The Effect of Seven-Day Atorvastatin Administration on Emotional Processing, Reward Processing, and Inflammation in Healthy Volunteers
Phase: NA
Conditions: Healthy
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. 
 
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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STUDY DETAILS 
Full Study Title 
The effect of seven-day atorvastatin administration on emotional processing, 
reward processing, and inflammation in healthy volunteers 
Internal Reference / Short 
title 
7-day atorvastatin and emotional processing 
MS IDREC Reference 
R61966/RE001 
Date and version number 
Version 1.0, 01st January 2019 
Principal Investigator 
Professor Phillip J Cowen 
MBBS, MD, FRCPsych 
phil.cowen@psych.ox.ac.uk 
01865 618311 
Department of Psychiatry, University of Oxford 
Student (if applicable) 
Doctor Riccardo De Giorgi 
MD, MRCPsych 
riccardo.degiorgi@bnc.ox.ac.uk 
01865 618238 
Department of Psychiatry, University of Oxford 
Graduate reading for DPhil in Biomedical and Clinical Sciences (Wellcome Trust 
Doctoral Training Fellow) 
University email contact 
phil.cowen@psych.ox.ac.uk 
riccardo.degiorgi@bnc.ox.ac.uk 
University telephone 
contact 
01865 618311 
01865 618238 
 

 
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Medically qualified 
collaborator (Licensed 
Doctor) 
Professor Phillip J Cowen 
MBBS, MD, FRCPsych 
phil.cowen@psych.ox.ac.uk 
01865 618311 
Department of Psychiatry, University of Oxford 
 
Doctor Riccardo De Giorgi 
MD, MRCPsych 
riccardo.degiorgi@bnc.ox.ac.uk 
01865 618238 
Department of Psychiatry, University of Oxford 
Graduate reading for DPhil in Biomedical and Clinical Sciences (Wellcome Trust 
Doctoral Training Fellow) 
Sponsor 
The University of Oxford 
External Funding 
Wellcome Trust, reference: 102176/Z/13/Z 
Will you submit or have you submitted this study to another ethics committee? 
Yes   
 
No   
 
If other relevant approvals for this research are required (e.g. from other universities’ ethics committees) please 
attach them and give more details below:  
 
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 J Harmer 
Department/Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study 
Professor of Cognitive Neuroscience 
DPhil, MA, DipLATHE 
Professor Harmer will be involved in the study design and interpretation of data 

 
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Professor Harmer has >20 years of 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 
Mr Nicola Rizzo 
Department/Institute 
name 
Department of Psychiatry, University of Oxford 
Role in Study 
Medical student 
Mr Rizzo will be involved in the recruitment, screening, and testing of participants 
Training/Qualification in 
Research Ethics 
28th December 2018: Good Clinical Practice (Medical Research Council online) 
 
 
 

 
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1. TABLE OF CONTENTS 
 
1. TABLE OF CONTENTS .......................................................................................................................................... 4 
2. SYNOPSIS ............................................................................................................................................................ 5 
3. ABBREVIATIONS .................................................................................................................................................. 6 
4. BACKGROUND AND RATIONALE ......................................................................................................................... 7 
5. PARTICIPANTS ..................................................................................................................................................... 8 
6. STUDY PROCEDURES ........................................................................................................................................ 10 
7. INTERVENTION(S) ............................................................................................................................................. 13 
a) 
Drug/Substance 1 ........................................................................................................................................ 13 
b) 
Drug/Substance 2 (or placebo) ................................................................................................................... 14 
8. SAFETY .............................................................................................................................................................. 15 
a) 
Definitions ................................................................................................................................................... 15 
b) 
Reporting Procedures for Serious Adverse Events or Reactions ................................................................ 15 
c) 
Safety of Participants .................................................................................................................................. 16 
d) 
Ethical Considerations ................................................................................................................................. 17 
9. STATISTICS AND ANALYSIS................................................................................................................................ 19 
10. DATA MANAGEMENT ....................................................................................................................................... 20 
11. STUDY MONITORING AND OVERSIGHT ............................................................................................................ 22 
12. ETHICAL AND REGULATORY CONSIDERATIONS ............................................................................................... 22 
Declaration of Helsinki ......................................................................................................................................... 22 
Approvals .............................................................................................................................................................. 22 
Annual Progress Report ........................................................................................................................................ 23 
13. INSURANCE STATEMENT .................................................................................................................................. 23 
14. DISSEMINATION AND FEEDBACK OF STUDY OUTCOMES ................................................................................ 23 
15. REFERENCES...................................................................................................................................................... 23 
16. DECLARATIONS AND SIGNATURES OF RESEARCHERS ...................................................................................... 25 
17. ACCEPTANCE BY HEAD OF DEPARTMENT/FACULTY* ...................................................................................... 25 
18. AMENDMENT HISTORY .................................................................................................................................... 26 
 
