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RELIEVE IBS-D trial: Participant Information Sheet

 

Contents

This study is taking place at PRC:Newcastle, part of The Newcastle upon Tyne Hospitals NHS Foundation Trust. Please get in touch if you would like to take part.

Full Title: Randomised, double-blind, placebo controlled multi-centre study to assess the
efficacy, tolerability and safety of Enterosgel in the treatment of Irritable Bowel
Syndrome with diarrhoea (IBS-D) in adults

Short Title: Enterosgel® in the treatment of Irritable Bowel Syndrome with diarrhoea

Study Acronym: RELIEVE IBS-D

Study Code: ENT04UK

IRAS Project ID: 230930

Sponsor: Enteromed Ltd.

WHAT IS THE PURPOSE OF THE STUDY?

Many people suffer from Irritable Bowel Syndrome (IBS) every year in the UK. The causes of IBS are
complex and still not fully understood, but may include imbalances in the gut flora or immune function,
infections, dietary factors and changes to gut permeability (“leaky gut”). Depending on the stool
consistency, IBS can be classified as IBS with diarrhoea (IBS-D), IBS with constipation (IBS-C), or
mixed IBS (IBS-M).

The emergence of new drugs for IBS has been slow and there is a need for novel treatment alternatives,
including drug-free treatments, which are easy to use and can safely be used in different types of
patients, including in children and pregnant women. Currently available drug-free treatments include
Enterosgel®, which is an intestinal adsorbent that has been approved for use in patients with IBS-D
and has been available over-the-counter in the UK since 2014. It is an orally consumed gel-like product
classified as a medical device, which has been shown to adsorb harmful substances like bacterial toxins
in the gut. There have been studies suggesting that Enterosgel® and other intestinal adsorbents can
improve diarrhoea, bloating and abdominal pain in patients with IBS-D. However, the previous studies
have not been sufficiently large to accurately measure the benefits, and they have not included a
placebo control group. Larger studies where Enterosgel® is compared to a placebo, are needed to
further investigate the potential benefits of Enterosgel® in the treatment of IBS-D.

We are conducting this study to collect more scientific data about the potential benefits of using
Enterosgel® in the treatment of IBS-D. Although Enterosgel® is already available from pharmacies in
the UK, we will also collect data on its safety during this study as a standard research procedure. This
study is conducted by medical practices, hospital outpatient clinics and private clinics in the UK involving
430 adult patients. In the first part of the study, 215 participants will be randomly allocated to receive
Enterosgel® and 215 participants will be allocated to receive dummy treatment. Neither the participant
nor the research team will know which group the participant is allocated to. In the second part of the
study, all participants will receive Enterosgel®.

WHY HAVE I BEEN INVITED AND AM I ELIGIBLE?

You have received this information sheet because you have requested more information about the
study or because we have received your details through the ContactME-IBS register. A member of the
research team will confirm whether you are eligible.

You might be eligible to take part in the study if you:
• Are male or female aged 16-75
• Have Irritable Bowel Syndrome with diarrhoea (IBS-D) (a doctor will confirm this)
You are not eligible if you:
• Have a very mild or very severe form of IBS-D
• Have been diagnosed with gut abnormalities
• Have any other chronic intestinal disease
• Previously used Enterosgel®
• Are using antidepressant agents, unless you have used them at a stable dose for at least 6 weeks
• Are using slow-release medications or strong opioids
• Are using other intestinal adsorbents (activated charcoal, kaoline, diosmectite)
• Are currently participating, or have participated in the last three months, in research where
treatment is/was provided
• Are pregnant (women of childbearing potential should agree to use a medically accepted method
of contraception throughout the 2-week screening period and the 16 weeks when study treatment
is provided)

WHAT DOES TAKING PART IN THE STUDY INVOLVE?

Schedule and duration

The study will involve up to 6 remote appointments with the research team (please see contact details
at the end of this document). The appointments can be conducted either via a new secure video
consultation tool used by the NHS Trust, or by phone. The schedule of the appointments is:

Screening: up to 90min
Baseline (approximately 3 weeks from screening): up to 90min
Follow-up (2 weeks after Baseline): up to 15min
Follow-up (8 weeks after Baseline): up to 60min
Follow-up (16 weeks after Baseline): up to 60min
Follow-up (24 weeks after Baseline): up to 15min (NOTE: this is only required for patients who
responded to study treatment)


What happens during the study?

