
 
1. TABLE OF CONTENTS ........................................................................................................................................................... 4 
2. SYNOPSIS ............................................................................................................................................................................. 5 
3. ABBREVIATIONS ................................................................................................................................................................... 8 
4. BACKGROUND AND RATIONALE .......................................................................................................................................... 9 
5. PARTICIPANTS .................................................................................................................................................................... 10 
6. STUDY PROCEDURES ......................................................................................................................................................... 13 
7. INTERVENTION(S) .............................................................................................................................................................. 16 
a) 
Drug/Substance 1 ..................................................................................................................................................... 16 
b) 
Drug/Substance 2 (or placebo) ................................................................................................................................. 17 
8. SAFETY ............................................................................................................................................................................... 17 
a) 
Definitions ................................................................................................................................................................ 17 
b) 
Reporting Procedures for Serious Adverse Events or Reactions .............................................................................. 18 
c) 
Safety of Participants ................................................................................................................................................ 19 
d) 
Ethical Considerations .............................................................................................................................................. 21 
9. STATISTICS AND ANALYSIS ................................................................................................................................................. 22 
10. DATA MANAGEMENT ........................................................................................................................................................ 23 
11. STUDY MONITORING AND OVERSIGHT ............................................................................................................................. 26 
12. ETHICAL AND REGULATORY CONSIDERATIONS ................................................................................................................. 26 
Declaration of Helsinki ...................................................................................................................................................... 26 
Approvals .......................................................................................................................................................................... 26 
Annual Progress Report .................................................................................................................................................... 26 
13. INSURANCE STATEMENT ................................................................................................................................................... 26 
14. DISSEMINATION AND FEEDBACK OF STUDY OUTCOMES .................................................................................................. 27 
15. REFERENCES ...................................................................................................................................................................... 27 
16. DECLARATIONS AND SIGNATURES OF RESEARCHERS ....................................................................................................... 28 
17. ACCEPTANCE BY HEAD OF DEPARTMENT/FACULTY* ........................................................................................................ 28 
18. AMENDMENT HISTORY...................................................................................................................................................... 29 
19. APPENDIX A: Study Adverts ............................................................................................................................................... 30 
20. APPENDIX B: Re-contact Email Template .......................................................................................................................... 32 
21. APPENDIX C: Screening Form ............................................................................................................................................ 33 
22. APPENDIX D: MRI Screening Form .................................................................................................................................... 38 
23. APPENDIX E: Participant Information Sheet (PIS) .............................................................................................................. 39 
24. APPENDIX F: Informed Consent Form (ICF) ....................................................................................................................... 47 
25. APPENDIX G: Study Questionnaires    ................................................................................................................................ 50 
26. APPENDIX H: Encapsulation Standard Operating Procedure (SOP)  ..................................... Error! Bookmark not defined. 

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27. APPENDIX I: WIN/OCMR/OHBA Standard Operating Procedure (SOP) – 'Dealing With Research Neuroimaging 
Incidental Findings' ............................................................................................................................................................... 79 
 
2. SYNOPSIS 
Please state 
why this study 
is not 
considered a 
Clinical Trial of 
an 
Investigative 
Medicinal 
Product 
This study is not a clinical trial as we are not investigating the efficacy of prucalopride, but 
rather using it as a probe to understand the role of 5-HT4 receptors in emotional 
processing.  
This study does not fit the MHRA definition of a clinical trial as one designed to: discover 
or verify/compare a drug’s clinical effects; to discover or verify/compare its 
pharmacological effects (e.g. pharmacodynamics); to identify or verify/compare its 
adverse reactions; or to study its absorption, distribution, metabolism or excretion 
(https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/31795
2/Algothrim.pdf)  
List all sites 
where study 
will be 
conducted 
Department of Psychiatry, Warneford Hospital, University of Oxford  
Oxford Centre for Human Brain Activity (OHBA), Warneford Hospital, University of Oxford  
Age Range of 
Study 
Participants 
18-40 years 
Planned 
Sample Size 
50 healthy volunteers (25 per group) 
Planned Study 
Duration 
(n.b. A minimum 
approval period 
of 1 year and 
maximum of 5 
years can be 
granted) 
24 months  
Anticipated 
Start Date 
1st March 2018 
Anticipated 
End Date 
1st March 2020 
 
Objectives 
Outcome Measures 
Primary 
 
To investigate the effects of seven day prucalopride 
administration on  
1. Recognition of positive and negative facial 
expressions 
2. Performance on Auditory Verbal Learning Task 
1. Accuracy (%) and 
reaction times on 
computer-based 
task of facial 
expression 
recognition (FERT), 
comparing those 

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(AVLT) 
 
receiving drug and 
placebo. 
2. Number of words 
correctly recalled 
across blocks (and 
number of 
intrusions and 
repetitions) 
 
 
Secondary 
To investigate the effects of seven day prucalopride 
administration:  
1. Amygdala response to emotional faces  
2. Hippocampal response to novel versus repeated 
scenes 
3. Reward sensitivity  
4. Categorisation, recall and recognition of emotional 
words 
 
1. BOLD fMRI signal 
in the amygdala 
during emotional 
faces task 
presentation 
2. BOLD fMRI signal 
in hippocampus to 
pictures of familiar 
versus novel 
scenes.  
3. Amount won, 
amount lost, total 
monetary amount 
earned during the 
task, proportion of 
participants 
choosing the 
correct symbol in 
win and loss trials 
of the PILT, 
comparing those 
receiving drug and 
placebo 
4. Number of positive 
and negative 
words correctly 
categorised, 
recalled, and 
recognised on 
emotional memory 
task 
 

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Tertiary 
To investigate the effects of seven day prucalopride 
administration on:  
1. Vigilance to fearful and happy faces 
2. Resting state networks 
3. Visual short term memory  
4. Cerebral blood flow using arterial spin labelling 
(ASL)  
 
 
1. Reaction times to 
fearful, happy, and 
neutral faces in 
masked and 
unmasked 
conditions  
2.  BOLD fMRI activity 
during resting state  
3.  Accuracy and 
reaction time on 
the Oxford 
Memory Task 
(OMT) 
4. Relative and global 
cerebral blood flow 
using arterial spin 
labelling (ASL)  
 
 
Name of 
drug/substance 
Prucalopride (Resolor) 
Purpose of 
drug/substance 
use in this 
study 
Work in our group has revealed that short-term (7 day) administration of antidepressants 
that boost serotonin levels produces positive biases in the processing of emotional 
information in healthy volunteers. Such effects might be an important neuropsychological 
mechanism of antidepressant action. It is unclear whether particular serotonin receptor 
subtypes are particularly important in mediating these effects. The current study 
investigates the effect of seven-day administration of a specific agonist of the 5-HT4 
receptor subtype (Prucalopride) on emotional processing tasks. There is evidence that 5-
HT4 agonists may exert antidepressant and anxiolytic effects in animal models, and it is 
therefore predicted that prucalopride will have similar effects to serotonergic 
antidepressants on emotional processing. A previous study in our group demonstrated 
that a single dose of prucalopride potentiated learning and memory in healthy volunteers, 
but had no effect on emotional processing.  This study aims to investigate whether a 
longer (7 day) administration of prucalopride has effects on the neural and behavioural 
response to emotional stimuli that are consistent with an antidepressant profile.   
Adverse 
reactions and 
side effects 
posing a 
particular risk 
The side effects associated with prucalopride are headache, gastrointestinal symptoms 
(abdominal pain, nausea, diarrhoea), decreased appetite, vomiting, flatulence, and 
fatigue.  
There is limited information about the effects of a single dose of prucalopride in healthy 
volunteers, with most reported information about side effects coming from patients with 

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with this 
treatment 
constipation.   Pilot work in our group demonstrated that the standard 2mg dose of 
prucalopride was not well tolerated in healthy volunteers, with two out of three pilot 
participants experiencing diarrhoea following a single 2mg dose.   
As a result of this pilot work, we used a 1mg dose of prucalopride in our previous study, 
which was well tolerated by healthy volunteers.  The main side effects reported by 
participants in this study were fatigue, gastrointestinal sounds, and headache, but the 
rate of report of these side effects was not higher in the prucalopride group compared 
with the placebo group. We therefore plan to use the same 1mg dose in the current 
study.   
 
3. ABBREVIATIONS 
5-HT 
Serotonin 
ANOVA 
Analysis of Variance 
BDI 
Beck Depression Inventory 
BMI 
Body Mass Index  
BOLD 
Blood Oxygen Level Dependent  
BPG 
Best Practice Guidance 
CTRG 
Clinical Trials & Research Governance, University of Oxford 
CUREC 
Central University Research Ethics Committee 
DSM 
Diagnostic and Statistical Manual of Mental Disorders  
EPQ 
Eysenck Personality Questionnaire  
ETB 
Emotional Test Battery 
fMRI 
Functional Magnetic Resonance Imaging  
FSL 
FMRIB Software Library 
GCP 
Good Clinical Practice 
GP 
General Practitioner 
ICF 
Informed Consent Form 
JCR 
Junior Common Room  
MCR 
Middle Common Room  
MS IDREC 
Medical Sciences Inter-Divisional Research Ethics Committee 
NART 
National Adult Reading Test  
OHBA 
Oxford Centre for Human Brain Activity  
PANAS 
Positive and Negative Affective Schedule  
PI 
Principal Investigator 
PIL 
Probabilistic Instrumental Learning 
PIS 
Participant Information Sheet 
SAE 
Serious Adverse Event 

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SCID-V 
Structured Clinical Interview for DSM-V 
SHAPS 
Snaith-Hamilton Pleasure Scale  
SOP 
Standard Operating Procedure 
SPSS 
Statistical Package for the Social Sciences 
SSRI 
Selective Serotonin Reuptake Inhibitor 
STAI 
Spielberger State-Trait Anxiety Inventory 
VAS 
Visual Analogue Scales  
 
4. BACKGROUND AND RATIONALE 
Depression is a common condition which is associated with substantial health disability (1). Selective 
Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed antidepressants. However, for many 
patients these drugs have limited efficacy, a poor side-effect profile, and a slow onset of therapeutic action 
(2). Pharmacologically, SSRIs produce an indirect activation of several serotonergic receptor subtypes. It is 
possible that more specifically targeting particular receptor subtypes may be a potentially useful approach to 
the development of antidepressant treatment that is more effective, better tolerated and faster acting.  
Recent evidence from animal studies suggests that agonists of the serotonin receptor subtype 4 (5-HT4 ) have 
rapid effects on depression- and anxiety-related behaviours. For example, administration of the 5- HT4 
agonists RS67333 and prucalopride reduces immobility in the forced swim test (3). Consistent with this, in a 
mouse corticosterone model of anxiety/depression, RS67333 produced rapid anxiolytic and antidepressant 
effects in a battery of tests, including the open field test, the elevated plus maze, the tail suspension test and 
the novelty suppressed feeding test (4). Importantly, these effects were seen after only three days of 
treatment (3,4), whereas they are usually only observed after chronic (2-3 week) treatment with conventional 
SSRIs. This raises the intriguing possibility that 5-HT4 agonism might lead to more rapid and sustained 
activation of 5-HT neurons than SSRIs, and therefore potentially more rapid reductions in symptoms of 
depression when used clinically.  
Work in our group has revealed that short-term treatment with conventional antidepressants such as SSRIs 
produces positive biases in the processing of emotional information in healthy volunteers (5). For example, 
seven days treatment with the SSRI citalopram decreased recognition of negative facial expressions and recall 
of negative vs positive stimuli (6). There is also evidence showing that antidepressants have early effects on 
neural activity, acting on limbic-cortical brain regions that are known to be dysregulated in depression (7). 
Indeed, a key study by Godlewska and colleagues from our group showed that 7-day treatment with 
citalopram reduced activity in the anterior cingulate, insula, amygdala and thalamus in response to fearful 
versus happy facial expressions. Importantly, depressed patients with the greatest reduction in neural activity 
across these areas went on to respond better to SSRI treatment (8). 
Such effects might be important neuropsychological mechanisms in the mediation of clinical antidepressant 
action and may also be useful as biomarkers to screen for potential antidepressant activity of novel 
compounds. It is currently unknown whether activating 5-HT4 receptors has similar effects on emotional 

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processing and neural activity. Such findings would be consistent with the animal studies and important 
further demonstration that 5-HT4 receptor agonism might be a potentially useful avenue for antidepressant 
drug development. A previous study in our group revealed acute prucalopride administration (1mg) in 40 
healthy volunteers potentiated learning and memory, whereby significantly more words were remembered in 
a test of auditory verbal learning and memory, and fewer false alarms were made in a delayed emotional 
recall task relative to placebo. A single dose of prucalopride did not, however, positively bias emotional 
processing.  
This current study will therefore test the hypothesis that short-term, seven-day administration of 
prucalopride will have positive effects on emotional processing and neural activity. Prucalopride (“Resolor”) is 
a 5-HT4 receptor agonist which is currently licensed for the symptomatic treatment of chronic constipation in 
adults. The standard dose given is 2 mg once daily with or without food, at any time of the day. Healthy 
volunteers will be randomised to receive seven days of prucalopride (1 mg i.e. half the standard dose) or 
placebo. On the seventh day of drug administration, they will complete a battery of computer-based tasks 
that measure emotional processing (tasks of attention, interpretation, and memory), non-emotional 
cognition, and undergo fMRI scanning during an emotional processing task.  
 