 
 
 

 
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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 of an Investigative Medicinal Product as we are not 
investigating the efficacy of atorvastatin but using it as a pharmacological tool to 
understand the role of inflammation in emotional and reward 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 
Neurosciences Building, Department of Psychiatry, University of Oxford, Warneford 
Hospital, Warneford Lane, Oxford, OX3 7JX 
Age Range of Study 
Participants 
18-50 years old 
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 February 2019 
Anticipated End 
Date 
1st February 2021 
 
Objectives 
Outcome Measures 
Primary 
 
To investigate the effects of seven-day 
atorvastatin 
administration 
on 
emotional processing 
Accuracy and reaction times on computer-
based tasks of emotional processing (e.g. facial 
expression 
recognition, 
emotional 
categorisation and memory), comparing those 
receiving drug and placebo. 
Secondary 
 
 
 
 
To investigate the effects of seven-day 
atorvastatin administration on reward 
processing 
 
Accuracy and reaction times on computer-
based tasks of reward processing comparing 
those receiving drug and placebo. 
 

 
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To investigate the effects of seven-day 
atorvastatin 
administration 
on 
inflammation 
Changes in high sensitivity-C Reactive Protein 
(hs-CRP) 
from 
baseline 
to 
seven-day, 
comparing those receiving drug and placebo 
Name of 
drug/substance 
Atorvastatin 
Purpose of 
drug/substance 
use in this study 
Work in our group has revealed that short-term (7-day) administration of antidepressants 
produces positive biases in the processing of emotional information in healthy volunteers. 
Such effect might be an important neuropsychological mechanism of antidepressant 
action.  
The current study will investigate the effect of seven-day administration of atorvastatin 
20mg on emotional and reward processing tasks in healthy volunteers. There is evidence 
that statins may exert antidepressant effects via anti-inflammatory and anti-oxidant 
pathways, and it is therefore predicted that atorvastatin will have positive effects on 
emotional and reward processing. 
Adverse reactions 
and side effects 
posing a particular 
risk with this 
treatment 
Muscle pain or weakness: usually mild and quickly responding to stopping or switching 
medication 
Elevation of liver transaminases: significant only in case of pre-existing hepatic disease 
Rhabdomyolysis: very rare but severe myopathy associated with elevated creatine kinase 
and myoglobinuria 
Nasopharyngitis, epistaxis, pharyngo-laryngeal pain: usually mild and quickly responding 
to stopping or switching medication 
Headache: usually mild and quickly responding to stopping or switching medication 
Gastrointestinal disturbances (constipation, diarrhoea, flatulence, dyspepsia, nausea): 
usually mild and quickly responding to stopping or switching medication 
New-onset diabetes mellitus: in predisposed individual with pre-existing hyperglycaemia 
Haemorrhagic stroke: in patients with prior haemorrhagic stroke or lacunar infarct 
 
 
3. ABBREVIATIONS 
 
BMI 
Body Mass Index 
CTRG 
Clinical Trials & Research Governance, University of Oxford 
CUREC 
Central University Research Ethics Committee 
DSM-5 
Diagnostic and Statistical Manual of Mental Disorders-5 
ETB 
Emotional Test Battery 
GP 
General Practitioner 
hs-CRP 
high sensitivity-C Reactive Protein 

 
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MS IDREC 
Medical Sciences Inter-Divisional Research Ethics Committee 
PIL 
Probabilistic Instrumental Learning 
SCID-5 
Structured Clinical Interview for DSM-5 
SOP 
Standard Operating Procedure 
 