During the study, you will be asked to complete questionnaires asking about your IBS symptoms,
quality of life, work productivity, activity, and general health. The questionnaires will be posted to you
and should be completed either weekly or 4-weekly depending on the questionnaire. You will also
receive pre-paid envelopes to return the questionnaires to the research team.

In addition, you will be asked to keep a daily study diary to record IBS symptoms and treatment use.
This will only involve answering a few questions. The diary will be available as an online version which
can be accessed on mobile device or computer. The research team will explain how to use it. If you are
not able to use, or prefer not to use the electronic diary, you will receive a paper diary. The diary should
be completed daily for the first 18 weeks of the study.

Please note that you should not use any probiotic supplements, other intestinal adsorbents
(activated charcoal, kaoline, diosmectite), slow-release medications or strong opioids during
the study, or make any major changes to your diet. In addition, you should not use loperamide
during the 2-week screening period. Finally, please note that you should not take any medication
within 2 hours from taking the study treatment which you should take up to three times a day
depending on your symptoms. You can continue to take antidepressant agents at a stable dose
during the trial, provided that you have been taking a stable dose for at least 6 weeks.

Procedures conducted at each appointment are described below.

Screening appointment

The research team will first discuss the study with you and you will have an opportunity to ask questions
before you decide if you want to proceed. If you decide to take part in the study, you will be asked to
provide your written informed consent by electronically signing a consent form on an online system (the
research team will instruct you through this). In order to do this, you should have either a touch screen
smartphone or tablet or a computer/laptop. Your medical history will be reviewed by the research team.
If you meet the initial study eligibility criteria, you will be asked to record your symptoms in the study
diary over the next 2 weeks. If you use an electronic diary, then your data will be automatically reviewed
after 14 days. If the data suggests that you are not suitable to proceed, you will receive an automated
notification via email and text message to say you will not need to attend any further appointments. You
can always contact the research team if you have any questions.

If you do not meet the criteria to continue in the study at this stage, it may be possible to assess you
again at a later time. The research team will let you know if you might be suitable for this. It is important
that if you are interested to be assessed again in the future, you must not use any Enterosgel® as this
would make you ineligible for the study.

Baseline appointment

At the end of the 2-week assessment period, the research team will check your medical history and
current medications for any changes since Screening to determine whether you are eligible to take part
in the study. If you are a female of childbearing potential, you should also take a pregnancy test at home
on the morning of your appointment using a test kit posted to you. If you are confirmed to be eligible,
you will be randomly allocated to treatment group (Enterosgel® or placebo) and will be explained how
to use the study treatment for the next 8 weeks (see What treatment will I receive during the study?
below). Neither you nor the research team will know which treatment group you are allocated to.

Follow-up appointments

Two weeks after the Baseline appointment, the research team will give you a brief follow-up call to
check how you have been getting along with the treatment and the study diary.

At the week 8 and week 16 Follow-up appointments, the research team will ask about your medical
history and current medications for any changes since your last appointment, and will collect information
about any potential study treatment side effects. You will also be asked to complete questionnaires at
the end of every week and post these to the research team before the 8 week and 16 week appointment.
After the week 8 Follow-up, all participants will receive Enterosgel®. The research team will explain
how to take it for the next 8 weeks (see below).

If after 8 weeks (at week 16 Follow-up) you feel that the Enterosgel® treatment did not help to relieve

your symptoms, there will be no further follow-up from the research team and you will return to standard-
of-care. If you feel that the study treatment did help with your symptoms, the research team will give

you a brief follow-up phone call 8 weeks later to ask about your IBS and treatment use since stopping
the Enterosgel® treatment.

What treatment will I receive during the study?

If you are eligible to continue in the study after the 2-week assessment period, you will be randomly
allocated to a treatment group using a computer programme. Half of the participants will be assigned
to the Test Group and receive Enterosgel® for 8 weeks. Half of the participants will be assigned to the
Control Group and receive a placebo for 8 weeks. The treatment is blinded, which means that neither
the participants nor the research team will know which treatment group the participant was allocated to.
You will receive instructions on how to use the treatment and will have the treatment tubes delivered to
your home by a courier. You will be asked to provide consent to share your name, address and phone
number with the study Sponsor (Enteromed Ltd) and study supplies warehouse who will arrange a
courier delivery. They will aim to deliver the treatment to you within 1-2 days.