5. PARTICIPANTS 
Description of Study Participants 
50 Healthy Volunteers aged between 18 and 40 years 
Inclusion Criteria 
 
Participant is willing and able to give informed consent for participation in the study 
 
Not currently taking any medications (except the contraceptive pill) 
 
Male or female 
 
Aged 18-40 years 
 
Sufficiently fluent English to understand and complete the task  
 
Right handed 
 
Body Mass Index in the range of 18-30 
Exclusion criteria 
The participant may not enter the study if ANY of the following apply: 
 
Not fluent in English  
 
Any past or current Axis 1 DSM-V psychiatric disorder  
 
Current usage of psychoactive medication (except the contraceptive pill, the Depo-
Provera injection or the progesterone implant)  
 
Current usage of any medication that will influence the MRI scan (the researcher will 

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help you decide this)  
 
Current or past history of drug or alcohol dependency  
 
Currently pregnant or breastfeeding  
 
Study visits due to take place during the pre-menstrual week (female participants 
will be asked details of their menstrual cycle to schedule the study outside this week)  
 
Not right handed  
 
Body Mass Index outside the range of 18-30  
 
History of cardiac, thyroid, or liver problems  
 
An autoimmune disorder  
 
Current, or a history of, gastro-intestinal disorder or irritable bowel syndrome  
 
Epilepsy  
 
Known lactate deficiency or any other problem absorbing lactose, galactose, or 
glucose  
 
Participation in a study which uses the same computer tasks as those used in the 
present study  
 
Participation in a study that involves the use of a medication within the last three 
months  
 
Smoker > 5 cigarettes per day  
 
Typically drinks > 6 caffeinated drinks per day  
 
Any contraindication to MRI scanning (e.g. metal objects in your body, pacemakers, 
significant claustrophobia)  
 
Recruitment 
Participants will be recruited via adverts (see APPENDIX A: STUDY ADVERTS) sent to Junior Common Rooms 
(JCRs) and Middle Common Rooms (MCRs), displayed in colleges and university departments and local 
community buildings through existing participant registries at the Department of Psychiatry and the 
Department of Experimental Psychology. Participants will also be recruited via advertisement through Oxford 
Brookes, following approval from Oxford Brookes University Research Ethics Committee. The following 
additional statement will be inserted into any recruitment documents for Oxford Brookes students and/or staff: 
"Oxford Brookes University has knowledge of this study and has permitted recruitment at the University. In the 
event of any questions about the study, please contact the researchers in the first instance. Should you need to 
contact anyone at Oxford Brookes about this further, please email: ethics@brookes.ac.uk".  Adverts may also 
be placed on local information websites (e.g. Daily Info, Oxford University Gazette), newspapers, local 
magazines, on the radio and on the lab webpage, Facebook page and Twitter account.  The adverts will contain 
brief information about the inclusion criteria for the study, as well as contact details for the named researchers.   
After a potential volunteer has contacted the research team, they will be sent the Participant Information 
Sheet via email. We will also send the Participant Information Sheet via email (APPENDIX B: RECONTACT EMAIL 
TEMPLATE) to participants from a previous study who gave consent to be approached about possible 
participation in future research studies they may be suitable for. The participant will be given as much time as 
they need to decide whether they would like to take part, and will be invited to ask any questions that they 
have about the study.  If the participant decides that they do not want to take part in the study, they will be 
thanked for their interest and there will be no further contact from the research team.  If the participant 
decides they would like to take part, they will be invited for a screening visit at the Department of Psychiatry, 
Warneford Hospital. At the beginning of this visit, one of the named researchers will explain the study to the 
participant and answer any questions that he/she has.  The researcher will then take written consent from the 

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participant.  All of the named researchers have been trained in taking informed consent.     
Screening and Eligibility Assessment 
Informed Consent is obtained at the start of the screening, prior to administration of questionnaires or the 
Structured Clinical Interview for DSM-V Disorders.   
A maximum of four weeks is allowed between screening and randomisation to prucalopride or placebo. If this 
duration is exceeded, another screening will need to be performed to ensure eligibility. 
At screening, information about demographics, medical history, concomitant medication and psychiatric 
history will be taken (using Structured Clinical Interview for DSM-V). See APPENDIX C: SCREENING FORM.  
An MRI screening form will be completed to ensure it is safe for participants to undergo fMRI scanning (see 
APPENDIX D: MRI SCREENING FORM).  
Female participants will take a urine pregnancy test.  
Information Provided to Participants and Informed Consent 
The Participant Information Sheet (see APPENDIX E: PARTICIPANT INFORMATION SHEET) will be presented to 
the participants, as well as in verbal form. Both will detail the exact practical demands of the study, written 
from the participant's perspective, in lay language (the nature of the study, what it will involve for the 
participants, the implications and constraints of the protocol, the known side effects and any risks involved in 
taking part, what will happen to the data collected). It will be clearly stated that the participant is free to 
withdraw from the study at any time for any reason and with no obligation to give the reason for withdrawal.  
The participant will be allowed as much time as they wish to consider the information, and the opportunity to 
question the Investigator, their General Practitioner (GP) or other independent parties to decide whether they 
will participate in the study.   
The participant must personally sign and date the latest approved version of the Informed Consent Form (ICF; 
see APPENDIX F: INFORMED CONSENT FORM) before any study specific procedures are performed.  
Written Informed Consent will then be obtained by means of participant dated signature and dated signature 
of the person who presented and obtained the Informed Consent. The person who obtained the consent will be 
suitably qualified and experienced, and have been authorised to do so by the Principal Investigator (PI). A copy 
of the signed ICF will be given to the participant. The original signed form will be retained at the study site.  
Participant Confidentiality 
It will made clear to the participant that information shared within the course of the screening and study visits 
may be shared within the research team, but will not be shared with anyone else.  The exceptions to this are 
stated clearly in the Participant Information Sheet:   
“Information collected about you during the course of the research would be kept confidential. Confidentiality 
would be breached only in the very rare circumstance that it was judged that you or someone else was at 
immediate risk of serious harm. In these circumstances only information necessary to ensure immediate safety 
would be released. The only other circumstance in which information would be released is if it was requested 
by an order of a court of law.“ 
 
 

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6. STUDY PROCEDURES 
Baseline Assessments and Procedures 
Individuals who are interested in participating in the study will be invited to attend a Screening Visit (maximum 
2 hours). Demographic information will be collected:  
 
Age (years, months), years in full-time education  
Participants' eligibility to take part will be checked by recording the following:  
 
Weight, height, and BMI  
 
Number of cigarettes smoked per day, units of alcohol consumed per week, caffeinated drinks 
consumed per day  
 
Medical history (including family psychiatric history), details of current and past medication  
 
Current and prior use of drugs (to exclude for drug use in the 
three months prior to the study)    
 
Menstrual cycle (in order to avoid scheduling testing in the 
premenstrual week) 
 
SCID-V interview (Structured Clinical Interview for DSM-V) to probe for current or past psychiatric 
illness  
 
Urine pregnancy test (female participants only)  
 
MRI screening form to ensure no contraindication to MRI scanning  
 
Edinburgh Handedness Inventory  (see APPENDIX G: STUDY QUESTIONNAIRES) 
The following baseline assessments will be completed (APPENDIX G):  
 
Beck Depression Inventory (BDI)  
 
Eysenck Personality Questionnaire (EPQ) 
 
State and Trait Anxiety Inventory (STAI)  
 
Positive and Negative Affect Schedule (PANAS)  
 
Snaith-Hamilton Pleasure Scale (SHAPS) - a measure of anhedonia  
 
National Adult Reading Test (NART) - a measure of verbal intelligence  
 
Side effect questionnaire (to determine baseline of bodily symptoms/’side effects’)  
 
Visual Analogue Scales (VAS) measuring subjective state  
Participants will be asked to wait while their eligibility to take part is assessed by a medical doctor involved in 
the study (maximum 30 minutes). Any participant for whom additional information is required before an 
eligibility judgment can be made will be asked to return on a different day once this information has been 
obtained.  
Eligible participants will be randomised, using an online randomisation tool, to receive either seven-day 
prucalopride, or seven-day placebo administration. Randomisation will occur on the day of screening, or up to a 
maximum of four weeks after screening. Randomisation after the screening visit will occur in the event that 
further information is needed before determining whether participants are eligible to take part (for example, if 
a participant needs to follow up with details of allergies, or previous studies they have taken part in). In this 

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case, if more than four weeks has elapsed, another screening visit will be performed to ensure participants are 
still eligible.  
 
Randomised participants will be given seven days of the drug to take home, as well as full instructions of how 
and when to take them. The study has a double blind design thus neither the researchers nor the participant 
will know whether prucalopride or placebo is given.  
During the week of drug/placebo administration, participants will be advised not to drink alcohol and not to 
carry out activities requiring full alertness, such as driving, if they are aware of any impairment. During this 
week, a researcher will phone up the participant on day 2 and day 4 to check that there are no concerns. 
Additionally, participants will receive a text message every day reminding them to take the study medication.  
They will have the 24-hour contact phone number of a member of the study team and be encouraged to get in 
contact if they have any concerns or queries during the study week, or if their medication or health status 
changes. 
 
Subsequent Visits 
1. Research Visit One (approximately 1.5 hours) on day 6 of prucalopride/placebo administration. This visit will 
involve an fMRI scan taking place at the Oxford Centre for Human Brain Activity (OHBA), which is part of the 
Department of Psychiatry on the Warneford Hospital site.  
On arrival, participants will complete the MRI screening form (APPENDIX D) once more to ensure it is still safe 
for them to undergo fMRI scanning.  
Participants will complete the following questionnaires before and after the fMRI scan:  
 
State Anxiety Inventory (STAI-S)  
 
Positive and Negative Affect Schedule (PANAS)  
 
Side effect questionnaire  
 
Visual Analogue Scales (VAS)  
The scan itself will include:  
 
Structural scan  
 
Emotional faces task  
 
Memory task  
 
Resting state 
 
Arterial spin labelling  
 
Physiological recordings including pulse, respiration, and skin conductance – recorded using a pulse 
meter, respiration bellows and electrodes strapped by Velcro to fingertips.  
 
Eye tracking 
 
2. Research Visit Two (approximately 2 hours) on day 7 of prucalopride/placebo administration. This visit will 
involve administration of behavioural tasks measuring emotional and non-emotional cognitive processing.   
Participants will complete the following questionnaires before and after the behavioural tasks:  

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 
State Anxiety Inventory (STAI-S)  
 
Positive and Negative Affect Schedule (PANAS)  
 
Side effect questionnaire  
 
Visual Analogue Scales (VAS)  
The behavioural tasks will include the Emotional Test Battery (ETB), which has previously been found to be 
sensitive to the effects of antidepressants, two tests of learning and memory, and a reward task (Probabilistic 
Instrumental Learning; PIL).  The ETB involves the presentation of emotion-related words and pictures of faces 
with different expressions. The reward task involves repeatedly choosing between two options and there is the 
possibility of winning up to £10 depending on the choices made (see 'Expenses and Benefits' below). All stimuli 
will be presented on a computer screen and participants will be required to respond via button presses on a 
keyboard.  
Participants will be asked to report their adherence to the seven-day administration.  
At the end of the research visit, a member of the study team will ask participants to try to guess which 
treatment they received, as a measure of how successful the blinding was.  
 
Sample Handling 
Female participants will be required to give a urine sample for a pregnancy test at the screening visit. Urine 
samples will be destroyed immediately after the test result has been obtained.  
Discontinuation/Withdrawal of Participants from Study 
Each participant has the right to withdraw from the study at any time.  In addition, the Investigator may 
discontinue a participant from the study at any time if the Investigator considers it necessary for any reason 
including: 
 
Pregnancy 
 
Ineligibility (either arising during the study or retrospectively having been overlooked at screening) 
 
Significant protocol deviation 
 
Significant non-compliance with treatment regimen or study requirements 
 
Withdrawal of Consent 
 
Loss to follow up 
 
If a participant is withdrawn, no further procedures or observations will continue to be required. Withdrawal 
from the study will result in exclusion of the data for that participant from analysis. Withdrawn participants will 
be replaced. The reason for withdrawal if given will be recorded in the Participant Log of the Research Master 
File.  
Definition of End of Study 
The end of the study for participant involvement is the date of the last visit of the final participant.  
Expenses and Benefits 

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Participants will be paid £120 upon completion of their participation in the research. In addition, they may win 
up to £10 depending on the choices they make in the reward task (see 'Subsequent Visits' above). If they do not 
complete the study, they will be given a pro-rata amount to recompense the time they did spend in the study. 
Reasonable travel expenses for any visits will be reimbursed on production of receipts, or a mileage allowance 
provided as appropriate. 
 
 
7. INTERVENTION(S) 
a) Drug/Substance 1 
Name of drug/substance to be used 
Prucalopride 
Formulation and route of administration for 
study 
1mg prucalopride tablets will be encapsulated in opaque 
capsules.  
Dose and route of administration for study 
1mg oral dose, daily 
Duration of treatment for study 
Seven days  
Licence status of this drug/substance 
Prucalopride is a licensed drug.  
Usual Indication 
Prucalopride is indicated for the symptomatic treatment of 
chronic constipation in adults. 
Usual Dose 
The usual dose given is 2 mg once daily with or without food, 
at any time of the day. 
Usual duration of treatment 
Prucalopride can be administered long- term, although the 
efficacy of the drug in the treatment of constipation has only 
been established up to 3 months. 
Where will drug/substance be sourced from? 
The drug will be sourced from the Oxford Pharmacy Store, 
Kennington in the form of 1mg film-coated tablets.  
Where will drug/substance be stored? 
Prucalopride will be stored within the Neurosciences 
Building at the Department of Psychiatry. It will be stored at 
room temperature in a locked cupboard, which is suitable 
for drug storage. 
How will drug/substance be dispensed? 
Prucalopride will be dispensed from the Neurosciences 
Building by a study medic or nurse.  
How will the drug/substance be prepared by 
the researchers for use in this study? 
Prucalopride will be encapsulated by trained clinical trial 
support staff using our Standard Operating Procedure (see 
protocol APPENDIX H: ENCAPSULATION STANDARD 
OPERATING PROCEDURE (SOP)). 

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b) Drug/Substance 2 (or placebo) 
Name of drug/substance to be used 
Lactose Placebo  
Formulation and route of administration for 
study 
Placebo tablets will be encapsulated in opaque capsules. 
Dose and route of administration for study 
One capsule taken orally, daily 
Duration of treatment for study 
Seven days  
Licence status of this drug/substance 
N/A 
Usual Indication 
N/A 
Usual Dose 
N/A 
Usual duration of treatment 
N/A 
Where will drug/substance be sourced from? 
Placebo tablets will be sourced from HSC 
(www.hsconline.co.uk).  
Where will drug/substance be stored? 
Placebo tablets will be stored within the Neurosciences 
Building at the Department of Psychiatry. It will be stored at 
room temperature in a locked cupboard, which is suitable 
for drug storage.  
How will drug/substance be dispensed? 
Placebo tablets will be dispensed from the Neurosciences 
Building by a study medic or nurse. 
How will the drug/substance be prepared by 
the researchers for use in this study? 
Placebo tablets will be encapsulated by trained clinical trial 
support staff using our Standard Operating Procedure (see 
protocol APPENDIX H: ENCAPSULATION STANDARD 
OPERATING PROCEDURE (SOP)). 
 
 
8. SAFETY 
a) Definitions 
Adverse Event (AE) 
Any untoward medical occurrence in a participant to whom a substance has been 
administered, including occurrences which are not necessarily caused by or related 
to that substance. 
Adverse Reaction (AR) 
An untoward and unintended response in a participant to a substance, which is 

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related to any dose administered to that participant. 
A causal relationship between the administered substance and an AE is at least a 
reasonable possibility, i.e. the relationship cannot be ruled out. 
All cases judged by either the reporting medically qualified professional or the 
Sponsor as having a reasonable suspected causal relationship to the study 
intervention qualify as adverse reactions. 
Serious Adverse Event 
(SAE) 
A serious adverse event is any untoward medical occurrence that: 
 results in death 
 is life-threatening 
 requires inpatient hospitalisation or prolongation of existing hospitalisation 
 results in persistent or significant disability/incapacity 
 consists of a congenital anomaly or birth defect. 
Other ‘important medical events’ may also be considered serious if they jeopardise 
the participant or require an intervention to prevent one of the above 
consequences. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event 
in which the participant was at risk of death at the time of the event; it does not 
refer to an event which hypothetically might have caused death if it were more 
severe. 
Serious Adverse Reaction 
(SAR) 
An adverse event that is both serious and, in the opinion of the reporting 
Investigator, believed with reasonable probability to be due to one of the study 
treatments, based on the information provided. 
Suspected Unexpected 
Serious Adverse Reaction 
(SUSAR) 
A serious adverse reaction, the nature and severity of which is not consistent with 
the information about the medicinal product set out in its summary of product 
characteristics (SmPC). 
 
b) Reporting Procedures for Serious Adverse Events or Reactions 
A serious adverse event (SAE) occurring to a participant should be reported to CTRG and the Medical Sciences 
IDREC where, in the opinion of the Principal Investigator, the event was ‘related’ (resulted from 
administration of any of the research procedures) and ‘unexpected’ (the type of event is not listed in the 
protocol as an expected occurrence).  Reports of related and unexpected SAEs should be submitted within 15 
days of the Principal Investigator becoming aware of the event.  For fatal and life-threatening SUSARs, this will 
be done no later than 7 calendar days after the Sponsor or delegate is first aware of the reaction.  Any 
additional relevant information will be reported within 8 calendar days of the initial report. 