 
4. BACKGROUND AND RATIONALE 
Depression is common and associated with considerable health disability (Kassebaum-2016). Traditional 
antidepressants mainly work by modulating monoamine levels in the synaptic cleft (Harmer-2017); however, the 
evidence that depression is caused by impaired serotonin or noradrenaline activity is weak and inconsistent 
(Cowen-2015), and indeed current antidepressant strategies remain burdened by partial efficacy, poor side-effects 
profile, and a slow onset of therapeutic action (Penn-2012). Therefore, there is a pressing need to develop 
antidepressant medications with novel non-monoaminergic mechanisms of action (Jha-2018) – or, conversely, to 
identify alternative pathophysiological pathways leading to depression that can be targeted with new drugs. 
Intriguingly, there is growing evidence that both peripheral and central inflammation play a role in the 
pathophysiology of depression (Miller-2017). 
Patients with depression consistently show negative biases in emotional processing, which are believed to play a 
key role in the aetiology and maintenance of their clinical symptoms (Roiser-2013). Overall, robust evidence 
suggests that early changes in emotional processing can serve as valid surrogate markers of antidepressant 
efficacy (Harmer-2017); for example, seven days’ treatment with selective serotonin and noradrenaline reuptake 
inhibitors (citalopram and reboxetine respectively) compared to placebo decreases the recognition of negative 
facial expressions and recall of negative versus positive stimuli in healthy volunteers (Harmer-2004). Conversely, 
another study using the pro-inflammatory cytokine interferon-α showed that inflammatory-mediated depression 
can be associated with an increased recognition of negative facial expressions (Cooper-2017). Furthermore, 
depression associated with inflammation is characterised by significant symptoms of anhedonia (Miller-2017), 
which has been linked to diminished neural responses to reward anticipation (Felger-2017). Such reward-deficit is 
particularly refractory to conventional serotoninergic and noradrenergic antidepressants (McCabe-201), and even 
the antidepressant bupropion (a noradrenaline and dopamine reuptake inhibitor), whilst inducing positive 
changes in emotional processing, appears to worsen reward processing (Walsh-2018). However, the reversal of 
this deficit in reward processing is still considered as a valuable marker of target engagement for anti-
inflammatory drugs in depression, as a more sensitive outcome measure than traditional rating scales designed 
to capture the global clinical symptomatology (Miller-2017). 
The 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors or statins are recommended and have been widely used 
since the ‘80s for the primary and secondary prevention of cardiovascular diseases (NICE 2014). It is now 
established that these medications have significant anti-inflammatory effects that are independent from their 
lipid-lowering properties (Jain-2005), as well as appearing early in treatment only after seven day of administration 
(Macin-2011). Statins are considered extremely safe drugs: their more common side-effect are muscle pain or 
weakness (usually mild and quickly responding to stopping or switching medication) and elevation of liver 
transaminases (significant only in case of pre-existing hepatic disease), whereas more serious adverse events 
include rhabdomyolysis (very rare but severe myopathy associated with elevated creatine kinase and 
myoglobinuria), new-onset diabetes mellitus (in predisposed individual with pre-existing hyperglycaemia), and 
haemorrhagic stroke (in patients with prior haemorrhagic stroke or lacunar infarct); however, clinical trials have 
ultimately concluded that such adverse events attributed to statin therapy in routine practice are not actually 

 
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caused by it (Collins-2016), especially at doses lower than 80mg/day and when used for less than 52 weeks (Li-
2016). Other common (≥ 1/100, < 1/10) but usually mild side-effects include: nasopharyngitis, pharyngo-laryngeal 
pain, epistaxis, headache, and gastrointestinal disturbances (constipation, diarrhoea, flatulence, dyspepsia, 
nausea). Importantly, a potential antidepressant effect for statins has been confirmed in animals (Kilic-2012), as 
well as clinically in observational (Parsaik-2014) and interventional studies (Salagre-2016). Although their anti-
inflammatory and anti-oxidant properties have been involved, the mechanisms underlying the antidepressant 
effects of statins remain unclear, therefore further translational studies have been advocated in order to elucidate 
this aspect (Köhler-Forsberg-2017).  
In this exploratory study, we will investigate the effect of seven-day administration of atorvastatin 20mg once 
daily compared to placebo on emotional and reward processing tasks in 50 healthy volunteers. In view of the 
previous evidence that statins may exert antidepressant effects via anti-inflammatory and anti-oxidant pathways, 
we predict that atorvastatin will have positive effect on emotional and reward processing. 
 