The study treatments will be provided in 90 ml tubes, each tube containing a single dose of Enterosgel®
or placebo. Both are liquids without any distinct flavour or smell. The products should be mixed with
approximately 100 ml of water and then consumed orally. You will receive up to 290 tubes for the 8-
week treatment period (up to 30 kg).

After the 8-week blinded treatment period, all participants will receive Enterosgel® for the following 8
weeks. You will have the treatment delivered to your home by a courier. The treatment will be provided
in the standard Enterosgel® sachets, which contain Enterosgel® in a gel-like formulation.

In addition, the research team will provide you with loperamide to use as needed during both 8-week
treatment periods.

If you start running out of treatment at any point of the study, please contact the research team who will
order additional supplies for you. After the 8-week Enterosgel® treatment period, you will no longer
receive any treatment as part of the study and will return to standard-of-care.

HOW CAN I TAKE PART?

If you are interested and wish to participate in the study, please contact the research team to schedule
an appointment (contact details provided at the end of this information sheet). Before enrolling you into
the study, they will go through your IBS-D symptoms and medical history to confirm whether you are
eligible to proceed to the 2-week assessment period. The research team will discuss the study with you
and you will have an opportunity to ask questions before you decide if you want to proceed. If you
decide to take part in the study, you will be asked to provide your signed informed consent and the

research team will then complete the first study appointment. After the 2-week assessment period, the

research team will confirm your eligibility to continue in the study.

In order for the research team to check your eligibility, you should ask your GP to provide you
with copies of your medical history summary and current medications list and post or email
these to the research team before or after your screening appointment. To ensure that your GP
provides the necessary information, we will provide you with a Medical Information Request
letter to give (or post or email) to your GP. You may also give your consent to our research team
to allow them to request the information from your GP on your behalf.

DO I HAVE TO TAKE PART?

No. It is up to you to decide if you want to take part in this study. If you decide not to take part, it will not
affect your medical care.

If you decide to take part, you will be free to withdraw from the study at any time without providing a
reason. This will not affect your medical care.

WHAT ARE THE POSSIBLE DISADVANTAGES OF TAKING PART AND SIDE EFFECTS
OF THE TREATMENT?

Enterosgel® is an intestinal adsorbent available over the counter in the UK. It is completely excreted
from the gut and does not get absorbed into the blood circulation. According to the manufacturer,
possible known side effects are nausea and constipation. If you experience any serious side effects
during the trial, please contact your local research team immediately at the number provided at the end
of this letter.

ARE THERE ANY BENEFITS FOR ME IN JOINING THE STUDY?

We cannot promise that the study will give you any direct benefit. However, your participation in the
study can help us collect important information in order to improve treatments for IBS-D.

IS THERE ANY REIMBURSEMENT FOR TAKING PART?

You will receive a £10 shopping voucher per appointment for Screening, Baseline and the two 60 min
Follow-up appointments as a reimbursement for inconvenience.
The research sites participating in this study will receive financial compensation for their time.

WHAT HAPPENS WHEN THE RESEARCH STUDY STOPS?

When the study has finished, your research team will be informed of the findings and will be encouraged
to share a summary on their website and/or newsletters. You will also find the results on the study
Sponsor’s website (http://enteromed.co.uk/relieve-ibs-d-trial/). In addition, the results will be reported in
medical journals. All results published will be anonymised, which means that you will not be identified
from them.

WHAT WILL HAPPEN IF I DON’T WANT TO CARRY ON WITH THE RESEARCH?

The study will be most valuable if few people withdraw from it, so it is important to discuss any concerns
you may have with a member of the research team before you agree to participate. However, you can
withdraw from the study at any time and without giving a reason. If you withdraw from the study, we will
stop collecting information from you. However, data collected before your withdrawal can be used for
the research.

WHO DO I CONTACT IF I HAVE ANY CONCERNS?

You can contact the research team at any time during the study should you have any concerns or
questions:

Tel: 0191 282 3655

Email: nuth.newcastlep3@nhs.net

If you have a complaint which cannot be resolved with the research team, for NHS research sites please
contact NHS England at: england.contactus@nhs.net or by telephone on 0300 311 22 33. You can
also send a letter by post to: NHS England, PO Box 16738, Redditch, B97 9PT.