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c) Safety of Participants 
What level of baseline screening will take place for this study? 
All participants will undergo a Screening Visit to ensure only eligible participants take part. The following will be 
recorded at baseline screening:   
 
Demographic information (age [years, months], years in full-
time education)  
 
Number of cigarettes smoked per day, units of alcohol 
consumed per week, caffeinated drinks consumed per day  
 
Current and prior use of drugs (to exclude for drug use in the 
three months prior to the study)   
 
SCID-V interview (Structured Clinical Interview for DSM-V) to 
probe for current or past psychiatric illness 
 
Beck Depression Inventory (BDI)  
 
Eysenck Personality Questionnaire (EPQ) 
 
State and Trait Anxiety Inventory (STAI) 
 
Positive and Negative Affect Schedule (PANAS) 
 
Snaith-Hamilton Pleasure Scale (SHAPS)  
 
National Adult Reading Test (NART)  
 
Edinburgh Handedness Inventory 
 
Side effect questionnaire 
 
Visual Analogue scales (VAS)  
To ensure it is safe to administer the drug to the participant, the following will be recorded:  
 
Weight, height, and BMI  
 
Medical history (including family psychiatric history)  
 
Details of current and past medication  
 
Urine pregnancy test (female participants only)  
To ensure it is safe for the participant to undergo fMRI scanning, the following will be administered  
 
MRI safety form to ensure no contraindication to MRI 
scanning  
Participation in prior studies will be recorded to exclude for individuals who have used the same/similar 
emotional processing tasks.  
Provide details about the safety monitoring of participants and the staff/researchers carrying this out 
During the week of drug/placebo administration, participants will be advised not to drink alcohol and not to 
carry out activities requiring full alertness if they are aware of any impairment. During this week, a researcher 
will phone up the participant on day 2 and day 4 to check that there are no concerns. Participants will have the 
24-hour contact phone number of a member of the study team and be encouraged to get in contact if they 
have any concerns or queries during the study week, or if their health status changes. The named researcher 
will in turn contact a qualified medical doctor if necessary.  

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Give details on the medical cover required and who will provide this cover 
A medical doctor who is part of the research team will review the screening and make a final judgment about 
including participants in the study. A qualified medical doctor will be contacted if a participant expresses 
concern to a named researcher regarding side effects or health status changes during the study week.  
Will the participants’ GP be informed about their participation in the study?  In not, please justify 
Participants’ GPs will not be informed about their participation in the study. Seven days of low-dose 
prucalopride (1mg) administration is not regarded as a clinically significant intervention and is not expected to 
have any impact on participants’ health or wellbeing. We are excluding participants who are pregnant, 
breastfeeding or who have any medical conditions for whom the study would not be suitable.  
What is your planned procedure if an incidental finding is suspected? 
The detailed images obtained from MRI scanners, while not suitable for clinical diagnosis, may on rare 
occasions identify unexpected structural abnormalities. If an abnormality is noted on the structural scan of a 
healthy volunteer, the “WIN/OCMR/OHBA Standard Operating Procedure – Dealing with Research 
Neuroimaging Incidental Findings” will be strictly followed.   
Participants will be screened to exclude those with past or current psychiatric symptoms and Best Practice 
Guidance (BPG) 08 (Psychological distress) will be followed in order to ensure best practice in situations where 
participants with psychological distress are identified.  The guidance in this document around confidentiality 
and researcher training will also be adhered to.   
If an incidental finding has clinical implications, what action will you take? 
During the consent process, subjects would be informed of our standard procedure for incidental findings 
(“WIN/OCMR/OHBA SOP – Dealing with Research Neuroimaging Incidental Findings”). This outlines the process 
of involving a dedicated local hospital NHS consultant clinician in the case of a suspected abnormality, although 
it is stressed that a routine inspection and reporting of research scans is not carried out. In the case of a 
suspected abnormality, the Principal Investigator would alert our Contact Radiographer who, if appropriate (i.e. 
not a simple artefact) would independently inform the Contact Neurologist. They would in turn obtain the 
opinion of the Contact Neuroradiologist, and decide on the appropriate course of action, which might involve 
contact with the individual at the earliest opportunity and possible further investigation, including a hospital 
(NHS) diagnostic scan. This would all take place within the NHS framework and in communication with the 
volunteer’s GP.   
If a researcher has concerns that a volunteer may have an undiagnosed psychiatric condition that is causing 
distress (identified during the screening visit or following review of the mood-related questionnaires), CUREC 
guidance (BPG08) will be followed. The researcher will seek advice from the Principal Investigator who may 
discuss the symptoms in greater detail with the volunteer and/or offer the opportunity to speak with a senior 
clinical researcher. If the volunteer indicates that they are not currently receiving support and it is felt 
necessary, they will be encouraged to contact their General Practitioner. 
Please give details of departmental SOPs (if any) that will be followed in the case of an incidental finding 
During the consent process, participants would be informed of our standard procedure for incidental findings 
[APPENDIX I: WIN/OCMR/OHBA STANDARD OPERATING PROCEDURE (SOP) – DEALING WITH RESEARCH 
NEUROIMAGING INCIDENTAL FINDINGS].  
 

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d) Ethical Considerations 
Will you include any vulnerable participants (e.g. children, elderly)? 
If yes, please describe how they are defined as vulnerable and detail any CUREC 
approved procedures or guidance that you feel apply. 
Yes   
 
No   X 
 
Will taking part in the research put participants under any particular burden and/or 
risk? 
If yes, describe how this will be mitigated. 
Yes  X 
No   
 
a) There is a theoretical risk that a participant may have an adverse reaction to the study drugs. Participants will 
be informed of the potential side effects prior to taking the medication. To minimise risk, the participants’ 
general health will be assessed before being accepted into the study. They will be excluded from the study if 
they are currently taking any psychoactive medication or if they have any known contraindications to taking the 
drug (see exclusion criteria).  
 
The most frequently reported adverse reactions associated with prucalopride 2mg therapy are headache 
(17.8%) and gastrointestinal symptoms (abdominal pain (13.7%), nausea (13.7%) and diarrhoea (12.0%)). Other 
side effects associated with prucalopride are decreased appetite, dizziness, vomiting, flatulence, fatigue, and 
gastrointestinal sounds. The terminal half-life of prucalopride is about 1 day. There is less information about 
the side effect profile in healthy volunteers rather than patients, or after short-term prucalopride 1mg 
administration, although a single 1mg dose of prucalopride was well tolerated in our previous healthy 
volunteer study. The potential side effects are clearly stated in the Participant Information Sheet and 
researchers will discuss these with participants as part of the informed consent procedure.  
The drug has been tested in healthy volunteers in pharmacokinetic studies and to establish interactions with 
other drugs (for example, we know that prucalopride does not affect the pharmacokinetics of the oral 
contraceptive (9)).  
To minimise the risk associated with side effects, participants will be contacted on days 2 and 4 of the study 
week by a named researcher to check there are no concerns. All participants will have 24-hour contact details 
of a named researcher who they can contact during the study period. The named researcher will in turn contact 
a qualified medical doctor if necessary. In order to limit the risks associated with fatigue, during the week of 
prucalopride/placebo administration, participants will be advised not to drink alcohol, and not to carry out 
activities requiring full alertness if they are aware of any impairment. 
If judged necessary by the medical lead, the randomisation code will be broken for that individual by the 
medical supervisor and the participant will be advised to stop taking the medication and withdrawn from the 
study.  
b) While most people do not experience discomfort in an MRI environment, the enclosed space of the scanner 
can potentially feel uncomfortable. Discomfort from lying still for a long period of time will be minimised with 
comfortable padding and positioning. Whilst in the scanner, participants will be able to use the alarm button if 
they wish to communicate with the operator or to interrupt scanning. People with a history of severe 
claustrophobia would be excluded from participation in the study. All participants will be introduced carefully 
to the scanner and informed that they can terminate the scan session at any stage, should they wish to do so. 
Once inside the scanner, participants will be able to indicate if they wish the scanning to cease by squeezing a 
bulb placed in their hand, or by requesting verbally. As the MRI scanner is noisy, participants will be given 
earplugs to minimise the noise. 
MRI is a safe, non-invasive technique, which does not involve ionising radiation. Risks associated with the 

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magnetic field will be removed by excluding potential participants with ferromagnetic objects in their bodies 
(e.g., metal implants, vessel clips, shrapnel injuries) or with implanted devices, which may be damaged by the 
magnet (e.g., heart pacemakers). All people entering the scanning room will complete an MRI Screening safety 
questionnaire just before entering the scanner. 
 
Will the research involve deliberate deception of participants?  
If yes, justify why deception is used, describe deception and debriefing process, and 
include debriefing documents in the application 
Yes   
 
No  X 
 
Will any procedures affect your own physical and/or psychological safety as a 
researcher?  
If yes, describe how this will be mitigated. 
Yes   
 
No   X 
 
Does your research raise issues relevant to the Counter-Terrorism and Security Act (the 
Prevent Duty), which seeks to prevent people from being drawn into terrorism? 
If yes, please say how you plan to address any related risks.  Please see advice on this on 
our Best Practice Guidance Web Page. 
Yes   
 
No   X 
 
Please give details of any other ethical and/or safety considerations 
 
 
 
9. STATISTICS AND ANALYSIS 
Do you have a statistical plan? 
If no, please justify. 
Yes   X 
No   
 
The IBM SPSS statistical software will be use to analyse all behavioural data.  
Demographic and baseline measures will be analysed using independent t-tests.  
Mood, anxiety, and side effect measures will be analysed using repeated measures analysis of variance 
(ANOVA).  
Behavioural task results will be analysed using between-groups analysis of variance (ANOVA).  
Any significant interactions will be followed up using simple main effect analyses. When assumptions of 
equality of variances are not fulfilled, the Greenhouse-Geisser procedure will be used to correct the degrees of 
freedom. 
Analysis of fMRI endpoints will be completed using the FSL software package. 
Number of Participants 
50 healthy volunteers (25 per group) 

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Have you done a sample size calculation? 
If yes, please give details below 
If no, please give details to indicate you have considered the implications the selected 
sample size will have on the study outcome 
Yes   
 
No   
 
We will be using the Emotion Test Battery, which is a well validated set of emotional processing tasks that are 
sensitive to antidepressant effects.  On the facial expression recognition task, one of the main outcome 
variables is accuracy at recognising fearful facial expressions and a sample size of 25/group would give 0.9 
power to detect changes of the magnitude of those we have seen in a previous antidepressant healthy 
volunteer study [drug mean 10.64 (SD 9.77) vs. placebo mean 3.36 (SD 5.96) from Harmer et al 2004 Am J 
Psych; ref 6]. 
Analysis of Outcome Measures 
Data analysis will take place at the University of Oxford, Department of Psychiatry and will be undertaken by 
the research team under the supervision of the Principal Investigator. All data will be analysed using a 
between-groups analysis of variance (ANOVA). Analysis of fMRI endpoints will be completed using the FSL 
software package.  
Withdrawn participants’ data will not be included in the analysis.  
The primary outcome measures are performance (accuracy and reaction time) in a computer-based task of 
facial expression recognition (FERT), and performance on the auditory verbal learning task AVLT, compared 
between drug and placebo groups.  Secondary to this is the amygdala and hippocampal BOLD fMRI response to 
emotional faces and novel vs. repeated scenes respectively, reward sensitivity on the PILT, and number of 
positive and negative words correctly categorised, recalled, and recognised on emotional memory tasks. The 
tertiary outcome measures are reaction times to fearful vs. happy faces on the FDOT, BOLD fMRI response 
during resting state, performance (accuracy and reaction time) on the OMT task of visual short term memory, 
and relative/global cerebral blood flow using arterial spin labelling, all compared between those receiving drug 
and placebo.   
 
 
10. DATA MANAGEMENT 
Management and handling of personal data and special category data of human participants, either directly or 
via a third party, will need to comply with the requirements of the General Data Protection Regulation (GDPR) 
and the new Data Protection Act, as set out in the University’s Guidance on Data Protection and Research.  In 
answering the questions below, please also consider the points raised in the Data Protection Checklist. For 
advice on research data management and security, please consult with the University’s Research Data Team 
(researchdata@ox.ac.uk) and/or your local IT department and the University’s web pages on research data 
management. 
Will your research involve the collection of records of consent (e.g. written forms, audio-
recorded, or other recorded consent)?  
If ‘yes’, these will be classed as fully identifiable personal data (directly linked to an 
individual).  
 
Yes  
 
Will your research involve the collection of other personal data? 
Yes  
 
If ‘Yes’, specify in what form(s) this will be stored: 
 
 

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 Fully identifiable (directly linked to an individual) 
Yes  
 
 Pseudonymised (potentially identifiable as data may be attributed to an individual if 
linkage information can be accessed elsewhere by researchers) 
 
No  
 Fully anonymised (i.e. cannot be linked to an individual) 
 
No  
Will your research involve the collection of special category data? 
Yes  
 
If ‘Yes’, specify in what form(s) this will be stored: 
 
 
 Fully identifiable (directly linked to an individual) 
Yes  
 
 Pseudonymised (potentially identifiable as data may be attributed to an individual if 
linkage information can be accessed elsewhere by researchers) 
 
No 
 Fully anonymised (i.e. cannot be linked to an individual) 
 
No 
 
How will any personally identifiable data be 
collected, transferred and backed up? 
Personal data (screening information and consent forms) will 
be collected in paper form during the screening visit at the 
Neurosciences Building, Warneford Hospital. These paper 
documents will be transferred by the researcher to a locked 
filing cupboard in a neighbouring room in the Neurosciences 
Building for storage.  
Where, and for how long, will personally 
identifiable data be stored during and after the 
study? 
a) Screening information (name, age [years, months], 
contact details, medical history, psychiatric history).  This 
information will be in paper form and non-anonymised.  It 
will be stored securely in a locked filing cupboard in a room 
that is locked when unoccupied. Contact details of 
participants who consent to being contacted about future 
research will be stored on a database on University 
computers. 
b) Consent forms.  This information will be in paper form 
and non-anonymised. It will be stored securely in a locked 
filing cupboard in a room that is locked when unoccupied.  
To comply with the General Data Protection Regulation 
(GDPR) and the new Data Protection Act, personal data will 
be deleted as soon as possible after it is no longer needed 
for the study. 
Screening information will be destroyed once the data has 
been analysed and the results have been published, unless 
participants give consent to be re-contacted about studies 
for which they may be suitable, in which cases contact 
details will be retained.  
Consent forms will be kept for 10 years after the end of the 
study.  
If storing pseudonymised data, please confirm 
that identifiers will be held separately from the 
research data and linked through a unique 
study number.  
Each participant will be assigned a unique study number at 
screening. A key will link participants’ personal details to 
their unique study number. This document will be stored in 
the Research Masterfile in a lockable filing cabinet, separate 
from all research data. It will be destroyed along with 

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consent forms – 10 years after the end of the study.  
Who will have access to the personally 
identifiable data? If personally identifiable 
data is to be shared with another organisation, 
how will it be transferred/disclosed securely? 
Only named researchers will have access to participants' 
personal data. 
When and how will personally identifiable 
data be destroyed? 
Once the data has been analysed and the results have been 
published, screening information will be destroyed by 
shredding unless participants have consented for their 
contact details to be retained. Consent forms will be 
destroyed by shredding 10 years after the end of the study.  
Who will have access to the research data? 
Named researchers will have access to the research data. 
Direct access will be granted to authorised representatives 
from the University of Oxford for monitoring and/or audit of 
the study to ensure compliance with regulations. 
How will research data be stored? 
a) Questionnaire data.  Questionnaire data will be 
anonymised by a participant ID number and will not be 
linked with any personal identifiers.  Completed paper 
questionnaires will be stored securely in a locked filing 
cabinet in a room that is locked when unoccupied.  
Anonymised electronic questionnaire data will be stored on 
University computers in a secured building, and will be 
firewall and password protected. 
b) Computer-based tasks and fMRI data.  Computer-based 
tasks data will be anonymised by a participant ID number 
and will not be linked with any personal identifiers.  The 
electronic and imaging data will be stored on University 
computers in a secured building, and will be firewall and 
password protected. 
c) Personal information.  Personal information (contact 
details, consent forms) will be kept in a lockable filing 
cabinet with access only by the University researchers.  
Personal data may be retained after the end of the study for 
participants who have agreed to be contacted for future 
studies.  For volunteers who do not wish to be contacted for 
future studies, personally identifiable data will be shredded 
as soon as possible after the completion of the study and 
within one year of completing study analyses.   
d) Key linking codes to personal details.  This will be kept in 
a lockable filing cabinet with access only by the University 
researchers.   
How long will research data be stored for? 
Research data will be archived at the end of the study in the 
Neurosciences Building Warneford Hospital, or in the 
University of Oxford's offsite archive facility. It will be 
archived in anonymous form and will be stored for a 
minimum of 10 years. 
What will be done with the research data at 
the end of the storage period? 
At the end of the storage period, research data will be 
destroyed. 

