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information sheet v1.6 _08-08_-1


									                           Patient information sheet

Project title: Lactamica 2- Discovering new methods of inhibiting
carriage of Neisseria meningitidis
Protocol number v1.6 Aug 2011
We would like to invite you to take part in our research study. Before you decide we
would like you to read this information sheet to understand why the research is being
done and what it would involve for you. One of our study team will go through the
information sheet with you and answer any questions you have. Talk to others about
the study if you so wish.
We are a research team based in the Medical School at Sheffield University who
study a bacteria called Neisseria meningitidis which causes meningitis and other
serious illnesses, but also lives harmlessly in the nose and throat of many young
adults. Our work focuses on preventing disease caused by this bacteria.
Part 1 of this information sheet will explain the purpose of this study and what will
happen if you take part, and part 2 gives more detail about the conduct of the study.

Part 1
What is the purpose of this study?
Neisseria meningitidis is a bacteria which can cause serious disease. However, it
also lives harmlessly in the nose and throat of many young adults (a process called
colonisation). Currently, there are vaccines against several strains of this bacteria
which help prevent disease, but not all of them. We are investigating the relationship
between this bacteria and a related bacteria Neisseria lactamica in order to provide
information about proteins that could help in future vaccines and to explore other
strategies which might prevent the growth of the harmful bacteria in humans. A
previous research project we carried out suggested that the introduction of this
related, but harmless bacteria, Neisseria lactamica into the noses of healthy
individuals prevented people becoming infected with Neisseria meningitidis. In
addition it suggested there are people who are resistant to colonisation with this type
of bacteria. We would like to study this effect further with a larger group of people to
look at what happens to colonisation with Neisseria meningitidis when people are
colonised with Neisseria lactamica. Specifically we wish to see whether inoculation
of Neisseria lactamica will stop colonisation by Neisseria meningitidis and whether
some people are definitely resistant to it. If we find a positive effect we will seek to
discover the mechanism by examining samples from the noses of volunteers
including DNA from you the volunteer, and the bacteria that you carry.
In summary we would like to administer nose drops containing live Neisseria
lactamica bacteria into your nose and then take successive throat swabs to identify
the effect on colonisation with Neisseria meningitidis.

                                                          Information Sheet/ STH16097/v1.6 (Aug 2011)
Do I have to take part?
No - participation is completely voluntary.

What will be involved if I want to take part?
First of all we will ask you some questions to check your general health, and ensure
you do not have health conditions that could put you at risk if you take part in this
study. In addition we will ask some further information that might influence the kind of
bacteria that you have in the back of your throat, such as exposure to cigarette
smoke and how many people live in your household.
On your second visit we will ask you to provide a saliva sample – from this we will
extract your DNA and store it for later analysis (see below). Then we will take 3
swabs from the back of your throat, one will be cultured to see if you carry
Neisseria.meningitidis, the second we will store for later bacterial DNA extraction and
identification of all of the organisms that live at the back of your throat, and the third
we will use for extraction of bacterial RNA (Ribonucleic Acid- a substance similar to
After this we will randomly allocate you to receive either drops containing live
bacteria, or a water like solution into the back of your nose. The nose drops will
contain a carefully measured number of bacteria of Neisseria lactamica. The
preparations of bacteria will be made by the Department of Health's laboratories at
Porton Down and will be prepared for final instillation in the sterile facilities here at
the University of Sheffield. Following this procedure we will ask you to come back at
2, 4, 8, 16 and 24 weeks to have your throat re-swabbed and other samples taken.
At each visit we will ask you if you have been unwell since your last visit and if you
have taken or are taking any oral antibiotics.
Throat swabs for bacterial culture will be taken at all visits, in addition at visits 3, 4
and 7 additional samples will be taken. At visit 3 a throat swab will be taken for
extraction of bacterial RNA. At visit 4 a throat swab will be taken for the extraction of
bacterial DNA and a sample of nasal fluid secretion will be collected. This involves
placing a small piece of filter paper inside one of your nostrils and collecting fluid. At
visit 7 three throat swabs will be taken for culture of bacteria, for collection of
bacterial RNA and collection of bacterial DNA.
At visit 7 we will also repeat the administration of bacteria containing drops for all
participants. The final visit will be in week 26 when we will perform three throat
swabs, collect and collect some skin cells using a brushing technique from your nose
from which we will later extract RNA to identify proteins that help in colonisation.

What will happen to me if I take part?
You will have a number of throat swabs. This test involves brushing a cotton wool
swab (on a stick) against the back of your mouth between the tonsils. Sometimes
this can lead to a strange sensation called gagging which lasts no more than a
couple of seconds.
You will also provide a saliva sample. In this test we will ask you to spit into a pot.

                                                            Information Sheet/ STH16097/v1.6 (Aug 2011)
In addition you will have one nasal brush sample taken. This involves us inserting a
small brush (on a stick) into one nostril and rotating it to collect some of your nasal
skin cells. This can leave you with watery eyes and can be uncomfortable for a few
The final sample is a sample of nasal secretions. This is collected using a small
piece of filter paper. The filter paper is placed on the inside of your nostril and left for
5 minutes. After this time it will have collected a small amount of fluid which we will
take to the laboratory.
We will provide you with a table showing precisely when the procedures will be done
at each visit.

What are the possible disadvantages and risks of taking part in this study?
Neisseria lactamica is a harmless bacteria which lives in the nose and throat of
young children. It has only rarely been documented to have caused disease, and in
people with a low level of immunity.

Has this ever been done before?
Yes, we have previously carried out a similar study in which a total of 41 individuals
received live challenge. 24 of these individuals received a further re-challenge with
the bacteria. No adverse events or symptoms were reported. The model for safe
inoculation has been standardized and is safely reproducible.

