University of oxford

UNIVERSITY OF OXFORD
Participant Information Sheet

The effects of short term diazepam treatment on emotional processing in healthy volunteers
You are being invited to take part in a research project. Before you decide whether to take part it is
important for you to understand why the research is being done and what it will involve. Please take
time to read this information carefully and discuss it with friends, relatives and your GP if you wish.
If there is anything you do not understand, or if you would like more information, please ask us. Take
time to decide whether you wish to take part.
PART 1

What is the purpose of the study?
We are interested in finding out about how the brain deals with emotional and non emotional
information. It is known that certain drugs, for example antidepressants, can change the way we
process emotions. In this study, we are interested in looking at the effects of an anxiety reducing drug
called diazepam (sometimes called valium). We wish to find out whether changes in the processing
of emotional and non emotional information occur and to measure them if they do. This could allow
us to understand more about the way emotions work in the brain, and could also provide us with
ways of detecting the possible effects of new drugs on mood.
In order to study the effects of the drug, we will be using a number of computerized psychological
tests designed to measure your reactions to various stimuli. In addition, we would like to consider
the effects of the drug on brain responses to emotional information and so we will also be conducting
a functional magnetic resonance imaging (fMRI) scan.
Why have I been invited?
We are sending you this information sheet because you have either responded to an advertisement for
the study or because you have previously expressed an interest in hearing about studies that are
running in the department (please do let us know if this is no longer the case). You have been invited
to take part because you are currently healthy and aged 18-55. We hope to include 60 healthy
volunteers in the study. We are not able to include volunteers with a history of mental health
problems such as depression or anxiety.
Exclusion Criteria

In order to take part in this study, you must be fluent in English. This is due to the nature of some of the tasks we use. Further details will be given at the screening visit. You will not be able to take part in the study if you suffer from dyslexia. You will not be able to take part in this study if you currently suffer from, or have a history of, any mental health problems, such as depression, anxiety or an eating disorder, or if you suffer from any medical conditions. You will not be able to take part in the study if you currently have or have previously suffered from a problem with addiction to drugs or alcohol. You will not be able to take part in the study if you suffer from epilepsy. You will also not be able to take part in the study if you are on any regular medication (except the contraceptive pill, the Depo-Provera injection or the progesterone implant).
You will not be able to take part in the study if you are pregnant or if you are currently breast Due to the nature of MRI scanning, you will not be able to take part if there is any chance that there are metal objects or fragments inside your body, for example, if you have ever had metal implants as part of an operation. As the MRI scanner is a relatively small and partially enclosed space, it is also important that you do not participate if you suffer from claustrophobia. We will explain more about this at the screening visit. We are unable to include left handed volunteers as we are looking at brain activity and the location of this within the brain can differ with handedness.
Do I have to take part?
Taking part in the study is completely voluntary. We would ask you to sign a consent form to show
you have agreed to take part. If you do decide to take part in this study, you can withdraw at any
time without giving a reason.
What will happen to me if I take part?
This study will involve you taking either seven days (or eight days to allow for some flexibility of
meeting dates) treatment of either a drug, diazepam, or dummy capsules (placebo). Both the drug
and placebo will be in capsule form and you will need to take one capsule in the morning and two in
the evening every day for six or seven days, on the last day (day seven or eight) you will take only
your morning capsule. This study has a „double-blind‟ design meaning that neither you nor the
experimenter will know whether you are receiving the drug or the placebo. Although, if necessary
for any reason, it is possible for us to find out which treatment you have received. Half of the
volunteers in the study will receive the drug and the other half placebo.
If you decide to take part in the study then we will make an appointment for you to meet with us at
the Neurosciences Building at the Department of Psychiatry at a time that is convenient to you.
During this meeting, which would take about 60 minutes, we will give you a routine medical
examination (medical history, blood pressure check and weight measurement) and will ask you some
detailed questions about your mental health. We would also contact, with your permission, your GP
to check that there is no medical reason why you should not participate in the study.
If you are suitable and are willing to proceed, we would ask you to return to the Neurosciences
Building some days later, at this meeting we will issue you with a pack containing half the capsules
needed for the study for you to take home with you, along with instructions about when to take them.
You will be given detailed instructions about taking the capsules (this meeting will take around 30
mintues). We would also arrange to meet with you half way through the week to check how you are
getting on and to give you the remaining half of the capsules (this meeting will take around 30
minutes). On day six or seven (depending on whether you are taking seven or eight days of
treatment) we would ask you to take your morning dose at a certain specified time and to come for
testing either at the Neurosciences Building or the OCMR department of the John Radcliffe Hospital.
The subsequent day you would only take your morning dose, again at a certain specified time, and
would come for testing at a specified time in the location that you did not attend the previous day (ie
if you came to Neurosciences the previous day we would meet at OCMR on this day or vice versa).
Testing at the Neurosciences building will last for approximately 120-180 minutes and testing at
OCMR will last for approximately 120 minutes (with scanning for around 60-70 minutes within this).
See What will happen to me after taking the medication? for more details.
What is the drug that is being used?