5. PARTICIPANTS 
Description of Study Participants 
50 healthy volunteers aged 18-50 years 
Inclusion Criteria 
• 
Male or female  
• 
Aged 18-50 years  
• 
Sufficiently fluent English to understand and complete the tasks  
• 
Body Mass Index in the range of 18-30 
• 
Participant is willing and able to give informed consent for participation in the study 
• 
Not currently taking any regular medications (except the contraceptive pill) 
Exclusion criteria 
The participant may not enter the study if any of the following apply: 
• 
Currently any regular medications (except the contraceptive pill) 
• 
History or current significant psychiatric illness 
• 
Current alcohol or substance misuse disorder 
• 
History or current significant hepatic disease 
• 
History or current significant neurological condition (e.g. epilepsy) 
• 
Known hypersensitivity to the study drug (i.e. atorvastatin) 
• 
Pregnant, breast feeding, women of child-bearing potential not using appropriate contraceptive measures 
• 
Participation in a study that uses the same or similar 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 
Recruitment 

 
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Participants will be recruited by word of mouth, emails to departmental mailing lists (sent by who usually has 
access to those mailing lists on our behalf), and posters located in University Departments. Moreover, we will 
use adverts (APPENDIX A: STUDY ADVERTS) sent to Junior Common Rooms and Middle Common Rooms, 
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 will 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 previous studies 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 Neurosciences Building, 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 they have. The researcher will then take written consent from the participant. All of 
the named researchers have been trained in taking informed consent. 
Screening and Eligibility Assessment 
Informed Consent will be obtained at the start of the screening, prior to the administration of questionnaires or 
the Structured Clinical Interview for DSM-5 disorders. 
A maximum of four weeks will be allowed between screening and randomisation to atorvastatin 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 
(using Structured Clinical Interview for DSM-5) will be taken (APPENDIX C: SCREENING FORM). Female 
participants will also have a urine pregnancy test. 
Information Provided to Participants and Informed Consent 
The Participant Information Sheet (APPENDIX D: PARTICIPANT INFORMATION SHEET) will be presented to the 
participants, in written 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 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 
(APPENDIX E: INFORMED CONSENT FORM) before any study specific procedures are performed. Written 

 
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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. A copy of the signed 
Informed Consent Form will be given to the participant. The original signed form will be retained at the study 
site.  
Participant Confidentiality 
The study staff will ensure that the participants’ data are safeguarded.  The study will comply with the Data 
Protection Act, which requires personal data to be anonymised as soon as it is practical to do so.  Where possible, 
participants will be identified only by a participant ID number on study documents and on any electronic 
database.  Documents (such as consent forms) that contain identifying data and/or information allowing this to 
be linked to the participant ID will be stored separately under strict access controls.  All documents will be stored 
securely and only accessible by study staff and authorised personnel. 
It will be 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 
will 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”.  
 
 
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) at the Neurosciences Building, Warneford Hospital.  
 
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  
• 
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-5 interview (Structured Clinical Interview for DSM-5) to probe for current or past psychiatric illness 
• 
Urine pregnancy test (female participants only) 
 
The following baseline assessments will be completed (APPENDIX F: QUESTIONNAIRES): 
• 
Beck Depression Inventory (BDI) 
• 
Eysenck Personality Questionnaire (EPQ) 