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11. STUDY MONITORING AND OVERSIGHT 
Who will be responsible for day-to-day supervision of the study? 
Dr Susannah Murphy  
Give information about frequency of meetings that will be held to discuss progress/problems. Who will be 
present at the meetings? 
The study team will meet fortnightly to discuss progress with the project. The Principal Investigator and named 
researchers will be present in these meetings.  
 
12. ETHICAL AND REGULATORY CONSIDERATIONS 
Declaration of Helsinki 
The Investigator will ensure that this study is conducted in accordance with the principles of the Declaration 
of Helsinki. 
Approvals 
The protocol, informed consent form, participant information sheet and any proposed advertising material 
will be submitted to the Medical Sciences IDREC, and host institution for written approval. 
The Investigator will submit and, where necessary, obtain approval from the Sponsor and the above parties 
for all amendments to the original approved documents. 
Annual Progress Report 
The CI shall submit an Annual Progress Report to the Medical Sciences IDREC with a copy to CTRG. 
 
13. INSURANCE STATEMENT 
The University has a specialist insurance policy in place which would operate in the event of any participant 
suffering harm as a result of their involvement in the research (Newline Underwriting Management Ltd, at 
Lloyd’s of London). 
 
 

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14. DISSEMINATION AND FEEDBACK OF STUDY OUTCOMES 
It is anticipated that the results of the study will be disseminated through the usual scientific channels at the 
end of the study, including peer-reviewed publication and presentation at scientific conferences. Participants 
will be offered the opportunity to receive a brief report summarising the findings at the end of the study.  
 
15. REFERENCES 
(1) Moussavi et al (2007) Lancet 370: 851-859 
(2) Burbui Hotopf (2003) Br J Psychiatry 178: 129-144 
(3) Lucas et al (2007) Neuron 55: 712-725 
(4) Mendez-David et al (2014) Neuropsychopharmacology 39: 1366-1378  
(5) Harmer et al (2009) Brit J Psychiatry 195: 102-108 
(6) Harmer et al (2004) Am J Psychiatry 161 (7): 1256-63 
(7) Ma (2015). Molecular Psychiatry, 1–9. 
(8) Godlewska et al. (2016). Translational Psychiatry, 22-6. 
(9) Van de Velde et al (2013) Drugs R D 13 (1): 43–51 
 

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16. DECLARATIONS AND SIGNATURES OF RESEARCHERS 
 I/We, the researcher(s) agree: 
 To start this research study only after obtaining approval from MS IDREC/CUREC; 
 To carry out this research study only if funding is adequate to enable it to be carried out according to 
good research practice and in an ethical manner; 
 That it is the responsibility of the Principal Investigator to ensure that all researchers working on this 
project are qualified and either experienced, or have received appropriate ethical training, to conduct 
the research described; 
 To provide additional information as requested by MS IDREC/CUREC before approval is secured and 
as research progresses; 
 To maintain the confidentiality of all data collected from or about study participants; 
 To notify CTRG and MS IDREC in writing immediately of any proposed change which would increase 
the risks that any participant is exposed to and await approval before proceeding with the proposed 
change; 
 To notify CTRG and MS IDREC if the principal researcher on the study changes and supply the name of 
the successor; 
 To notify CTRG and MS IDREC in writing within seven days if any serious *adverse event* occurs in the 
course of research;  
 To use data collected only for the study for which approval has been given; 
 To grant access to data only to authorised persons; and 
 To maintain security procedures for the protection of personal data, including (but not restricted to): 
removal of identifying information from data collection forms and computer files, storage of linkage 
codes in a locked cabinet and password control for access to identified data on computer files. 
 
Principal Investigator (Name) 
 
Principal Investigator (Signature) 
 
Medically qualified collaborator (Name) 
 
Medically qualified collaborator (Signature) 
 
Student (Name) 
 
Student (Signature) 
 
 
 
17. ACCEPTANCE BY HEAD OF DEPARTMENT/FACULTY* 
*or other senior member of the department if the Principal Investigator is the head of department.  Example 
nominees include Deputy Head of Department, or, for student projects, Director of Graduate Studies. 

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 
I have read the research application named above. 
 
On the basis of the information available to me, I judge the Principal Investigator/Supervisor and 
student researcher (if applicable) to be aware of their ethical responsibilities in regard to this 
research. 
 
I am satisfied that the proposed project has been subject to appropriate peer review and is likely to 
contribute to existing knowledge and/or to the education and training of the researcher(s) and that 
it is in the public interest. 
 
Head of Department (Name) 
 
Head of Department (Signature) 
 
Date 
 
 
 
18. AMENDMENT HISTORY 
Amendment 
No. 
Protocol 
Version 
No. 
Date 
issued 
Author(s) of changes 
Details of Changes made 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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19. APPENDIX A: Study Adverts  
Web advert: 
Version 1: 15th March 2018. CUREC Ref: _____________ 
 
 
 
Healthy volunteers needed for emotional  
processing study 
 
“The effect of seven day prucalopride administration on emotional processing in 
healthy volunteers” 
 
Healthy volunteers are needed for a study investigating the effects of seven-day 
administration of the drug prucalopride on the processing of emotions. 
 
If you are healthy, aged 18-40 years, right-handed and have no history of a 
psychological disorder please contact us for more information. You will be asked 
questions about your medical history to check your suitability for an MRI scan.  
 
The study is run at the Department of Psychiatry, Warneford Hospital, University of 
Oxford, over 3 sessions. The study involves a screening visit, and taking the drug 
or placebo for 7 days. The second visit includes a brain scan using functional 
Magnetic Resonance Imaging (fMRI). MRI is a type of brain scan that allows us to 
see how the brain is organised, processes information, and performs skills like 
speech or memory. This scan is safe and does not involve any needles or 
injections. The third visit includes computer-based psychological tasks.  
 
PERL@psych.ox.ac.uk 
 
01865 _ _ _ _ _ _  
 
Time and reasonable travel expenses will be reimbursed. 
 
Central University Research Ethics Committee number: ___________ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Poster advert: 
 
 
Healthy volunteers needed for  
emotional processing study 
 
 “The effect of seven day prucalopride administration on emotional processing  
in healthy volunteers” 
 
We are looking for healthy volunteers aged 18-40 years, with no history of a psychological disorder, 
who are right-handed, for a study investigating the effect of the drug prucalopride on the processing of 
emotions. 
 
 You would be invited to the University of Oxford Department of Psychiatry, Warneford Hospital, for 
three sessions.  
 
 The first session would take approximately 2 hours, involving detailed questions to see if you are 
eligible to take part, including questions about your medical history to check your suitability for an MRI 
scan. You would be given seven days of either prucalopride or placebo to take home, plus full 
instructions of how and when to take the study medication, as well as the 24-hour contact details of a 
researcher.  
 
 You would be invited to a second session (lasting approximately 1.5 hours) on the sixth day, which 
would involve a brain scan using functional Magnetic Resonance Imaging (fMRI). MRI is a type of 
brain scan that allows us to see how the brain is organised, processes information, and performs skills 
like speech or memory. This scan is safe and does not involve any needles or injections. On the seventh 
day you would be invited to a third session (lasting approximately 2 hours), which would involve 
psychological tasks.   
 
Please contact us for more information if you are interested in participating. 
Time and reasonable travel expenses will be reimbursed. 
 
lucy.wright@psych.ox.ac.uk 
01865 618319 
 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional 
Processing Study 
lucy.wright@psych.ox.ac.uk 
Prucalopride Emotional    
Processing Study 
lucy.wright@psych.ox.ac.uk 

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20. APPENDIX B: Re-contact Email Template   
1	
Dear _______ ,  
 
We are emailing you because you indicated when taking part in a study at the 
University of Oxford Department of Psychiatry that you would be willing to be 
contacted about future studies that you may be suitable for. We are looking for 
right-handed healthy volunteers aged 18-40 years, with no history of a psychological 
disorder, to take part in a study entitled 'The effect of seven day prucalopride 
administration on emotional processing in healthy volunteers'. I have attached a 
Participant Information Sheet, which gives full details of what the study involves.   
 
The purpose of the study is to investigate how short-term administration of the drug 
prucalopride (a licensed drug usually used to treat chronic constipation) changes 
how the brain deals with emotional information. Our research has previously shown 
that established antidepressants affect how people think about emotional 
information. These effects have been found to predict whether the antidepressant 
will help people feel better in the long term. Prucalopride, like many established 
antidepressants, temporarily affects the function of a brain chemical called 
serotonin, but does so in a different way. We are going to investigate whether or not 
prucalopride also has effects on the way in which the brain processes emotional 
information, and will measure the effects if it does.   
 
If you would like to take part, you will be invited to the Department of Psychiatry, 
Warneford Hospital, for a screening visit (maximum 2 hours) where you will be asked 
to answer some questions about yourself, including questions about your medical 
history to check your suitability for an MRI scan. If you are eligible to take part, you 
will be given seven days of study medication to take home. On the sixth study day 
you will be asked to attend a research visit (approx. 1.5 hours) and have a brain scan 
using functional Magnetic Resonance Imaging (fMRI) to look at any effects of 
prucalopride on brain activity. MRI is a type of brain scan that allows us to see how 
the brain is organised, processes information, and performs skills like speech or 
memory. This scan is safe and does not involve any needles or injections. On the 
seventh day you will be asked to return for a second research visit (approx. 2 hours) 
where you will be asked to complete computerised psychological tasks measuring 
your reactions to emotional and non-emotional stimuli. You will be reimbursed for 
your time.  
 
Please read the attached information sheet, which gives you full details of the study. 
If you would like to take part, or if you have any questions, please get in touch.  
 
Best wishes,  
[Named Researcher], [Qualifications], [Job title] 
 
If you would no longer like to be contacted about studies please contact a researcher 
(Named Researcher: PERL@psych.ox.ac.uk, or the Principal Investigator Dr Susannah 
Murphy: susannah.murphy@psych.ox.ac.uk) and we will remove you from the list.  
	
	
 

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21. APPENDIX C: Screening Form  
 
 
 
SCREENING FORM: THE EFFECT OF SEVEN DAY PRUCALOPRIDE ADMINISTRATION 
ON EMOTIONAL PROCESSING IN HEALTHY VOLUNTEERS 
 
 
Participant ID: __________________  
Date (dd/mm/yy): __________________ 
 
 
Confidentiality explained:  
 
Informed Consent obtained:  
 
 
 
DEMOGRAPHICS: 
 
Participant name: __________________________________________________ 
 
Gender: __________________________________ 
 
Age (years, months): __________________________________  
 
Occupation: __________________________________ 
 
Telephone number: __________________________________ 
 
Address:___________________________________________________________________________
__________________________________________________________________________________
__________________________________________________________________________________
_____________________________ 
 
Email: ______________________________________________________________ 
 
 
Handedness:  Right   
 
Left  
 
First Language:  
 
    Fluent in English:   Yes 
 
No  
 
Smoke:     Yes                 _______ per day  
No  
 
Alcohol units/week: __________________ 
 

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Maximum units consumed on a single occasion: __________________ 
 
Average caffeinated drinks per day: __________________ 
 
 
Ethnicity:  Caucasian                         Education Level (obtained):  High School  
                              Black  
 
 
             6th form college /GNVQ 
 
          Hispanic  
 
 
                Undergraduate degree  
                              Asian  
 
 
                  Post graduate degree  
 
                Other  
 
 
PREVIOUS STUDIES: 
 
Has the participant taken part in any studies at the Departments of Psychiatry or Psychology before?  
 
Yes  
                         No 
 
Has the participant taken part in a study involving taking a drug or medicine before? (IMPORTANT: 3-
month washout needed)  
 
Yes  
                         No 
 
 
HEIGHT AND WEIGHT: 
 
Height (cm): ______________________ 
 
Weight(kg): ______________________ 
 
Body Mass Index: _________________ 
 
 
 
MEDICAL / SURGICAL HISTORY:  
 
Is the participant suffering from or have they ever suffered from any significant medical or surgical 
condition?  
 
Yes  
                         No 
 
Medical problem / condition 
Yes 
No 
History of seizures / epilepsy 
 
 
History of blackouts, fainting, or dizziness while standing 
 
 
Body Mass Index= Weight (kg)  x10,000 
(Height (cm))2  

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Kidney problems (hepatic / renal / urinary dysfunction) 
 
 
Liver problems (hepatitis, any chronic conditions) 
 
 
Cardiac or respiratory problems (palpitations/racing heart, 
asthma, dyspnoea, high blood pressure / hypotension, lung 
pains, persistent cough)  
 
 
Dyslexia or any other reading impairments 
 
 
Endocrine dysfunction (hormonal problems), diabetes, 
thyroid problems  
 
 
Autoimmune disorders 
 
 
Allergies (e.g. drugs, food intolerance like lactose 
intolerance)  
 
 
History of bleeding disorders (e.g. cutaneous bleeding, 
gynaecological bleeding)  
 
 
Skin or subcutaneous tissue disorders (e.g. rash, urticaria, 
purpura)  
 
 
Persistent headaches/migraines  
 
 
History of vision problems/difficulties  
 
 
 
If YES, list:  
 
Diagnosis 
Year of first diagnosis 
Resolved 
Ongoing 
 
 
 
 
 
 
 
 
 
Is the participant currently, or have they ever suffered from:  
 
 
A gastro-intestinal disorder:   
Yes  
 
No  
 
 
Irritable bowel syndrome (IBS): 
Yes  
 
No  
 
 
Is the participant lactose intolerant?  
Yes  
 
No  
 
Does the participant have, or have they ever had a known lactate deficiency or problem absorbing 
lactose / galactose / glucose?  
 
Yes  
                         No 
 
CURRENT / PRIOR MEDICATION:  
 
Is the participant currently taking any medication (prescribed / OTC / vitamin supplements)?  
Yes  
                         No 
 
 

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Has the participant taken any medication / drug in the month prior to the screening?  
 
Yes  
                         No 
 
Is the participant currently taking any street drugs? (e.g. cannabis, MDMA)  
 
Yes  
                         No 
 
Has the participant ever taken any street drugs?  
 
Yes  
                         No 
 
If YES:  
 
Drug name 
End date 
Frequency 
 
 
 
 
 
 
 
 
PERSONAL AND FAMILY PSYCHIATRIC HISTORY:  
 
Personal:  
 
Does the participant suffer from (or have they ever suffered from) any psychological or psychiatric 
difficulties? (e.g. depression / anxiety / EDs)  
 
Yes  
                         No 
 
Has the participant ever seen a psychologist / psychiatrist / counsellor in the past? (check for 
disorders linked to childhood e.g. ADHD, dyslexia)  
 
Yes  
                         No 
 
 
Family:  
 
Has anyone in the participant's close family seen a psychologist / psychiatrist / counsellor?  
Yes  
                         No 
 
If YES, circumstances: ___________________________________________________ 
_____________________________________________________________________ 
 

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PREGNANCY / BREASTFEEDING:  
 
Is the participant currently pregnant, trying to become pregnant, or breastfeeding?  
 