The drug which we will use in this study is called diazepam. Diazepam is commonly used to treat
anxiety, agitation and panic attacks in the short term. The drug works by enhancing the effects of the
neurotransmitter (brain chemical) GABA. When it is used to treat anxiety diazepam is normally
given daily for 2-4 weeks at a dose of between 6 and 30 mg, and it is recommended that the daily
dose be divided into smaller doses throughout the day. In the present study we are giving 15 mg
daily divided into 5 mg morning and 10 mg evening doses. If you take part you will be randomly
allocated to receive either diazepam or placebo (dummy) capsules. In this study, the placebo that we
will use is lactose tablets.
When will I need to take this medication?

For the first six (or seven) days you will have to take your capsules twice a day once in the morning
after breakfast and once in the evening after your evening meal, on the last day (day seven or eight)
you will only need to take the morning dose. It is important that you take the capsules every morning
and evening, and that you take it at roughly the same time every day. Every day you will also be
required to fill out a short questionnaire, which we ask you to do immediately before taking the
capsule in the morning. Do not take more than specified number of capsules in any given day.
On the days when we meet for testing, you will be instructed to take your capsule at a certain
specified time.

What will happen to me after taking the medication?

We plan to study the effects of the medication on the brain by considering the ways in which it
affects performance on some simple psychological tasks. These will involve pushing keys in
response to words and pictures presented on the screen. In addition we would ask you to complete a
number of straightforward questionnaires. We are also interested in how diazepam might affect
decision-making about ethical issues and will ask to give your opinion about a few standard ethical
dilemmas (there are no right or wrong answers!). Some participants may find some components of
the ethical dilemma task either troubling or distasteful. If so, you may skip this story and move on to
the next.
During the fMRI scan, which will last about one hour, you will be required to complete some simple
tasks involving viewing and responding to pictures and words. There will also be a brief MRI scan
which allows us to get a picture of your brain.
What is MRI scanning?
MRI scanning works by using powerful magnetic fields to examine the tissues of the body. It is used
widely in medicine to provide images inside many different parts of the body to help doctors detect
diseases or to guide treatments. MRI is a routine procedure which is safe, painless and involves no
ionizing radiation. As well as an MRI scan to obtain an image of your brain for research purposes
only, we will be using a special method called functional MRI (fMRI) which is designed to measure
the activity levels in different parts of the brain. Having an MRI scan involves simply lying still
inside the scanner. During this time you will be made comfortable and you will be able to contact
researchers at all times. You will not feel anything, although you will hear some quite loud noises.
MRI and fMRI are both extremely safe procedures and thousands of people have such scans every
year. However, because of the magnetic fields involved, people who have fragments of metal or
shrapnel, other metallic objects, or medical implants in their bodies are generally not suitable for
MRI scanning (See Exclusion Criteria, below.)
The images of the brain which we will acquire are not suitable for medical purposes such as detecting
diseases. Although it is extremely unlikely, were we to see any structural abnormalities on your MRI
scan, a member of our research team would discuss the implications with you and, with your
permission, your GP might be notified. However, it is important to note that we do not carry out our
scans for diagnostic purposes, and our scans are not routinely assessed by an expert. Therefore, these
scans are not any kind of substitute for a clinical appointment.
When will the testing take place?
Testing will take place at the Department of Psychiatry and at the Oxford Magnetic Resonance
Research unit at the John Radcliffe Hospital on days six and seven or days seven and eight
(depending on scheduling) from the first day you took a capsule. Testing will take place at a
specified time.

What if I forget to take a dose?
If you forget to take one of the capsules, and you remember and are able to take it before lunchtime
in the case of the morning dose or before you go to bed in the case of the evening dose, please take
the capsule as soon as possible. No further action is required. If you do not remember in time, or are
unable to take it before lunchtime/before you go to bed, please contact us as soon as possible and we
will instruct you as to what to do. Please be aware that forgetting to take one capsule will not
generally mean that you will be excluded from the study, but it is very important for us to know.
Will I be able to drink alcohol while I am taking the medication?
It is very important that you do not drink alcohol whilst you are taking the medication, this is because
the sedative (sleep promoting) effects of alcohol will be increased by the drug.
Will I be able to smoke cigarettes while I am taking the medication?
We are able to include light smokers who smoke 5 or less cigarettes a day, and it is fine for you to
continue smoking at this level during participation in the study.
Will I be able to drive a car while I am taking the medication?
Diazepam can cause drowsiness, it is therefore important that you should not drive whilst taking it, as
your ability to do so safely may be impaired.
Will I be able to cycle my bike while I am taking the medication?
Diazepam can cause drowsiness, it is therefore important that you should not cycle whilst taking it,
as your ability to do so safely may be impaired.
Will I be able to operate machinery while I am taking the medication?
Diazepam can cause drowsiness, it is therefore important that you exercise caution whilst operating
machinery whilst taking it, especially if you are experiencing side effects which may affect your
ability to do so safely.
Risks and Benefits