 
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• 
Positive and Negative Affect Schedule (PANAS) 
• 
Side-effects questionnaire (to determine baseline of bodily symptoms/’side-effects’) 
• 
Snaith-Hamilton Pleasure Scale (SHAPS) 
• 
State and Trait Anxiety Inventory (STAI) 
• 
Visual Analogue Scales (VAS) measuring subjective state 
Also, phlebotomy will be undertaken to obtain a sample of: 
• 
high sensitivity-C Reactive Protein 
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 to receive either 7-day atorvastatin 20mg (25 participants), or 7-day 
placebo (25 participants) administration. Randomisation will occur on the day of screening, or up to a maximum 
of 4 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 case, 
if more than 4 weeks have elapsed, another Screening Visit will be performed to ensure participants are still 
eligible. The randomisation code will be drawn up by a researcher not involved in the study using an online 
randomisation tool (https://www.sealedenvelope.com/simple-randomiser/v1/lists). Randomised participants 
will be given 7 days of the drug to take home, as well as full instructions of how and when to take them. 
The atorvastatin drug and the placebo will be provided by the Oxford Pharmacy Stores and will be encapsulated 
at the Neurosciences Building according to previously agreed standard operating procedures (APPENDIX G: 
Neurosciences, SOP Number: Encapsulation Version 2: 22.10.2012). Blinding will be achieved by the identical 
matching of the atorvastatin and placebo treatments. Participants will not be aware of the treatment that they 
will be receiving; neither will the researcher, as this study is double-blind. 
Allocation of treatments will be recorded on a Randomisation List, which will be updated when each new 
participant enters the randomised phase. The list will be held at the Neurosciences Building by a scientist 
uninvolved in the study. 
The study medication and placebo will be stored in a secure environment at the Neurosciences Building 
accessible only to staff. It will be stored at room temperature and accounted for using agreed study 
documentation. Using the Randomisation List and the participant’s unique randomisation code, staff will 
determine whether to dispense active or placebo tablets. 
The randomisation code will be broken if a participant requires treatment for a new medical condition or 
experiences serious adverse reactions and either of these situations make it clinically important to know what 
medication they are taking. A 24/7 emergency mobile contact number will be provided on a wallet-sized card 
given to participants during their Research Visit. The research team member on-call will be able to contact the 
medical supervisor and they will make the decision to unblind. In order to unblind the participant, the medic will 
access the list kept in a secure cabinet at the Neurosciences Building and will disclose the allocation within a 
maximum of one hour. If breaking the code is necessary, only the individual’s code will be broken. Data from 
unblinded participants will not be admitted to analysis. If unblinding occurs, the researcher will record the reason 
and result of the unblinding, as well as the date and time of the event. 
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, 

 
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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 
The Research Visit (approximately 2 hours) will take place after day 7 of atorvastatin/placebo administration. 
This visit will involve administration of behavioural tasks measuring emotional and reward processing. It will 
take place at the Neurosciences Building, Warneford Hospital. 
Participants will complete the following questionnaires before the behavioural tasks:  
• 
Positive and Negative Affect Schedule (PANAS)  
• 
Side-effects questionnaire 
• 
State Anxiety Inventory (state-STAI)  
• 
Visual Analogue Scales (VAS)  
Also, phlebotomy will be repeated to obtain a sample of: 
• 
high sensitivity-C Reactive Protein 
The behavioural tasks will include the Oxford Emotional Test Battery (ETB), which has previously been found to 
be sensitive to the effects of antidepressants, and a reward task of 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 7-day administration of atorvastatin/placebo. 
  
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 
Blood samples (4mL = i.e. 1 teaspoon) taken during the Screening Visit and the Research Visit for investigating 
hs-CRP will be handled at the Neurosciences Building’s laboratory. On the same day, they will be rendered 
acellular by centrifugation on receipt and stored at -30oC until assay. Any excess material remaining at the end 
of the study will be disposed of by the laboratory within 6 months according to the Human Tissue Authority 
guidelines. The samples will be stored in a freezer at the Neurosciences Building in an anonymised form. Access 
to the samples will be by the research team and the samples will be in the custody of Prof Philip Cowen who will 
hold the key code linking the samples to a particular individual. The samples will be analysed for once all 
participants have completed the study. 
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 

 
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• 
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 Informed 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 the 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 
Participants will be paid £100 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 
Atorvastatin 
Formulation and route of administration for 
study 
20mg atorvastatin tablets will be encapsulated in opaque 
capsules 
Dose and route of administration for study 
20mg atorvastatin once daily at night-time, oral dose  
Duration of treatment for study 
7 days 
Licence status of this drug/substance 
Atorvastatin is a licensed drug 
Usual Indication 
Atorvastatin is usually indicated in adult patients with primary 
hypercholesterolaemia, 
or 
combined 
(mixed) 
hyperlipidaemia in adult patients who have not responded 
adequately to diet and other appropriate measures, in adult 
patients with homozygous familial who have not responded 
adequately to diet and other appropriate measures, and in 
adult patients with atherosclerotic cardiovascular disease or 
diabetes mellitus for prevention of cardiovascular events 
Usual Dose 
10-80mg once daily, at night-time 

 
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Usual duration of treatment 
Life-long 
Where will drug/substance be sourced from? 
Oxford Pharmacy Stores 
Where will drug/substance be stored? 
Atorvastatin will be stored within the Neurosciences Building, 
Warneford Hospital. It will be stored at room temperature in 
a locked cupboard, which is suitable for drug storage. 
How will drug/substance be dispensed? 
Atorvastatin will be dispensed from the Neurosciences 
Building, Warneford Hospital by a study medic or nurse. 
How will the drug/substance be prepared by 
the researchers for use in this study? 
Atorvastatin will be encapsulated by trained clinical trial 
support staff using our Standard Operating Procedure 
(APPENDIX G: ENCAPSULATION STANDARD OPERATING 
PROCEDURE). 
 