    Yes   
 
      No   
 
      NA  
 
MENSTRUAL CYCLE:  
 
Length of cycle: ______________________ 
 
Regular/irregular: ______________________ 
 
Date of last menstrual period: ______________________ 
 
Predicted date of next period: ______________________ 
 
STRUCTURED CLINICAL INTERVIEW FOR DSM-V AXIS 1 DISORDERS:  
 
Has the SCID been completed:  
Yes  
                  No 
 
Document any "YES" responses:  
 
 
 
 
 
 
 
 
Study medic: Name: _____________________ Signature: _____________________ 
 
 
 
 
 
 
 

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22. APPENDIX D: MRI Screening Form  
 
 
Version: Jan 2017 
        
                             
 
 
  
 
 
 
Volunteer name    _______________________________________________             Gender  _________   
Date of birth   ______________________             Weight  ___________  kg             Height  ___________  m 
Please carefully check the following. Some items can interfere with MR examinations and may be hazardous to 
your safety. Clearly mark your answer with a circle and add any relevant information. If you require additional 
space please use the back page and indicate you have done this. Your answers will be kept strictly confidential. 
 
IF YOU HAVE ANY QUESTIONS THEN PLEASE ASK US BEFORE YOUR SCAN 
Do you have a heart pacemaker or pacing wires? 
YES 
NO 
Have you had any heart surgery (e.g. coronary stent, PFO closure)? 
YES 
NO 
Have you had any surgery to your head (including eyes / ears / brain), neck or spine? 
YES 
NO 
Do you have any implanted devices (e.g. hydrocephalus shunt, nerve stimulator, cochlear 
implant, aneurysm clip, hernia mesh)? 
YES 
NO 
Have you had any operations involving metallic pins / plates / screws / wires? 
YES 
NO 
Have you had any surgical procedures or endoscopy in the last 6 weeks? (Please write below)  
 
 
 
YES 
NO 
Have you ever had any other surgical procedures of any kind? (Please write below)                      
 
 
 
YES 
NO 
Have you ever sustained any injuries involving metal to the eyes or other part of the body (e.g. 
from drilling, grinding or welding)? 
YES 
NO 
Have you ever had a serious accident (e.g. road traffic or industrial accident, explosion injury, 
shooting, shrapnel injury?) 
YES 
NO 
Have you ever had a fit or blackout, or do you suffer from epilepsy or diabetes? 
YES 
NO 
Do you have any of the following (if yes please circle):  
Body piercing, eye makeup,  
coloured contact lenses 
Hearing aid, wearable medical device 
(e.g. drug pump, glucose monitor) 
Tattoos (including cosmetic) 
 
Dentures, dental braces, 
dental implants  
Medicated skin patch (e.g. pain, HRT, 
nicotine, contraceptive) 
Artificial limb, prosthesis, 
splint, brace or support 
 
FOR WOMEN OF CHILDBEARING AGE: 
Do you have an IUD (coil)? 
YES 
NO 
Could you be pregnant? 
YES 
NO 
Are you wearing any clothing, including underwear, that contains metallic threads or has been 
silver impregnated (e.g. anti-microbial)? 
YES 
NO 
Do you understand that this is a research scan and is not useful for diagnosis? 
YES 
NO 
Have you removed your jewellery, hairgrips, hearing aids, watch, spectacles, keys and coins? 
YES 
NO 
 
  
IMPORTANT:  NO METAL OBJECTS TO BE TAKEN INTO THE MAGNET ROOM 
 
Volunteer/Guardian signature  __________________________       Date of study  _____________ 
 
Screened by (Print name)  ______________________       Signature  _______________________ 
 
MRI SCREENING FORM  
3T VOLUNTEER 
 
MRI SCREENING FORM  
3T VOLUNTEER 
 

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23. APPENDIX E: Participant Information Sheet (PIS)  
 

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Version 2: 5th June 2018. CUREC Ref: R57219/RE001 
 
3 
• You have any contradictions to MRI scanning (e.g. metal objects in your body, 
pacemakers, significant claustrophobia)  
 
 
What will happen in the study if I decide to take part?  
The study will involve three visits in total, all taking place at the Warneford Hospital, Oxford 
(see Figure 1: study timeline). You will be assigned by chance to receive 7 days of either 
prucalopride (1mg once a day; half the standard dose) or placebo. The study has a ‘double 
blind’ design meaning that neither you nor the researcher will know whether you are 
receiving the drug or the placebo. 
Figure 1. Study timeline  
The first visit is a 'Screening visit' at the University of Oxford Department of Psychiatry, 
Warneford Hospital, which will last approximately 2 hours. During this visit, a researcher 
will meet you to go over the information sheet and explain the procedures. If you are 
happy to continue, they will then ask you to sign a consent form. They will ask you some 
detailed questions to see if you are suitable to take part, including questions about: your 
current and past psychological wellbeing, past traumatic experiences and abuse, your 
medical history (including a measurement of your height and weight), any medication that 
you are currently taking, and your lifestyle (alcohol/caffeine consumption, smoking, 
recreational drug usage). You will be asked to complete an MRI safety questionnaire 
including questions about your medical history to check your suitability for an MRI scan. 
You will also be asked to complete questionnaire measures of psychiatric 
symptoms/distress. If you are female we will ask you to complete a urine pregnancy test, 
and we will ask you about your menstrual cycle in order to avoid scheduling testing in the 
premenstrual week. If you feel uncomfortable at any stage of this meeting, you would, of 
course, be free to decline to answer any of the questions or withdraw from the study. 
You will be asked to wait while a medical doctor involved in the study assesses your 
eligibility to take part in the study, which will take a maximum of 30 minutes. If you are 
suitable and are willing to proceed, we will randomly allocate you to receive either 
prucalopride or placebo. In the event that additional information must be provided in order 
to determine your eligibility, such as previous studies you may have taken part in, a 
maximum of four weeks may elapse between screening and allocation to prucalopride or 
placebo. If more than four weeks elapses, you will be asked to attend another screening 
visit to reassess your eligibility to take part. Once randomly allocated, you will be given 
seven days of the study medication to take home with you, plus full instructions of how 
and when to take them. During this week, we will phone you on days 2 and 4 to check that 
there are no concerns. You will be provided with the 24-hour contact details of a 
researcher who you can contact throughout the study if you have any concerns about 
 
 

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24. APPENDIX F: Informed Consent Form (ICF)  
 
 

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25. APPENDIX G: Study Questionnaires  
 
 
 
 
Edinburgh Handedness Inventory:  
Edinburgh Handedness Inventory 
 
Surname_________________________G iven Name_____________________________  
 
Date of 
Birth____________________________S ex____________________________________  
 
 
Please indicate your preferences in the use of hands in the following activities by 
putting + in the appropriate column.  Where the preference is so strong that you would 
never try to use the other hand unless absolutely forces to, put ++.  If any case you are 
really indifferent put + in both columns. 
 
Some of the activities require both hands.  In these cases the part of the task, or 
object, for which hand preference is wanted is indicated in brackets. 
 
Please try to answer all the questions, and only leave a blank if you have no 
experience at all of the object or task. 
 
 
Left 
Right 
1. Writing 
 
 
2. Drawing 
 
 
3.  Throwing 
 
 
4.  Scissors 
 
 
5.  Toothbrush 
 
 
6.  Knife (without fork) 
 
 
7.  Spoon 
 
 
8.  Broom (upper hand) 
 
 
9.  Striking Match (match) 
 
 
10.  Opening box (lid) 
 
 
 
 
 
i.  Which foot do you prefer to kick with? 
 
 
ii.  Which eye do you use when using only one? 
 
 
 
L.Q.                                        L eave the spaces blank                              D ECLE 
 
 
 

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Beck Depression Inventory (BDI):   
Participant ID: 
 
 
 
 
 
 
 
Date: 
 
             BECK INVENTORY 1996, A. T. Beck 
 
This questionnaire consists of 21 groups of statements.  Please read each group of statements 
carefully, then pick out the one statement in each group that best describes the way you have been 
feeling in the past two weeks including today. 
Circle the number beside the statement you have picked. If several statements apply equally well, 
circle that which has the highest number. Be sure that you do not choose more than one statement 
for any group. Be sure to read all the statements in each group before making your choice. 
 
1. 
0 
I do not feel sad 
 
1 
I feel sad much of the time 
 
2 
I am sad all of the time  
 
3 
I am so sad or unhappy that I can’t stand it 
 
2. 
0 
I am not discouraged about my future 
 
1 
I feel more discouraged about my future than I used to be 
 
2 
I do not expect things to work out for me 
 
3 
I feel my future is hopeless and will only get worse  
 
3. 
0 
I do not feel like a failure 
 
1 
I have failed more than I should have 
 
2 
As I look back, I see a lot of failures  
 
3 
I feel I am a total failure as a person 
 
4. 
0 
I get as much pleasure as I ever did from the things I enjoy  
 
1 
I don’t enjoy things as much as I used to 
 
2 
I get very little pleasure from the things I used to enjoy  
 
3 
I can't get any pleasure from the things I used to enjoy  
 
5. 
0 
I don’t feel particularly guilty 
 
1 
I feel guilt over many things I have done or should have done  
 
2 
I feel guilty most of the time 
 
3 
I feel guilty all of the time 
 
6. 
0  
I don’t feel I am being punished 
 
1 
I feel I may be punished 
 
2 
I expect to be punished 
 
3 
I feel I am being punished 
 
7. 
0 
I feel the same about myself as ever 
 
1 
I have lost confidence in myself  
 
2 
I am disappointed in myself 
 
3 
I dislike myself  
 
 
 
 
 
 
 
 

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Participant ID: 
 
 
 
 
 
 
 
Date: 
 
 
8. 
0 
I don’t critisize or blame myself more than usual  
 
1 
I am more critical of myself than I used to be 
 
2 
I critisize myself for all of my faults 
 
3 
I blame myself for everything bad that happens 
 
9. 
0 
I don’t have any thoughts of killing myself 
 
1 
I have thoughts of killing myself, but I would not carry them out 
 
2 
I would like to kill myself 
 
3 
I would kill myself if I had the chance 
 
10. 
0 
I don’t cry any more than I used to 
 
1 
I cry more than I used to 
 
2 
I cry over little things  
 
3 
I feel like crying, but I can't  
 
11. 
0. 
I am no more restless or wound up than usual  
 
1 
I feel more restless or wound up than usual 
 
2 
I am so restless or agitated that it's hard to keep still  
 
3 
I am so restless or agitated that I have to keep moving or doing things  
 
12. 
0 
I have not lost interest in other people or activities  
 
1 
I am less interested in other people or things than before  
 
2 
I have lost most of my interest in other people or things  
 
3 
It's hard to get interested in anything  
 
13. 
0 
I make decisions about as well as ever  
 
1 
I find it more difficult to make decisions than usual  
 
2 
I have much greater difficulty in making decisions than I used to   
 
3 
I have trouble making any decisions  
 
14. 
0 
I do not feel I am worthless  
 
1 
I don't consider myself as worthwhile and useful as I used to  
 
2 
I feel more worthless compared to other people  
 
3 
I feel utterly worthless  
 
 
 
 
 
 
15. 
0 
I have as much energy as ever  
 
1 
I have less energy than I used to have  
 
2 
I don't have enough energy to do very much  
 
3 
I don't have enough energy to do anything   
 
 
 
 
 
 
 
 

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Participant ID: 
 
 
 
 
 
 
 
Date: 
 
16. 
0 
I have not experienced any change in my sleeping pattern  
 
1a 
I sleep somewhat more than usual  
 
1b 
I sleep somewhat less than usual  
 
2a 
I sleep a lot more than usual  
 
2b 
I sleep a lot less than usual  
 
3a  
I sleep most of the day  
 
3b  
I wake up 1-2 hours early and can't get back to sleep  
 
17. 
0 
I am no more irritable than usual  
 
1 
I am more irritable than usual  
 
2 
I am much more irritable than usual 
 
3 
I am irritable all the time  
 
18. 
0 
I have not experienced any change in my appetite  
 
1a 
My appetite is somewhat less than usual  
 
1b 
My appetite is somewhat greater than usual  
 
2a 
My appetite is much less than usual 
 
2b 
My appetite is much greater than usual  
 
3a 
I have no appetite at all  
 
3b 
I crave food all the time   
 
 
 
 
 
19. 
0 
I can concentrate as well as ever  
 
1 
I can't concentrate as well as usual  
 
2 
It's hard to keep my mind on anything for very long  
 
3 
I find I can't concentrate on anything  
 
 
 
 
20. 
0 
I am no more tired or fatigued than usual  
 
1 
I get more tired or fatigued more easily than usual  
 
2 
I am too tired or fatigued to do a lot of the things I used to  
 
3 
I am too tired or fatigued to do most of the things I used to  
 
 
 
 
 
 
21. 
0 
I have not noticed any recent changes in my interest in sex 
 
1 
I am less interested in sex than I used to be 
 
2 
I am much less interested in sex now 
 
3 
I have lost interest in sex completely 
 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 54 of 86 
Eysenck Personality Questionnaire (EPQ):  
E.P.Q. (Adult) 
 
 
Name……………………………………………………… 
Occupation……………………………………………….. 
Age………………………..Sex………………………….. 
 
INSTRUCTIONS  Please answer each question by putting a circle 
around the “YES” or the “NO” following the question. There are no right 
or wrong answers, and no trick questions. Work quickly and do not 
think too long about the exact meaning of the questions. 
 
PLEASE REMEMBER TO ANSWER EACH QUESTION 
 
 
 
 
1. Do you have many different hobbies?  
 
 
 
 
YES    NO 
2. Do you stop to think things over before doing anything? 
 
 
YES    NO 
3. Does your mood often go up and down? 
 
 
 
 
YES    NO 
4. Have you ever taken the praise for something you knew someone else had 
really done? 
 
 
 
 
 
 
 
 
YES    NO 
5. Are you a talkative person? 
 
 
 
 
 
 
YES    NO 
6. Would you being in debt worry you?  
 
 
 
 
YES    NO 
7. Do you ever feel “just miserable” for no reason? 
 
 
 
YES    NO 
8. Were you ever greedy by helping yourself to more than your share 
 of anything? 
 
 
 
 
 
 
 
 
YES    NO 
9. Do you lock up your house carefully at night?  
 
 
 
YES    NO 
10. Are you rather lively? 
 
 
 
 
 
 
YES    NO 
11. Would it upset you a lot to see a child or an animal suffer? 
 
 
YES    NO 
12. Do you often worry about things you should not have done or said?  
YES    NO 
13. If you say you will do something, do you always keep your promise no matter 
how inconvenient it might be? 
 
 
 
 
 
 
YES    NO 
14. Can you usually let yourself go and enjoy yourself at a lively party? 
 
YES    NO 
15. Are you an irritable person?  
 
 
 
 
 
YES    NO 
16. Have you ever blamed someone for doing something you knew was really 
your fault? 
 
 
 
 
 
 
 
 
YES    NO 
17. Do you enjoy meeting new people?  
 
 
 
 
YES    NO 
18. Do you believe insurance schemes are a good idea?  
 
 
YES    NO 
19. Are your feelings easily hurt? 
 
 
 
 
 
YES    NO 
20. Are all your habits good and desirable ones?  
 
 
 
YES    NO 
21. Do you tend to keep in the background on social occasions?  
 