If you are making a complaint please state: ‘For the attention of the complaints team’ in the subject line.
If you have a complaint about a non-NHS research site, please ask the site for information about their
complaint process.

The study Sponsor, Enteromed Ltd, has arrangements in place to provide compensation for harm
arising from participation in any trial for which they are the Sponsor. NHS indemnity operates in respect
of the clinical treatment with which you are provided. Private clinics participating in this study are
required to have clinical trials insurance.

For general information about clinical trials, the UK Clinical Research collaboration (UKCRC) publishes
a leaflet entitled "understanding clinical trials". This leaflet gives you information about medical research
and looks at some questions you may want to ask. The leaflet is available online at:
http://www.ukcrc.org/wp-content/uploads/2014/03/iCT_Booklet.pdf

HOW WILL INFORMATION ABOUT ME BE KEPT CONFIDENTIAL?

Enteromed Ltd is the sponsor for this study based in the United Kingdom. They will be using information
from you and/or your medical records in order to undertake this study and will act as the data controller
for this study. This means that Enteromed Ltd are responsible for looking after your information and
using it properly. Enteromed Ltd will not keep any identifiable information about you after the study has
finished.

Your rights to access, change or move your information are limited, as we need to manage your
information in specific ways in order for the research to be reliable and accurate. If you withdraw from
the study, the research team and the sponsor will keep the information about you that we have already
obtained. To safeguard your rights, we will use the minimum personally-identifiable information
possible. You can find out more about how Enteromed Ltd use your information by contacting
IBS@enteromed.co.uk.

The research site/clinic will collect information from you and/or your medical records for this research
study in accordance with our instructions. We will use your name and contact details to contact you
about the research study, and make sure that relevant information about the study is recorded for your
care, and to oversee the quality of the study. Individuals from Enteromed Ltd and regulatory
organisations may look at your medical and research records to check the accuracy of the research
study. The research site/clinic will pass these details to Enteromed Ltd along with the information
collected from you and/or your medical records. The only people in Enteromed Ltd, or third parties
contracted by Enteromed Ltd, who will have access to information that identifies you will be people who
need to arrange or contact you regarding study treatment deliveries or audit the data collection process.
The people who analyse the information will not be able to identify you and will not be able to find out
your name, NHS number or contact details.

The research site/clinic will keep identifiable information about you from this study for 5 years after the
study has finished.

When you agree to take part in a research study, the information about your health and care may be
provided to researchers running other research studies in this organisation and in other organisations.
These organisations may be universities, NHS organisations or companies involved in health and care
research in this country or abroad. Your information will only be used by organisations and researchers
to conduct research in accordance with the UK Policy Framework for Health and Social Care Research.
This information will not identify you and will not be combined with other information in a way that could
identify you. The information will only be used for the purpose of health and care research, and cannot
be used to contact you or to affect your care. It will not be used to make decisions about future services
available to you, such as insurance.

If you are enrolled into the study at a clinic or a different medical practice than where you are registered,
your GP will be informed of your participation in the study. Your GP will be allowed to share your relevant
medical history and list of medications with the research team conducting the research.

WHO IS ORGANISING AND FUNDING THE STUDY?

The study is organised by Enteromed Limited, who are the distributor of Enterosgel® in the UK. The
study is funded by Bioline Products s.r.o (Czech Republic) and supported by the NHS National Institute
for Health Research (NIHR).

WHO HAS APPROVED THE STUDY?

All research in the NHS is reviewed by an independent group of people, called a Research Ethics
Committee, which is there to protect your safety, rights, wellbeing and dignity. This study has been
reviewed and was given a favourable review by the North East – Tyne & Wear South Research Ethics
Committee.

SOURCE FOR MORE INFORMATION:

Information about Enterosgel® can be found at: www.enterosgel.co.uk.

If you have any questions or queries or require any advice about any aspect of this study, please contact
the research team whose details are provided below.

Professor Yan Yiannakou
Hazel Forsyth – Senior Research Sister
The NIHR National Patient Recruitment Centre, Newcastle
Campus for Ageing and Vitality
Westgate Road
Newcastle upon Tyne
NE4 6BE
Tel: 0191 282 3655

Thank you for taking time to read this Information Sheet.