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 once daily at night-time, oral dose  
Duration of treatment for study 
7 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 will be stored within the Neurosciences Building, 
Warneford Hospital. It will be stored at room temperature in 
a locked cupboard, which is suitable for drug storage. 
How will drug/substance be dispensed? 
Placebo will be dispensed from the Neurosciences Building, 
Warneford Hospital by a study medic or nurse. 
How will the drug/substance be prepared by 
the researchers for use in this study? 
Placebo will be encapsulated by trained clinical trial support 
staff using our Standard Operating Procedure (APPENDIX G: 
ENCAPSULATION STANDARD OPERATING PROCEDURE). 
 
 

 
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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 
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 

 
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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. 
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-5 interview (Structured Clinical Interview for DSM-5) 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) 
• Side-effects 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) 
Also, phlebotomy will be undertaken to obtain a sample of: 
• 
high sensitivity-C Reactive Protein 
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 the week of drug/placebo 
administration, 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? If not, please justify 
Participants’ GPs will not be informed about their participation in the study. Seven days of atorvastatin 20mg 
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, women of 
child-bearing potential not using appropriate contraceptive measures, or people who have any medical 
conditions for whom the study would not be suitable. 
What is your planned procedure if an incidental finding is suspected? 
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’s training will also be adhered to. 
If an incidental finding has clinical implications, what action will you take? 
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 GP. 
Please give details of departmental SOPs (if any) that will be followed in the case of an incidental finding 
As above. 
 
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   
 
 
Will taking part in the research put participants under any particular burden and/or 
risk? 
If yes, describe how this will be mitigated. 
Yes   
 
No   
 
The study will involve phlebotomy. Common risks associated with phlebotomy are pain during the procedure and 
bruising with associated pain afterwards. Less common risks include dizziness and the potential for fainting 
during the procedure. To minimise these risks, the staff undertaking the procedure will be fully trained in 
phlebotomy. Bruising after the event will also be reduced by promptly applying pressure on the puncture site 

 
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after the needle is withdrawn. All participants will be fully informed about these risks in the Participant 
Information Sheet. 
 
There is a theoretical risk that a participant may have an adverse reaction to the study drug. 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 regular medications (except the contraceptive pill) or if they have any known 
contraindications to taking the drug (see exclusion criteria). 
Statins are considered extremely safe drugs: their more common side-effect are muscle pain or weakness (usually 
mild and quickly responding to stopping or switching medication) and elevation of liver transaminases (significant 
only in case of pre-existing hepatic disease), whereas more serious adverse events include rhabdomyolysis (very 
rare but severe myopathy associated with elevated creatine kinase and myoglobinuria), new-onset diabetes 
mellitus (in predisposed individual with pre-existing hyperglycaemia), and haemorrhagic stroke (in patients with 
prior haemorrhagic stroke or lacunar infarct); however, clinical trials have ultimately concluded that such adverse 
events attributed to statin therapy in routine practice are not actually caused by it (Collins-2016), especially at 
doses lower than 80mg/day and when used for less than 52 weeks (Li-2016). Other common (≥ 1/100, < 1/10) 
but usually mild side-effects include: nasopharyngitis, pharyngo-laryngeal pain, epistaxis, headache, and 
gastrointestinal disturbances (constipation, diarrhoea, flatulence, dyspepsia, nausea). The potential side-effects 
and adverse events will be clearly stated in the Participant Information Sheet and researchers will discuss these 
with participants as part of the informed consent procedure. 
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 
statin/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. 
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   
 
 
Will any procedures affect your own physical and/or psychological safety as a 
researcher?  
If yes, describe how this will be mitigated. 
Yes   
 
No   
 
 
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   
 
 