YES    NO 
22. Would you take drugs which may have strange or dangerous effects? 
YES    NO 
23. Do you often feel “fed-up”?  
 
 
 
 
 
YES    NO 
 
PLEASE TURN OVER  
 
Page 1 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 55 of 86 
24. Have you ever taken anything (even a pin or button) that belonged to  
someone else?  
 
 
 
 
 
 
 
YES     NO 
25. Do you like going out a lot?  
 
 
 
 
 
YES     NO 
26. Do you enjoy hurting people you love? 
 
 
 
 
YES     NO 
27. Are you often troubled about feelings of guilt? 
 
 
 
YES     NO 
28. Do you sometimes talk about things you know nothing about? 
 
YES     NO 
29. Do you prefer reading to meeting people? 
 
 
 
 
YES     NO 
30. Do you have enemies who want to harm you? 
 
 
 
YES     NO 
31. Would you call yourself a nervous person? 
 
 
 
 
YES     NO 
32. Do you have many friends?  
 
 
 
 
 
YES     NO 
33. Do you enjoy practical jokes that can sometimes really hurt people?  
YES     NO 
34. Are you a worrier?  
 
 
 
 
 
 
YES     NO 
35. As a child did you do as you were told immediately and without grumbling? 
YES     NO 
36. Would you call yourself happy-go-lucky? 
 
 
 
 
YES     NO 
37. Do good manners and cleanliness matter much to you? 
 
 
YES     NO 
38. Do you worry about awful things that might happen?  
 
 
YES     NO 
39. Have you ever broken or lost something belonging to someone else?  
YES     NO 
40. Do you usually take the initiative in making new friends? 
 
 
YES     NO 
41. Would you call yourself tense or “highly-strung”? 
 
 
 
YES     NO 
42. Are you mostly quiet when you are with other people? 
 
 
YES     NO 
43. Do you think marriage is old-fashioned and should be done away with? 
YES     NO 
44. Do you sometimes boast a little? 
 
 
 
 
 
YES     NO 
45. Can you easily get some life into a rather dull party?  
 
 
YES     NO 
46. Do people who drive carefully annoy you? 
 
 
 
 
YES     NO 
47. Do you worry about your health? 
 
 
 
 
 
YES     NO 
48. Have you ever said anything bad or nasty about anyone? 
 
 
YES     NO 
49. Do you like telling jokes and funny stories to your friends? 
 
 
YES     NO 
50. Do most things taste the same to you? 
 
 
 
 
YES     NO 
51. As a child were you ever cheeky to your parents? 
 
 
 
YES     NO 
52. Do you like mixing with people? 
 
 
 
 
 
YES     NO 
53. Does it worry you if you know there are mistakes in your work? 
 
YES     NO 
54. Do you suffer from sleeplessness?  
 
 
 
 
YES     NO 
55. Do you always wash before a meal?  
 
 
 
 
YES     NO 
56. Do you nearly always have a “ready answer” when people talk to you? 
YES     NO 
57. Do you like to arrive at appointments in plenty of time? 
 
 
YES     NO 
58. Have you often felt listless and tired for no reason?  
 
 
YES     NO 
59. Have you ever cheated at a game?  
 
 
 
 
YES     NO 
60. Do you like doing things in which you have to act quickly? 
 
 
YES     NO 
61. Is (or was) your mother a good woman? 
 
 
 
 
YES     NO 
 
Page 2 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 56 of 86 
62. Do you often feel life is very dull? 
 
 
 
 
 
YES     NO 
63. Have you ever taken advantage of someone? 
 
 
 
YES     NO 
64. Do you often take on more activities than you have time for?  
 
YES     NO 
65. Are there several people who keep trying to avoid you? 
 
 
YES     NO 
66. Do you worry a lot about your looks?  
 
 
 
 
YES     NO 
67. Do you think people spend too much time safeguarding their future with 
savings and insurances? 
 
 
 
 
 
 
YES     NO 
68. Have you ever wished that you were dead?  
 
 
 
YES     NO 
69. Would you dodge paying taxes if you were sure you could never be found  
out? 
 
 
 
 
 
 
 
 
 
YES     NO 
70. Can you get a party going?  
 
 
 
 
 
YES     NO 
71. Do you try not to be rude to people?  
 
 
 
 
YES     NO 
72. Do you worry too long after an embarrassing experience? 
 
 
YES     NO 
73. Have you ever insisted on having your own way? 
 
 
 
YES     NO 
74. When you catch a train do you often arrive at the last minute? 
 
YES     NO 
75. Do you suffer from “nerves”? 
 
 
 
 
 
YES     NO 
76. Do your friendships break up easily without it being your fault? 
 
YES     NO 
77. Do you often feel lonely? 
 
 
 
 
 
 
YES     NO 
78. Do you always practice what you preach? 
 
 
 
 
YES     NO 
79. Do you sometimes like teasing animals? 
 
 
 
 
YES     NO 
80. Are you easily hurt when people find fault with you or the work you do? 
YES     NO 
81. Have you ever been late for an appointment or work? 
 
 
YES     NO 
82. Do you like plenty of bustle and excitement around you? 
 
 
YES     NO 
83. Would you like other people to be afraid of you? 
 
 
 
YES     NO 
84. Are you sometimes bubbling over with energy and sometimes very sluggish? YES     NO 
85. Do you sometimes put off until tomorrow what you ought to do today? 
YES     NO 
86. Do other people think of you as being very lively? 
 
 
 
YES     NO 
87. Do people tell you a lot of lies? 
 
 
 
 
 
YES     NO 
88. Are you touchy about some things?  
 
 
 
 
YES     NO 
89. Are you always willing to admit it when you have made a mistake? 
 
YES     NO 
90. Would you feel very sorry for an animal caught in a trap? 
 
 
YES     NO 
 
 
 
 
 
PLEASE CHECK TO SEE THAT YOU HAVE ANSWERED ALL THE QUESTIONS 
 
 
 
Page 3 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 57 of 86 
State and Trait Anxiety Inventory (STAI):  
Participant ID 
 
Date 
TRAIT QUESTIONNAIRE 
 
A number of statements that people have used to describe themselves are given below.  Read 
each statement and then circle the appropriate number to the right of the statement to indicate 
how you GENERALLY feel.  There are no right and wrong answers.  Do not spend too much 
time on each statement but give the answer that seems to describe you best. 
 
Not at all 
Somewhat 
Moderately   Very much 
 
1. I feel pleasant 
 
 
1   
 
2 
 
3 
 
4 
 
2. I feel nervous and restless 
 
1 
 
2 
 
3 
 
4 
 
3. I feel satisfied with myself 
 
1 
 
2 
 
3 
 
4 
 
4. I wish I could be as happy 
as others seem to be 
 
 
1 
 
2 
 
3 
 
4 
 
5. I feel like a failure 
 
 
1 
 
2 
 
3 
 
4 
 
6. I feel rested  
 
 
1 
 
2 
 
3 
 
4 
 
7. I am ‘cool, calm and collected’ 
1 
 
2 
 
3 
 
4 
 
8. I feel that the difficulties are piling  
up so that I cannot overcome them 
1 
 
2 
 
3 
 
4 
 
9. I worry too much over something  
that doesn’t really matter 
 
1 
 
2 
 
3 
 
4 
 
10. I am happy  
 
 
1 
 
2 
 
3 
 
4 
 
11. I have disturbing thoughts 
 
1 
 
2 
 
3 
 
4 
 
12. I lack self-confidence 
 
1 
 
2 
 
3 
 
4 
 
13. I feel secure  
 
 
1 
 
2 
 
3 
 
4 
 
14. I make decisions easily 
 
1 
 
2 
 
3 
 
4 
 
15. I feel inadequate 
 
 
1 
 
2 
 
3 
 
4 
 
16. I am content 
 
 
1 
 
2 
 
3 
 
4 
 
17. Some unimportant thoughts run  
through my mind and bother me  
1 
 
2 
 
3 
 
4 
 
18. I take disappointments so keenly  
that I can’t put them out of my mind 
1 
 
2 
 
3 
 
4 
 
19. I am a steady person  
 
1 
 
2 
 
3 
 
4 
 
20. I get in a state of tension or  
turmoil as I think over recent  
concerns and interests  
 
1 
 
2 
 
3 
 
4 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 58 of 86 
Participant ID 
 
Date 
STATE QUESTIONNAIRE 
 
A number of statements that people have used to describe themselves are given below.  
Read each statement and then circle the appropriate number to the right of the statement 
to indicate how you feel RIGHT NOW, that is, AT THIS MOMENT IN TIME.  There 
are no right and wrong answers.  Do not spend too much time on each statement but give 
the answer that seems to describe your present feelings best. 
 
 
 
 
 
 
 
Not at all 
Somewhat 
Moderately   Very much 
 
 
 
 
 
 
 
 
 
 
 
 
1. I feel calm  
 
 
 
1 
 
2 
 
3 
        4 
 
2. I feel secure  
 
 
 
1 
 
2 
 
3 
        4 
 
3. I am tense  
 
 
 
1 
 
2 
 
3 
        4 
 
4. I feel strained 
 
 
 
1  
 
2 
 
3 
        4 
 
5. I feel at ease 
 
 
 
1  
 
2 
 
3 
        4 
 
6. I feel upset  
 
 
 
1 
 
2 
 
3 
        4 
 
7. I am presently worrying over 
possible misfortunes  
 
 
1 
 
2 
 
3 
        4 
 
8. I feel satisfied 
 
 
 
1 
 
2 
 
3 
        4 
 
9. I feel frightened 
 
 
 
1 
 
2 
 
3 
        4 
 
10. I feel comfortable  
 
 
1 
 
2 
 
3 
        4 
 
11. I feel self confident 
 
 
1 
 
2 
 
3 
        4 
 
12. I feel nervous 
 
 
 
1 
 
2 
 
3 
        4 
 
13. I am jittery 
 
 
 
1 
 
2 
 
3 
        4 
 
14. I feel indecisive 
 
 
 
1 
 
2 
 
3 
        4 
 
15. I am relaxed 
 
 
 
1 
 
2 
 
3  
        4 
 
16. I feel content 
 
 
 
1 
 
2 
 
3 
        4 
 
17. I am worried 
 
 
 
1 
 
2 
 
3 
        4 
 
18. I feel confused 
 
 
 
1 
 
2 
 
3 
        4 
 
19. I feel steady 
 
 
 
1 
 
2 
 
3 
        4 
 
20. I feel pleasant 
 
 
 
1 
 
2 
 
3 
        4 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 59 of 86 
Positive and Negative Affect Schedule (PANAS):  
 
Positive and Negative Affective Schedule (PANAS) 
                                                                                                                      
               
 
 
 
This scale consists of a number of words that describe different feelings and emotions. 
Please read each item and mark the appropriate answer in the space next to the word. 
Indicate to what extent you have felt this way today. 
 
 
1. Very slightly or not at all 
 
2. A little 
 
3. Moderately 
 
4. Quite a bit 
 
5. Extremely 
 
 
 
Interested 
 
____ 
 
 
 
 
Irritable 
____ 
 
Distressed 
 
____ 
 
 
 
 
Alert 
 
____ 
 
Excited 
 
____ 
 
 
 
 
Ashamed 
____ 
 
Upset 
 
____ 
 
 
 
 
Inspired 
____ 
 
Strong 
 
____ 
 
 
 
 
Nervous 
____ 
 
Guilty 
 
____ 
 
 
 
 
Determined 
____ 
 
 
Scared 
 
____ 
 
 
 
 
Attentive 
____ 
 
Hostile 
 
____ 
 
 
 
 
Jittery  
____ 
 
Enthusiastic  
____ 
 
 
 
 
Active  
____ 
 
Proud 
 
____ 
 
 
 
 
Afraid  
____ 
 
 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 60 of 86 
Snaith-Hamilton Pleasure Scale (SHAPS):  
SHAPS Questionnaire 
This questionnaire is designed to measure your ability to experience pleasure in the last few days. It is important 
to read each statement very carefully. Tick one of the boxes to indicate how much you agree or disagree with 
each statement. 
 
 
 
 
 
 
 
 
 
 
I would enjoy my favourite television programme 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly 
Agree 
I would enjoy being with my family or close friends 
 
Definitely 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
I would find pleasure in my hobbies and pastimes 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly 
Agree 
I would be able to enjoy my favourite meal 
 
 
Definitely 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
I would enjoy a warm bath or refreshing shower 
 
 
Definitely 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
I would find pleasure in the scent of flowers or the 
smell of a fresh sea breeze or freshly baked bread 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly 
Agree 
I would enjoy seeing other people’s smiling faces 
 
Definitely 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
I would enjoy looking smart when I have made an effort 
with my appearance 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly 
Agree 
I would enjoy reading a book, magazine or newspaper 
 
Definitely 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
I would enjoy a cup of tea or coffee or my favourite 
drink 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly 
Agree 
I would find pleasure in small things, e.g. bright sunny 
day, a telephone call from a friend 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly 
Agree 
I would be able to enjoy a beautiful landscape or view 
 
Definitely 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
I would get pleasure from helping others 
 
 
Strongly 
Disagree 
Disagree 
Agree 
Strongly 
Agree 
I would feel pleasure when I receive praise from other 
people 
 
Definitely 
Agree 
Agree 
Disagree 
Strongly 
Disagree 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 61 of 86 
National Adult Reading Test (NART):  
NART (2nd edition) 
 
CHORD 
 
 
 
 
 
 
 
SIMILE 
ACHE 
 
 
 
 
 
 
 
BANAL 
DEPOT 
 
 
 
 
 
 
 
QUADRUPED 
AISLE 
 
 
 
 
 
 
 
CELLIST 
BOUQUET  
 
 
 
 
 
 
FACADE 
PSALM 
 
 
 
 
 
 
 
ZEALOT 
CAPON 
 
 
 
 
 
 
 
GAUCHE 
 
DENY 
 
 
 
 
 
 
 
TOPIARY 
NAUSEA 
 
 
 
 
 
 
 
LEVIATHAN 
 
DEBT  
 
 
 
 
 
 
 
BEATIFY 
COURTEOUS 
 
 
 
 
 
 
PRELATE 
RAREFY 
 
 
 
 
 
 
 
SIDEREAL 
DRACHM   
 
 
 
 
 
 
EQUIVOCAL 
AEON 
 
 
 
 
 
 
 
NAIVE 
PLACEBO  
 
 
 
 
 
 
CATACOMB 
ABSTEMIOUS 
 
 
 
 
 
 
GAOLED 
 
DÉTENTE  
 
 
 
 
 
 
THYME 
IDYLL  
 
 
 
 
 
 
 
HEIR 
PUERPERAL  
 
 
 
 
 
 
RADIX 
AVER  
 
 
 
 
 
 
 
ASSIGNATE 
HIATUS  
 
 
 
 
 
 
 
DEMESNE 
SUBTLE 
 
 
 
 
 
 
 
SYNCOPE 
PROCREATE 
 
 
 
 
 
 
LABILE 
GIST   
 
 
 
 
 
 
 
CAMPANILE 
GOUGE 
SUPERFLUOUS 
 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 62 of 86 
Side Effect Questionnaire:  
Side Effects Questionnaire 
 
Please indicate the level at which you are currently experiencing the 
following by placing a tick in the appropriate box.  
 