Are there any risks to others?
Once people are colonised with the N.lactamica bacteria there is a theoretical risk
that the bacteria can be passed on to other people you have close contact with. The
risk of this can be reduced by good hygiene, washing your hands after you have
touched your face, particularly after coughing, sneezing or scratching. The
consequences of close contacts becoming colonised with N.lactamica are the same
as for you- it is a normal coloniser of the human throat is thought to be harmless.
Nonetheless, if you regularly share a bedroom with another person we would advise
you to inform them that you are taking part in this study. Furthermore, you should
not participate if any household contacts are immunosuppressed. If you are not
certain about this please discuss it with the research doctor.

Will my taking part in the study be kept confidential?
Yes. We will follow ethical and legal practice and all information about you will be
handled in confidence. The details are included in part 2. At the screening visit some
basic information will be collected from you. All of this information will be kept

Will my GP be informed of my participating in this study?
Yes he will be informed that you are involved in the study and he will be given an
explanation of the research project.

                                                             Information Sheet/ STH16097/v1.6 (Aug 2011)
Will you be keeping any tissue that belongs to me?
Yes, during this project we will collect a saliva sample and a swab sample from
which we will later extract genetic material –DNA and RNA from the cells that line
your nose and throat. We will store this material for 7 years after we have
anonymised it, so that it cannot be linked with your name. If we discover that
Neisseria lactamica does stop Neisseria meningitidis colonisation, and if we discover
that there is a fixed population who cannot be colonised by one or either of these
bacteria, we will seek to discover the reason for this. To do this we will use your RNA
(collected in the nasal brushings) and the nasal secretions (collected using the filter
paper) to discover proteins that are made in the nose and which differ between those
who are, and those who are not colonised. If we identify relevant proteins, we will
then use your DNA to see if there is a difference in genes that explains this.
You will need to give your consent explicitly for storage of your DNA/RNA for future
use. If you do not wish to give your consent for the collection of these samples it is
still possible to take part in the study.
In addition we will store the bacteria collected from your nose indefinitely and
examine its DNA.

Will the information used in the study be confidential?
Anything you say will be treated in confidence, no names will be mentioned in any reports
of the study, and care will be taken so that individuals cannot be identified from details in
reports of the results of the study. In screening you for participation in the study we will
ask certain questions such as do you have any medical conditions or take any medicines.
The answers to these questions will be kept confidential and if they are deemed to result
in your exclusion from participating the results will not be kept.

Will I benefit from the study?
No. It is unlikely that you will benefit directly from this study. We hope that the
information gained from the study will help inform the development of strategies to
prevent people acquiring meningitis and meningococcal septicaemia in the future.

We appreciate that there will be a certain amount of inconvenience as a result of
taking part in this study and so will be offering £120 pounds to each volunteer as
compensation. This will be given in two separate amounts of £60 at weeks 16 and 26
of the study.

Part 2
What will happen if I don’t want to carry on with the study?
If you wish to withdraw from the study you are free to do so at any time. In such an
event we would continue to use any data we collected up to the point of your
withdrawal. With your permission we would continue to store any samples already
collected for later DNA/RNA extraction, but would destroy these samples if you so

                                                          Information Sheet/ STH16097/v1.6 (Aug 2011)
What should I do if there is a problem?
If you were to fall ill during the study and require medical help we would advise you
to first seek the advice of your GP. We will provide you with a letter explaining the
study to your GP which will contain contact number for the research team and the
Infectious Disease unit at the Royal Hallamshire Hospital. The GP would be
encouraged make contact if there were any concerns about your health during the

What if I wish to complain about the way the study was conducted?
If you have cause to complain about any aspect of the way in which you have been
approached or treated during the course of this study, the normal National Health
Service complaints mechanisms are available to you and you are not compromised
in any way because you have taken part in a research study.
The research lead is Professor Robert C. Read in Sheffield. If you wish to discuss
the study further please contact Professor Read, either by asking the Clinical
Research Fellow, Dr Alice Deasy or any of the research team who approached you,
or by telephoning him directly on 0114 2713843. Otherwise you can complain
directly to the Medical Director who manages Professor Read: Dr Mike Richmond,
Medical Directorate, 8 Beech Hill Road, Sheffield S10 2SB, Tel: 0114 2712178.

Will any genetic test be done?
During this study we will collect throat swabs, saliva and nasal brush samples from
which we will collect genetic material from both the bacteria and from your nasal skin
cells. Using these samples we will later collect DNA from the bacteria present in the
throat, and DNA and a similar genetic material RNA from your nasal skin cells. We
will use the DNA from your skin cells to study any genetic differences that exist
between those people who were colonised with the N.lactamica bacteria and those
that were not. In addition using the RNA material we will study the proteins that are
expressed in those people colonised with the bacteria compared to those that were

What happens when the research study stops?
We will use the results of the research to explore new ways of preventing meningitis.

What will happen to the results of the research study?
The results from this research study will be published in a peer reviewed journal.

Who is organising and funding the research?
The research is being organised and funded by Meningitis UK, and is being
sponsored by Sheffield Teaching Hospitals NHS Foundation trust. There are no
conflicts of interest for any of the research team working on this study.

Who has reviewed the study?
All research in the NHS is reviewed by an independent Research Ethics Committee
to protect your interests. The study has been reviewed and approved by Meningitis
UK and the Bradford Research Ethics Committee.

                                                         Information Sheet/ STH16097/v1.6 (Aug 2011)
Who can I speak to if I have any questions about this research study?
If you have any questions regarding this research study please contact Dr Alice

                                                    Information Sheet/ STH16097/v1.6 (Aug 2011)

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