 
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Please give details of any other ethical and/or safety considerations 
None 
 
 
9. STATISTICS AND ANALYSIS 
Do you have a statistical plan? 
If no, please justify. 
Yes   
 
No   
 
The IBM SPSS statistical software will be used to analyse all behavioural data. Demographic and baseline 
measures will be analysed using independent t-tests. 
Mood, anxiety, side-effects, and hs-CRP 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. 
Number of Participants 
50 healthy volunteers (25 per group) 
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 Oxford Emotional 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 per 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) (Harmer-2004). 
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). 
Withdrawn participants’ data will not be included in the analysis. 
The primary outcome measure is performance (accuracy and reaction time) in computer-based tasks of 
emotional processing in the comparison between drug and placebo groups. Secondary to this is performance 
(accuracy and reaction time) in a computer-based task of reward processing in the comparison between drug and 
placebo groups, and changes in high sensitivity-C Reactive Protein (hs-CRP) from baseline to seven-day in the 
comparison between drug and placebo groups. 
 
 

 
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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  
No  
Will your research involve the collection of other personal data? 
Yes  
No  
If ‘Yes’, specify in what form(s) this will be stored: 
 
 
• Fully identifiable (directly linked to an individual) 
Yes  
No  
• Pseudonymised (potentially identifiable as data may be attributed to an individual if 
linkage information can be accessed elsewhere by researchers) 
Yes  
No  
• Fully anonymised (i.e. cannot be linked to an individual) 
Yes  
No  
Will any of the personal data that you collect classify as special category data? 
Yes  
No  
If ‘Yes’, specify in what form(s) this will be stored: 
 
 
• Fully identifiable (directly linked to an individual) 
Yes  
No  
• Pseudonymised (potentially identifiable as data may be attributed to an individual if 
linkage information can be accessed elsewhere by researchers) 
Yes  
No 
• Fully anonymised (i.e. cannot be linked to an individual) 
Yes 
No 
 
How will any personally identifiable data be 
collected, transferred and backed up? 
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 collected 
by the study staff and 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. 
Consent forms. This information will be in paper form and 
non-anonymised. It will be collected by the study staff and 
stored securely in a locked filing cupboard in a room that is 
locked when unoccupied. 
Where, and for how long, will personally 
identifiable data be stored during and after 
the study? 
Screening information. Screening information will be kept in a 
lockable filing cabinet with access only by the University 
researchers. For volunteers who do not wish to be contacted 

 
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for future studies, screening information (including contact 
details) will be stored for up to one year of completing study 
analyses. Contact details may be retained after the end of the 
study for participants who have agreed to be contacted for 
future studies. 
Consent forms will be kept in a lockable filing cabinet with 
access only by the University researchers 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.  
Key linking codes to personal details. Key linking codes to 
personal details will be kept in a lockable filing cabinet with 
access only by the University researchers. They will be stored 
for up to one year of completing study analyses, and then 
destroyed by shredding 
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' 
personally identifiable data. 
When and how will personally identifiable 
data be destroyed? 
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. For volunteers who do not wish to be 
contacted for future studies, screening information (including 
contact details) will be stored for up to one year of completing 
study analyses, and then destroyed by shredding. Contact 
details may be retained after the end of the study for 
participants who have agreed to be contacted for future 
studies.  
Consent forms. Consent forms will be kept for 10 years after 
the end of the study, and then destroyed by shredding. 
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? 
Questionnaire 
data. 
Questionnaire 
data 
will 
be 
pseudonymised with a key linking code. Paper questionnaires 
will be stored securely in a locked filing cabinet in a room that 
is locked when unoccupied. Electronic questionnaire data will 
be stored on University computers in a secured building and 
will be firewall and password protected. 
Blood samples. Blood samples (4mL = 1 teaspoon) taken 
during the Screening Visit and the Research Visit for 
investigating hs-CRP will be handled at the Neurosciences 
Building’s laboratory. On the same day, they will be rendered 
acellular by centrifugation on receipt and stored at -30oC until 
assay. Any excess material remaining at the end of the study 
will be disposed of by the laboratory within 6 months 
according to the Human Tissue Authority guidelines. The 

 
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samples will be stored in a freezer at the Neurosciences 
Building in a pseudonymised form with a key linking code. 
Access to the samples will be by the research team and the 
samples will be in the custody of Prof Philip Cowen who will 
hold the key code linking the samples to a particular 
individual. The samples will be analysed for once all 
participants have completed the study. 
Computer-based tasks. Computer-based tasks data will be 
pseudonymised with a key linking code. Electronic data will be 
stored on University computers in a secured building and will 
be firewall and password protected. 
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. 
 