 
SIDE EFFECT 
ABSENT 
MILD 
MODERATE SEVERE 
 
HEADACHE 
 
 
 
 
 
ABDOMINAL PAIN 
 
 
 
 
 
NAUSEA 
 
 
 
 
 
DIARRHOEA  
 
 
 
 
 
DECREASED 
APPETITE 
 
 
 
 
 
DIZZINESS 
 
 
 
 
 
VOMITING 
 
 
 
 
 
FLATULENCE 
 
 
 
 
 
FATIGUE 
 
 
 
 
 
GASTROINTESTINAL 
SOUNDS 
 
 
 
 
 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 63 of 86 
Visual Analogue Scales (VAS):  
Participant ID: _______________   
 
 
Date: _______________ 
 
 
•  Please indicate the extent to which you are currently experiencing each of the feelings below 
•  The line should be regarded as the full range of each feeling 
•  Mark your response with a perpendicular line: | 
 
 
Not at all  
 
 
 
        
 
             Extremely 
 
 
HAPPY 
 
 
 
 
 
 
SAD 
 
 
 
 
 
 
HOSTILE 
 
 
 
 
 
 
ALERT 
 
 
 
 
 
 
ANXIOUS 
 
 
 
 
 
 
CALM 
 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 64 of 86 
26. APPENDIX H: Encapsulation Standard Operating Procedure (SOP) 
 
Neurosciences  
SOP Number: Encapsulation Version 1: 30.05.2012 
 
 
 
Study Name:  
 
 
 
Ethics Number:  
 
 
 
Drug: 
 
 
 
Date:  
 
Drug and Placebo Capsule Preparation 
 
Purpose:  
This SOP provides a standardised checklist for the preparation of drug and placebo  
 
 
capsules for research studies carried out in Neurosciences 
 
Written by: 
Name:   
Ann Sharpley  
 
 
Signature:  
 
 
Date: 
 
Adapted by: 
Name:  
Clare Williams 
 
 
Signature: 
 
 
Date: 
 
 
Approved by:  Name:   
Philip Cowen 
 
 
Signature: 
 
 
Date:  
 
Approved by:  Name:   
Catherine Harmer 
 
 
Signature: 
 
 
Date: 
 
QP Approval:  Name:   
Michael Breese 
 
 
Signature: 
 
 
Date: 
 
 
 
Valid From:  
 
 
 
Issued to: 
Date: 
 
Process completed and approved 
 
Total number of pages: 16 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 65 of 86 
 
 
Section 1 
Documentation Preparation 
 
Responsibilities:  This SOP should always be carried out by 2 members of staff that have been trained in the 
following procedure and understand the principles of GMP. They will sign the delegation log for the study. 
 
Staff Member 1:    
 
 
Name:  
Signature: 
Initials  
Date: 
 
 
Staff Member 2:    
 
 
Name:  
Signature: 
Initials:  
Date: 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 66 of 86 
 
 
Section 2 
Room Preparations 
 
Room Location:  
 
 
 
Room G009 Research Kitchen 
 
Clothing: 
 
 
 
 
Lab coat and mop hat and latex free gloves 
 
Room Line Cleared (tidied,  
 
 
Sign: 
cleaned with disinfectant and  
anti bacterial wipes and free  
from all other materials) 
 
 
Date: 
 
 
 
 
From Stock  Prucalopride 2mg film-coated tablets 
 
 
Capsules:  
 
Location:  
 
 
 
Batch number:  
 
 
 
Expiry Date:  
 
Placebo: 
 
Location:  
 
 
 
Batch number:  
 
 
 
Expiry Date:  
 
Drug: 
 
 
Location:  
 
 
 
Batch number: 
 
 
 
Expiry Date: 
 
 
 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 67 of 86 
 
 
 
Section 3 
 
Placebo Capsule Preparation 
 
 
Date and Time Procedure Commenced: 
 
Number of placebo bottles to be made up today:  
 
Number of placebo capsules to be placed in bottle:  
 
Total number of placebo capsules to be made today:  
 
 
Checklist 
Procedure 
Action  
 
 
 
 
 
 
 
 
Clothing : 
Lab coat 
 
 
Mop hat 
 
 
Replace Latex free gloves after cleaning with new gloves  
 
 
Equipment: 
Place paper dressing on cleaned work surface 
 
 
Plastic trays x5 
 
 
Capsule Bases  
……………… 
 
 
Capsule Lids 
 
……………… 
 
 
Placebo Tablets  
……………… 
 
 
Plastic Bottles  
……………… 
 
 
Labels  
 
……………… 
 
 
 
 
 
 
 
Set up 
 
 
 
Staff member 1  
 
 
Initials: 
 
 
 
 
 
Count out required number of capsule bases 
 
 
Place in 1st tray 
 
 
Count out required number of placebo tablets 
 
 
Place in 2nd tray 
 
 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 68 of 86 
 
 
 
Staff member 2  
 
 
Initials:  
 
 
Date: 
 
 
 
Check number of capsules bases are correct 
 
 
Check number of placebo tablets are correct 
 
 
Count out required number of capsule lids 
 
 
Place in 3rd tray 
 
 
Place 4th tray next to 3rd tray 
 
 
Place 5th tray next to 4th tray 
 
 
Count out required number of plastic bottles 
 
 
Place plastic bottles next to 5th tray 
 
 
Place label sheet next to bottles 
 
 
Staff member 1  
 
 
Initials: 
 
 
 
Check number of capsules lids are correct 
 
 
Check number of plastic bottles are correct 
 
 
Complete first column of Section 4: reconciliation 
 
 
Place all excess products (capsules, placebo tablets, spare bottles)  
 
 
to one side away from assembly area 
 
 
Section 4 
 
 
 
 
Assembly 
 
 
 
 
Staff member 1  
 
 
Initials: 
 
 
 
 
 
Place each tablet into body of capsule base  
 
 
and pass this to Staff member 2 
 
 
 
 
Staff member 2  
 
 
Initials: 
 
 
 
Check that each passed capsule base contains a tablet 
 
 
Place a capsule lid firmly onto each capsule base 
 
 
Check that each completed placebo capsule is securely locked 
 
 
Place each placebo capsule into tray 4 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 69 of 86 
 
 
 
 
 
Completion: 
 
 
 
Once all completed placebo capsules have been placed onto  
 
 
tray 4 these can now be placed into the bottles 
 
 
Staff member 2  
 
 
Initials: 
 
 
 
Count the required number of placebo capsules for the 1st bottle onto tray 5 
 
Staff member 1  
 
 
Initials: 
 
 
 
Check the number of placebo capsules in tray 5 is correct 
 
 
And then place these into a plastic bottle and securely attach the lid 
 
 
 
Repeat this procedure for the required number of bottles 
 
 
Section 5  
 
 
 
Labelling: 
 
Staff member 2:  
 
 
Signed:  
 
 
Date: 
 
Place a sample label below:    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Attach a label onto each filled bottle and a sample label onto this sheet. Sign and date across the label/page. 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 70 of 86 
Section 6 
 
 
Reconciliation 
 
 
 
Completed by: 
Staff member 1  
Initials:  
 
 
 
Date: 
 
Checked by: 
Staff member 2  
Initials:  
Date: 
 
 
 
 
 
No. at start.  No. used.  No. rejected.  No. remaining.  % Reconciliation 
 
 
 
 
 
 
                                        
Capsule Bases 
 
 
Placebo tablets  
                                                                                            
 
Capsule Lids                                                                                                                
 
Completed placebo                                                                                          
Capsules  
 
Empty Plastic Bottles: 
 
 
Completed plastic bottles:    
 
Labels: 
 
Completed Plastic Bottles with Labels 
 
Reconciliation limits: 100% Placebo tablets, completed capsules and labels. 
 
 
 
100 +/-2% Capsule bases and lids, plastic bottles 
 
Reconciliation outside of the above limits must be investigated. 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 71 of 86 
 
Section 7 
 
Area Clear 
 
Completed by: 
Staff member 1  
Initials:  
 
 
 
Date: 
 
Checked by: 
Staff member 2  
Initials:  
Date: 
 
 
Completed labelled bottles of placebo to be placed in designated locked storage 
 
Location:  
 
Other items to be returned 
Placebo tablets 
Location: 
 
Reject and destroy excess Labels and remaining empty capsule lids and bases 
 
Confirm the area is completely clear of materials, product and documentation before processing to the next 
activity 
 
Place trays, paper sheet, mop hat and latex gloves in bin 
Ensure no other study material remains 
Return lab coats to hooks  
Return this completed batch record to the designated file 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
Date and time placebo preparation completed: 
 
 
Staff member 1  
 
 
Signed:  
 
Date: 
 
 
Time: 
Staff member 2  
 
 
Signed:  
 
Date: 
 
 
Time: 
 
 

CUREC 3 Protocol and Application Form Version 2.3.  Approved by CUREC 23 Feb 2017 
 
Page 72 of 86 
 
Section 8 
 
Room Preparation 
 
Room Location:  
 
 
Room G009 Research Kitchen 
 
Clothing: 
 
 
 
Lab coat and mop hat and latex free gloves 
 
Room Cleared (tidied,  
 
Sign: 
cleaned with disinfectant and 
anti bacterial wipes and free 
 
Date: 
from all other materials) 
 
From Stock 
 
Drug Capsule Preparation 
 
Capsules: 
 
Location: 
 
 
 
Batch Number: 
 
 
 
Expiry Date: 
 
Drug: 
 
 
Location: 
 
 
 
Batch Number: 
 
 
 
Expiry Date: 
 
Bottles:  
 
Location: 
 
 
 
Batch Number: 
 
 
 
Expiry Date: 
 
Labels:  
 
Location: 
 
 
 
Batch Number: 
 
 
 
 
 
 
 
Section 9 
 
Drug Capsule Preparation 
 
Date and Time Procedure Commenced: 
 
Number of drug bottles to be made up: 
 
Number of drug capsules to be placed in each bottle: 
 
Total number of drug capsules to be made: 
 
 
Checklist 

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Procedure 
Action  
 
 
 
 
 
 
 
 
Clothing : 
Lab coat 
 
 
Mop hat 
 
 
Replace Latex free gloves after cleaning with new gloves  
 
 
Equipment: 
Place paper dressing on cleaned work surface 
 
 
Plastic trays x5 
 
 
Capsule Bases  
……………… 
 
 
Capsule Lids 
 
……………… 
 
 
Drug Tablets 
      ………… 
 
 
Plastic Bottles  
……………… 
 
 
Labels  
 
……………… 
 
 
 
 
 
 
 
Set up 
 
 
 
Staff member 1  
 
 
Initials: 
 
 
 
 
 
Count out required number of capsule bases 
 
 
Place in 1st tray 
 
 
Count out required number of drug tablets 
 
 
Place in 2nd tray 
 
 
 
 

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Staff member 2  
 
 
Initials: 
 
 
 
Check number of capsules bases are correct 
 
 
Check number of drug tablets are correct 
 
 
Count out required number of capsule lids 
 
 
Place in 3rd tray 
 
 
Place 4th tray next to 3rd tray 
 
 
Place 5th tray next to 4th tray 
 
 
Count out required number of plastic bottles 
 
 
Place plastic bottles next to 5th tray 
 
 
Place label sheet next to bottles 
 
 
 
 
 
Staff member 1  
 
 
Initials: 
 
 
 
Check number of capsules lids are correct 
 
 
Check number of plastic bottles are correct 
 
 
Complete first column of Section 11: reconciliation  
 
 
Place all excess products (capsules, drug tablets, spare bottles) to one  
 
 
side away from assembly area 
 
 
Section 10 
 
 
 
 
Assembly 
 
 
 
 
Staff member 1  
 
 
Initials: 
 
 
 
 
 
Place each tablet into body of capsule base  
 
 
and pass this to Staff member 2 
 
 
 
 
Staff member 2  
 
 
Initials: 
 
 
 
Check that each passed capsule base contains a tablet 
 
 
Place a capsule lid firmly onto each capsule base 
 
 
Check that each completed drug capsule is securely  
 
 
locked 
 
 
Place each drug capsule into tray 4 
 

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Completion: 
 
 
 
Once all completed drug capsules have been placed onto  
 
 
tray 4 these can now be placed into the bottles 
 
 
Staff member 2  
 
 
Initials: 
 
 
 
Count the required number of drug capsules for the 1st bottle onto tray 5 
 
Staff member 1  
 
 
Initials: 
 
 
 
Check the number of drug capsules in tray 5 is correct 
 
 
and then place these into a plastic bottle and securely 
 
 
attach the lid 
 
 
 
Repeat this procedure for the required number of bottles 

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Section 11 
 
 
 
Labelling: 
 
Staff member 2:  
 
 
Signed:  
 
 
Date: 
 
Place a sample label below:    
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Attach a label onto each filled bottle and a sample label onto this sheet. Sign and date across the label/page. 
 
Section 12 
 
 
Reconciliation 
 
 
 
Completed by: 
Staff member 1  
Initials:  
 
 
 
Date: 
 
Checked by: 
Staff member 2  
Initials:  
Date: 
 
 
 
 
 
 
No. at start.  No. used.  No. rejected.  No. remaining.  % Reconciliation 
 
 
 
 
 
 
                                        
Capsule Bases 
 
 
Placebo tablets  
                                                                                            
 
Capsule Lids                                                                                                                
 
Completed placebo                                                                                          
Capsules  
 
Empty Plastic Bottles: 
 
 
Completed plastic bottles:    

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Labels: 
 
Completed Plastic Bottles with Labels 
 
Reconciliation limits: 100% Placebo tablets, completed capsules and labels. 
 
 
 
100 +/-2% Capsule bases and lids, plastic bottles 
 
Reconciliation outside of the above limits must be investigated. 

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Section 13 
 
Area Clear 
 
Completed by: 
Staff member 1  
Initials:  
 
 
 
Date: 
 
Checked by: 
Staff member 2  
Initials:  
Date: 
 
 
Completed labelled bottles of placebo to be placed in designated locked storage 
 
Location:  
 
Other items to be returned 
Placebo tablets 
Location: 
 
Reject and destroy excess Labels and remaining empty capsule lids and bases 
 
Confirm the area is completely clear of materials, product and documentation before processing to the next 
activity 
 
Place trays, paper sheet, mop hat and latex gloves in bin 
Ensure no other study material remains 
Return lab coats to hooks  
Return this completed batch record to the designated file 
 
 
 
Comments: 
 
 
 
 
 
 
 
 
 
Date and time Drug preparation completed: 01/02/2017 
 
 
Staff member 1  
Signed:  
 
Date:   
 
 
Time: 
Staff member 2  
Signed:  
 
Date:   
 
 
Time: 

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27. APPENDIX I: WIN/OCMR/OHBA Standard Operating Procedure (SOP) – 'Dealing 
With Research Neuroimaging Incidental Findings' 
STANDARD OPERATING PROCEDURE 
Dealing with Neuro Incidental Findings 
 
 
 
OHBA_014_V1 
OHBA, Department of Psychiatry 
FMRIB_002_V1 
FMRIB, Nuffield Department of Clinical Neurosciences 
Neuro_002_V5 
OCMR, Department of Cardiovascular Medicine 
 
 
 
 
Page 1 of 8 
 
 
 
 
 
 
 
 
SOP Number OHBA_014_V1 
FMRIB_002_V5 
Neuro_002_V5 
 
SOP Title 
Dealing with Research Neuroimaging Incidental Findings 
 
NAME  
TITLE 
SIGNATURE 
DATE 
Author 
Martin 
Turner  
Primary Contact 
Neurologist 
 
 
Author 
Pieter 
Pretorius  
Primary Contact 
Neuroradiologist  
 
 
Reviewer 
Stuart Clare 
Associate Professor, 
FMRIB 
 
 
Reviewer 
Clare 
Mackay 
Professor of Imaging 
Neuroscience 
 
 
Authoriser 
Heidi 
Johansen-
Berg 
Director, FMRIB 
 
 
 
 
 
 
 

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STANDARD OPERATING PROCEDURE 
Dealing with Neuro Incidental Findings 
 
 
 
