RELIEVE IBS-D trial: Participant Information Sheet
This study is took place atPRC:Newcastle, part of The Newcastle upon Tyne Hospitals NHS Foundation Trust.
In the first part of the study, eligible participants will be randomly allocated to receive either Enterosgel® or placebo for an 8 week period. Neither the participant nor the research team will know which group the participant is allocated to. For the second part of the study, all participants will receive Enterosgel® for 8 weeks.
Over the course of the study up to 6 remote appointments will take place with the research team. These appointments can be conducted either via a new secure video consultation tool used by the NHS Trust, or by phone. At appointments medical history will be reviewed to check eligibility and to monitor symptoms and adverse effects. Throughout the study, participants will be asked to complete brief weekly paper questionnaires exploring the impact ofIBS on their daily lives. In addition, they will be asked to keep a short daily study diary to recordIBS symptoms and treatment use. This is available as an online version which can be accessed on mobile device or computer and takes less than 90 seconds to complete.
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
Enterosgel® in the treatment of Irritable Bowel Syndrome with diarrhoea
IRAS Project ID
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
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.
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.
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.
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 30kg).
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. 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
If you have a complaint which cannot be resolved with the research team, for NHS research sites please contact NHS England at: firstname.lastname@example.org 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 here.
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 here.
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
Newcastle upon Tyne
Tel: 0191 282 3655
Thank you for taking time to read this Information Sheet.