Diazepam is generally well tolerated. Side effects that have been reported are drowsiness and
lightheadness the next day; confusion and ataxia (loss of coordination of movements); amnesia
(memory loss); dependence, which could lead to withdrawal being experienced; a paradoxical
increase in aggression and muscle weakness.
As noted above, there is a risk of developing dependency to diazepam. In healthy volunteers, at this
dosage and for this length of time we do not believe that the risk of developing dependency is high.
However, this risk is increased in individuals who have previously had drug or alcohol dependency
issues, so for this reason we are unable to include volunteers with a current or history of a drug or
alcohol dependency issue.
It is expected that volunteers who receive diazepam might experience some sedation for the first few
days in which they take the medication, we would anticipate that this would settle. Otherwise, we
believe that the chance of other side effects occurring is minimal. As we will meet part way through
the week this will give us the chance to assess how you are getting on. In addition, if you agree to
participate in the study, you will be given a list of contact details for researchers working on the
study, including a 24 hour contact that you can use in case you feel that you are experiencing any
negative side effects at any point. Given the potential for the drug to have sedative effects we do
NOT recommend that individuals who are undertaking academic or otherwise important work should
participate in this study, as the drug could impair concentration.
If you experience any negative side effects during the course of the study you should contact one of
the researchers on the study (you will be given a list of telephone contacts) or your GP immediately.
Sometimes clinical interviews and psychological questionnaires or tasks can ask for information that
might be potentially upsetting. However, all of these assessments are administered by trained staff
and questions can be asked at anytime. We will give you a debriefing session after the end of the
study and you are free to contact us with questions after the study if you wish. Some participants
may find some components of the ethical dilemma task either troubling or distasteful. If so, you may
skip this story and move on to the next.
By taking part in the study, you will have an opportunity to make a contribution to our scientific
understanding of how diazepam works and how the brain processes emotion.
Pregnancy (for women only)
Diazepam can be harmful to the foetus. Therefore, you must not take part in this study if you are
pregnant, if you suspect that you might be pregnant, or if you are trying to become pregnant.
Expenses and payments

If you take part in this study, you will be paid £100 for participation. We are also happy to reimburse
reasonable travel expenses. If you withdraw from the study prior to completion a prorata payment
will be made at the researchers discretion.
PART 2

What if there is a problem?
You will be given the phone number of one of the researchers for the duration of your involvement in
the study. You will be able to contact them if you have any concerns, both during the study and
afterwards. (See Risks and Benefits, above).
If you wish to complain about any aspect of the way in which you have been approached or treated
during the course of this study, you should contact Abbie Pringle, or you may contact the University
of Oxford Clinical Trials and Research Governance (CTRG) office on 01865 857939 or the head of
CTRG, email [email protected].
The University has arrangements in place to provide for harm arising from participation in the study
for which the University is the Research Sponsor.
Will my taking part in the study be kept confidential?

Yes. All the information about your participation in this study will be kept strictly confidential. Your
results will be coded with a participant number and no personal information will be attached to the
data. This anonymisation will occur at the point of data collection. Data will be stored on a
university computer for 10 years, while personal details will be stored separately in a locked filing
cabinet. Only the named researchers will have access to this data. The overall results of the study
may be published in scientific journals. However, all personal data will remain confidential, and no
data relating to individual participants will be published.
Responsible members of the University of Oxford may be given access to data for monitoring and/or
audit of the study to ensure that we comply with regulations.
What will happen if I don’t want to carry on with the study?
You can withdraw from this study at any time, without explanation. If you decide to withdraw, your
results will also be withdrawn.

Involvement of your General Practitioner (GP)

We will ask you to give us your permission to notify your GP that you are participating in the study.

What will happen to the results of the research study?

The results of this study may be published in a scientific journal. However, no information which
could be used to identify any individual participant will be published. If you are interested in finding
out about the results of this research, please let us know, and we will make arrangements to inform
you once the study is completed.
Who is organising and funding the research?

The study is sponsored by Oxford University and is funded by a grant from the Medical Research
Council (MRC), a national research funding board. The researchers are not being paid specifically
for including you in this study.

Who has reviewed the study?
All medical research conducted in the UK must be reviewed by a Research Ethics Council who
examine the ethical and scientific justifications for the study. This research has been reviewed by the
NRES Committee South Central – Southampton B (reference no 11/SC/0516)

Contact details
If you would like any further information on this study, or if you have any concerns, please contact
Abbie Pringle. Email: [email protected] or telephone: 01865 223956
Dr Abbie Pringle

FLOW CHART OF STUDY
First Appointment (60 mins)
Second Appointment (45 mins)
For next 7 or 8 days
Days 6 & 7 or Days 7 & 8
Day 4

Collect second half of capsules
Review

Source: http://www.ox.ac.uk/media/global/wwwoxacuk/localsites/studentgateway/documents/Information_sheet_Diazepam_Study.pdf