OHBA_014_V1 
OHBA, Department of Psychiatry 
FMRIB_002_V1 
FMRIB, Nuffield Department of Clinical Neurosciences 
Neuro_002_V5 
OCMR, Department of Cardiovascular Medicine 
 
 
 
 
Page 2 of 8 
1. 
PURPOSE 
The purpose of this Standard Operating Procedure (SOP) is to describe the procedures to 
be followed if, in the course of neuroimaging for research protocols, an abnormal anatomy 
or pathology is detected.  In addition, written statements describing these procedures are 
provided as guidelines for inclusion in ethical applications. 
2. 
INTRODUCTION 
All volunteers giving consent to take part in neuroimaging studies are asked to indicate that 
they understand the scans will not be routinely formally reported by a radiologist, and that 
they are designed only to be used in research. Nonetheless, in the course of scanning 
subjects for research protocols, abnormal anatomy or pathology may be detected by a 
researcher or scan operator. 
The vast majority of such incidental findings require no specific action other than to inform 
the volunteer and their GP (so it can be noted on their medical record). However, 
regardless of its nature, the process of informing an individual about a possible abnormality 
is a highly sensitive one, that can lead to significant emotional distress if handled badly.  
This document summarises the FMRIB, OCMR and OHBA policies that have been agreed 
to address the occasional instances of abnormal anatomy or pathology (i.e., an incidental 
finding) being detected as part of a University of Oxford volunteer neuro research scan. 
The document also describes the procedures that should be followed when an abnormal 
neuro research scan is detected during any of the FMRIB, OCMR or OHBA magnetic 
resonance imaging sessions. Finally, the document also discusses the written statements 
that should be included with any ethics application at the time the application is made 
(Appendix 1). 
It should be noted that dealing with abnormal scans is an extremely sensitive issue, 
whether or not it has any further health implications, and needs to be dealt with in a very 
careful and methodical way. In particular, it is of paramount importance that the relevant 
research participant should not be unduly alarmed by the finding, and also that information 
about any subsequent interaction they may have with clinicians remains confidential and 
fully within their control in terms of any wider disclosure. To this end, a strict procedure 
(described herein) should be followed in the event that an incidental finding is noted and, 
importantly, the investigators/scan operators present when the scan is collected should 
not attempt to discuss anything with the participant during their scanning visit. Rather, it is 
necessary that the designated Contact Neurologist from whom advice is sought should 
form an opinion of the scan before the subject is contacted in any way about their scan. 
 
3. 
SCOPE 
This SOP relates to all neuro scans performed at FMRIB, OCMR or OHBA. 
4. 
DEFINITIONS 
PI=Principal Investigator 
5. 
RESPONSIBILITIES 
A list of individuals currently fulfilling the following roles is maintained on the FMRIB Website. 
 

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STANDARD OPERATING PROCEDURE 
Dealing with Neuro Incidental Findings 
 
 
 
OHBA_014_V1 
OHBA, Department of Psychiatry 
FMRIB_002_V1 
FMRIB, Nuffield Department of Clinical Neurosciences 
Neuro_002_V5 
OCMR, Department of Cardiovascular Medicine 
 
 
 
 
Page 3 of 8 
5.1 
Contact Radiographer 
A senior radiographer, who coordinates the recording and referral of the incidental finding to 
the Contact Neurologist. 
5.2 
Contact Neurologist 
A consultant neurologist with a local NHS contract, who, together with the Contact 
Neuroradiologist, determines if the incidental finding should be pursued.  Discusses the 
finding with the participant and assumes their NHS care if necessary. 
5.3 
Contact Neuroradiologist 
A consultant neuroradiologist with a local NHS contract, who, together with the Contact 
Neurologist, determines if the incidental finding should be pursued.  Specifies a scan protocol 
for follow up scans if required. 
6. 
SPECIFIC PROCEDURE 
6.1 
Procedure for dealing with an incidental finding on an MRI scan 
Note that an incidental finding may be detected either at the time the scan is collected or 
may be identified some time later, potentially months or even years later. Regardless, as 
soon as any abnormality is detected the following course of action should be followed: 
6.1.1 Any scan that raises cause for concern to an investigator or scan operator should, in the first 
instance, be shown to the Contact Radiographer as soon as practically possible after it is 
noticed. The investigator can then assume that the matter is dealt with, but should not expect 
further feedback on outcome to protect the confidentiality of the participant (whether or not 
the finding is significant). 
6.1.2 The Contact Radiographer will make an initial decision as to whether the abnormal finding is 
likely to be a scan artefact, or has already been referred. If the scan finding is determined to 
be artefact, or has been previously referred, then no further action will be taken, and the case 
will be considered closed. 
6.1.3 To ensure the outcome of all cases is clear and to prevent future duplicate referrals, the 
Contact Radiographer will track all referrals, whether or not they are passed on to the Contact 
Clinician, in an anonymised password-protected database that to which only they and the 
Contact Clinicians have access. Only the anonymised scan number, date of scanning, and 
findings are recorded. 
6.1.4 Once an incidental finding is suspected, the Contact Radiographer will inform the Contact 
Neurologist as soon as practically possible. For this purpose, the scans will be provided on 
CD-ROM in DICOM compliant electronic format (DICOM viewer software should be included 
on the CD-ROM). The CD-ROM will be labelled only with the anonymized scan number. A 
separate piece of paper is supplied (later securely disposed) with the name and date of birth 
of the participant plus the scan number to allow registration for the purposes of reporting by 
the Neuroradiologist. These records are NOT linked to any existing NHS records that a 
participant may have. It should be stressed that the participant should NOT be told anything 
about the referral or contacted at this point, and that the number of people involved in the 
overall process should be minimised.  
 

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STANDARD OPERATING PROCEDURE 
Dealing with Neuro Incidental Findings 
 
 
 
OHBA_014_V1 
OHBA, Department of Psychiatry 
FMRIB_002_V1 
FMRIB, Nuffield Department of Clinical Neurosciences 
Neuro_002_V5 
OCMR, Department of Cardiovascular Medicine 
 
 
 
 
Page 4 of 8 
6.1.5 The Contact Neurologist will arrange for the scans to be uploaded for viewing by the Contact 
Neuroradiologist. The Contact Neurologist and Contact Neuroradiologist will make a joint 
determination as to whether the incidental finding should be pursued, with a strong aim of 
avoiding participant ‘harm’ by only including those findings clearly known to be medically 
important. In the event that the incidental finding does not need to be pursued (usually a 
normal anatomical variant that does not need to be recorded with volunteer’s GP medical 
records) the database will be labelled as ‘no action necessary’, and the case will be closed.  
6.1.6 ‘Possibly significant’ findings include those without any future consequence that nonetheless 
need to be recorded on a volunteer’s medical record so that future healthcare professionals 
might know when it was first observed. This GP disclosure requires the consent of the 
volunteer, who must then have ultimate control over who else is informed. 
6.1.7 The Contact Neurologist will ask the Contact Radiographer to obtain a method of contact 
(ideally telephone) to discuss the scan findings. The Contact Neurologist may offer a formal 
consultation and physical examination at the earliest opportunity, depending on the nature of 
the finding. If so, then this will be done under the auspices of the NHS in a formal outpatient 
clinical setting. Whether or not a formal meeting is required, as a matter of standard clinical 
practice, the volunteer’s GP will be informed of the finding and any plan for further 
investigation or other recommendation in a letter from the Contact Neurologist (with the prior 
consent of the volunteer).  
6.1.8 The nature of the finding and any further action undertaken will be added to the anonymised 
database.  
6.1.9 The Contact Neurologist will explicitly advise all volunteers who have been contacted about 
their scans that it would be helpful if they let the official contact mentioned in the study’s 
Research Ethics Committee-approved Patient Information Sheet know about the finding. 
Additionally, they will be advised that they should NOT take part in any future neuroimaging 
research without disclosing the finding to the researcher beforehand. However, any decision 
to disclose personal health-related information (which may be highly sensitive) RESIDES 
WITH THE VOLUNTEER, and there must be no attempt by any researcher to ask either the 
subject or the Contact Radiographer to reveal the outcome of a current or previous referral. 
6.1.10 Although in some cases a researcher will be informed retrospectively by the volunteer of the 
outcome of an incidental finding (as advised by the Contact Neurologist), the decision on 
whether to remove a volunteer’s scan from a study lies with the PI and must be made without 
the expectation of automatic disclosure by the volunteer. In theory, a PI’s decision to remove 
a volunteer from a longitudinal study because of a significant structural abnormality risks 
indirect disclosure when the Contact Neurologist may not have deemed it necessary to 
contact the volunteer. In this rare circumstance, the PI should always inform the Contact 
Radiographer prior to telling a volunteer that they are being removed from further study, so 
that it is possible for the Contact Neurologist to make contact with the volunteer to reassure 
them. 
 
 
 
 

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STANDARD OPERATING PROCEDURE 
Dealing with Neuro Incidental Findings 
 
 
 
OHBA_014_V1 
OHBA, Department of Psychiatry 
FMRIB_002_V1 
FMRIB, Nuffield Department of Clinical Neurosciences 
Neuro_002_V5 
OCMR, Department of Cardiovascular Medicine 
 
 
 
 
Page 6 of 8 
b) Do NOT inform the subject of your suspicions or discuss the findings with anyone 
beyond the PI 
c) Do NOT ask the Contact Radiographer or participant later on to reveal the outcome 
of any further investigation that may (or may not) have taken place 
8. 
GUIDELINES ON VOLUNTEERS VIEWING THEIR SCANS 
8.1.1 Notes on Showing Scans to Subjects 
Under no circumstances should a volunteer research subject be confronted with an 
abnormal scan finding during their scanning visit. It is therefore recommended that subjects 
are not shown the images of their brains when they emerge from the scanner. Further, any 
promises to “show the subject their brain” should be avoided, both during volunteer 
recruitment and during the scan session itself. In the event that it is felt essential to show 
images to the volunteer, then only images that have been previewed by the scan operator 
should be shown. 
With regard to providing subjects with images of their brain to take away, some subjects 
may attempt to make “diagnoses” based on their scans, and will not be able to distinguish 
everyday scan artefacts (signal drop out, susceptibility distortions, flow artefacts etc.) from 
pathology.  Therefore, for many projects, it is inappropriate to provide subjects with images 
to take away in any form.  In the cases that subjects are provided with an image of their 
brain then only relatively low quality laser-printer images (possibly also pseudo-colour) 
should ever be provided. The following text should be appended to the bottom of the 
images: 
“These images are for illustrative purposes only.  They should not be used for diagnosis.” 
Electronic images should never be provided, other than to close collaborators on the 
project. In the event that a volunteer requests them under the Freedom of Information Act 
then this request should be referred via the appropriate University channels. 
8.1.2 Abnormalities Noted by Scan Operators During Volunteer Scanning 
If the scan operator notes an abnormality during the scan session (i.e. when the volunteer 
is still in the magnet) then extreme care should be taken to avoid alarming the volunteer. 
The acquisition of “special” additional scans should not be attempted. Instead, the 
procedures referred to earlier in this document should be followed. Also, in such 
circumstances, it is essential that the volunteer should not be shown their scans. 
9. 
GUIDELINES FOR WRITING ETHICS APPLICATIONS 
When writing your ethics application, there are a number of issues that should be 
addressed in the documentation that relate to the potential of abnormal scan findings. 
9.1.1 In the Patient Information Sheet that you write, it is recommended that the following text be 
included in the section titled ‘Are there any risks in taking part in this study?’: 
It is important to note that we do not carry out scans for diagnostic purposes, and therefore 
these scans are not a substitute for a doctor’s appointment.  Our scans are not routinely 
looked at by a doctor, rather our scans are intended for research purposes only. 
Occasionally a researcher may detect a possible abnormality. In this case, we would have 
the scan checked by a doctor.  If the doctor felt that the abnormality was medically 
 

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Page 85 of 86 
 
STANDARD OPERATING PROCEDURE 
Dealing with Neuro Incidental Findings 
 
 
 
OHBA_014_V1 
OHBA, Department of Psychiatry 
FMRIB_002_V1 
FMRIB, Nuffield Department of Clinical Neurosciences 
Neuro_002_V5 
OCMR, Department of Cardiovascular Medicine 
 
 
 
 
Page 7 of 8 
important, you would be contacted directly and recommended to have a hospital (NHS) 
diagnostic scan arranged. All information about you is kept strictly confidential.   
9.1.2 In the body of the application itself the following text is recommended: 
During the consent process, subjects would be informed of our standard procedure for 
incidental findings (“FMRIB/OCMR/OHBA SOP – Dealing with Incidental Findings”). This 
outlines the process of involving a dedicated local hospital NHS consultant clinician in the 
case of a suspected abnormality, although it is stressed that a routine inspection and 
reporting of research scans is not carried out. In the case of a suspected abnormality, the 
Principal Investigator would alert our Contact Radiographer who, if appropriate (i.e. not a 
simple artefact) would independently inform the Contact Neurologist. They would in turn 
obtain the opinion of the Contact Neuroradiologist, and decide on the appropriate course of 
action, which might involve contact with the individual at the earliest opportunity and 
possible further investigation. This would all take place within the NHS framework and in 
communication with the volunteer’s GP. 
9.1.3 It is recommended that the following statement is included in the Consent Form itself: 
“I understand that this is a research scan that is not useful for medical diagnosis, and that 
scans are not routinely looked at by a doctor. If a concern is raised about a possible 
abnormality on my scan, I will be informed if a doctor thinks it is medically important.” 
10. 
INTERNAL AND EXTERNAL REFERENCES 
University of Oxford Clinical Trials and Research Governance: 
http://www.admin.ox.ac.uk/researchsupport/ctrg/classification/ 
FMRIB Web Pages 
http://www.fmrib.ox.ac.uk/support 
OCMR Web Pages 
http://www.ocmr.ox.ac.uk/internal/information-for-researchers/ 
OHBA Webpages [insert link] 
 

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STANDARD OPERATING PROCEDURE 
Dealing with Neuro Incidental Findings 
 
 
 
OHBA_014_V1 
OHBA, Department of Psychiatry 
FMRIB_002_V1 
FMRIB, Nuffield Department of Clinical Neurosciences 
Neuro_002_V5 
OCMR, Department of Cardiovascular Medicine 
 
 
 
 
Page 8 of 8 
11. 
CHANGE HISTORY 
 
SOP no. 
Effective 
Date 
Significant Changes 
Previous 
SOP no. 
002-V1/ Neuro_002_V1 
(OCMR) 
1 October 
2007 
Formatted to new template. 
Slightly amended wording on giving scans to 
subjects. 
List of named contacts moved to website. 
Initial contact to be by clinician not researcher. 
May 2006 
002-V2/ Neuro_002_V2 
(OCMR) 
1st June 2011 Amended wording with regard to feedback 
and recording of outcome in scans referred. 
002-V1/ 
Neuro_002_V1 
(OCMR) 
002-V3/ Neuro_002_V3 
(OCMR) 
1st December 
2012 
Amended wording for subject information 
sheets. 
002-V2/ 
Neuro_002_V2 
(OCMR) 
002-V4/ Neuro_002_V4 
(OCMR) 
2nd February 
2014 
Amended wording with regard to feedback to 
the PI from the Contact Radiographer when 
no contact with the GP is needed 
Clarification of no feedback to researchers 
Clarified flowchart 
002-V3/ 
Neuro_002_V3 
(OCMR) 
FMRIB_002_V5 
Neuro_002_V5 
OHBA_014_V1 
15th July 2016 
OHBA added to SOP. Removed reference to 
supplying images as TIFF since all scanners 
now produce DICOM. 
002-V4/ 
Neuro_002_V4 
(OCMR)