 
11. STUDY MONITORING AND OVERSIGHT 
Who will be responsible for day-to-day supervision of the study? 
Professor Philip J Cowen, Doctor Riccardo De Giorgi 
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 weekly 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(s) for written approval. 

 
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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. 
 
 
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). 
 
 
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. It will also form part 
of a DPhil dissertation and will comply with the Departmental policy on publications. 
Participants will be offered the opportunity to receive a brief report summarising the findings at the end of the 
study. 
 
 
15. REFERENCES 
Collins R, et al. Lancet. 2016 Nov 19; 388(10059):2532-2561. doi: 10.1016/S0140-6736(16)31357-5 
Cooper CM, et al. Psychological Medicine 2017; Page 1 of 10. doi:10.1017/S00332917170023792017 
Cowen PJ & Browning M. World Psychiatry 2015 Jun; 14(2): 158–160. doi: 10.1002/wps.20229 
Felger J, et al. Neuropsychopharmacology Reviews 2017; 42, 216–241. doi: 10.1038/npp.2016.143 
Harmer CJ, et al. Am J Psychiatry 2004; 161:1256–1263. doi: 10.1176/appi.ajp.161.7.1256 
Harmer CJ, et al. Lancet Psychiatry 2017 May; 4(5): 409–418. doi:10.1016/S2215-0366(17)30015-9 
Jain MK & Ridker PM. Nat Rev Drug Discov 2005 Dec; 4(12):977-87. doi: 10.1038/nrd1901 
Jha MK & Trivedi MH. Int. J. Mol. Sci. 2018; 19:233. doi:10.3390/ijms19010233 

 
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Kassebaum NJ, et al. Lancet 2016; 388(10053):1603-1658. doi: 10.1016/S0140-6736(16)31460-X 
Kilic FS, et al. Neurosciences (Riyadh). 2012 Jan; 17(1):39-43 
Köhler-Forsberg O, et al. CNS Drugs. 2017 May;31(5):335-343. doi: 10.1007/s40263-017-0422-3 
Li H, et al. Drug Saf. 2016 May; 39(5):409-19. doi: 10.1007/s40264-016-0394-0. 
Macin SM, et al. Am Heart J. 2005 Mar; 149(3):451-7. doi: 10.1016/j.ahj.2004.07.041 
McCabe C, et al. Biol Psychiatry. 2010 Mar 1; 67(5): 439–445. doi: 10.1016/j.biopsych.2009.11.001  
Miller AH, et al. Neuropsychopharmacology Reviews 2017;42:334–359. doi: 10.1038/npp.2016.229 
NICE. NICE Clinical Guidelines 2014; 181:11. Available from: https://www.ncbi.nlm.nih.gov/books/NBK268908/ 
Parsaik AK, et al. J Affect Disord. 2014 May; 160:62-7. doi: 10.1016/j.jad.2013.11.026 
Penn E, et al. Ther Adv Psychopharmacol 2012; 2(5):179–188. doi: 10.1177/ 2045125312445469 
Roiser JP & Sahakian J. CNS Spectrums 2013; 18:139–149. doi:10.1017/S1092852913000072 
Walsh AEL, et al. Front Psychiatry 2018 Oct 16; 9:482. doi: 10.3389/fpsyt.2018.00482 
Salagre E, et al. J Affect Disord. 2016 Aug; 200:235-42. doi: 10.1016/j.jad.2016.04.047 
 
 

 
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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) 
Professor Philip J Cowen 
Principal Investigator (Signature) 
 
Medically qualified collaborator (Name) 
Doctor Riccardo De Giorgi 
Medically qualified collaborator (Signature) 
 
Student (Name) 
Doctor Riccardo De Giorgi 
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. 

 
The effect of seven-day atorvastatin administration on emotional processing, reward processing, and inflammation in healthy volunteers 
MS IDREC reference: R61966/RE001; Version 1.0, 01st January 2019  
     Page 26 of 26 
• 
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