Enterosgel® in the treatment of Irritable Bowel Syndrome with Diarrhoea
| ISRCTN | ISRCTN17149988 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN17149988 |
| Secondary identifying numbers | ENT04UK |
- Submission date
- 14/11/2017
- Registration date
- 15/11/2017
- Last edited
- 20/09/2022
- Recruitment status
- No longer recruiting
- Overall study status
- Completed
- Condition category
- Digestive System
Plain English Summary
Background and study aims
Irritable Bowel Syndrome (IBS) is a common condition with symptoms causing around 1 in 10 people to seek help from their GP at some point in their lives. It is a combination of abdominal discomfort or pain and altered bowel habits. 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). IBS is often a chronic condition that can significantly impair quality of life and cause absence from work and school. The emergence of new drugs for IBS has been slow and there is a need for new 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 is available over-the-counter in the UK. 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, larger studies are needed to further investigate the potential benefits of Enterosgel® in the treatment of IBS-D. This study aims to recruit 430 participants with IBS-D. The goal is to investigate whether Enterosgel® can improve IBS-D symptoms, including diarrhoea and abdominal pain. In addition, the study aims to investigate the impact of this treatment on the quality of life, work productivity and activity and general health. The safety and tolerability of Enterosgel® in this condition will also be evaluated.
Who can participate?
Adults aged 16-75 who have been diagnosed with IBS-D and have diarrhoea symptoms
What does the study involve?
The study involves in total four visits and one follow-up call over 26 weeks. At each visit and at given time points between the visits, the participants complete questionnaires asking about their IBS symptoms, quality of life, work productivity and activity and general health. In addition, the participants are asked to complete a study diary throughout the study to record their symptoms and treatment use. The diary is available as an electronic and paper diary. The diary should be completed daily for the first 18 weeks. At the first visit (week 0), potential participants are provided with the study diary to record their diarrhoea and abdominal symptoms for 2 weeks. Those who had sufficientsymptoms over this period are eligible to take part in the study and are randomly allocated to one of two treatment groups at the second visit (week 2). The first group receive dummy treatment and the second group receive Enterosgel® for 8 weeks. Neither the participants nor the research team know which treatment the participant receives. After 8 weeks, the participants attend the third visit (week 10) and all participants are given Enterosgel® for the next 8 weeks. This time, the participants are informed about the treatment they receive. After 8 weeks of treatment with Enterosgel®, the participants attend the fourth study visit (week 18) and return to standard-of-care. A final follow-up call takes place 8 weeks later (week 26).
What are the possible benefits and risks of participating?
To allow all patients to try Enterosgel®, this study includes an 8-week period where all participants receive it. Some participants may find that Enterosgel® helps with their IBS symptoms while others might not experience any benefit. The aim of this study is to evaluate what proportion of participants can benefit from this treatment, and what the benefits are. In the future, this information can be helpful to the patients and healthcare professionals when they are considering different treatment alternatives. Enterosgel® has been available in some countries for 30 years and is commonly used as a treatment for gastrointestinal conditions, including acute diarrhoea and IBS-D. According to the manufacturer, possible known side effects are nausea and constipation. Enterosgel® is completely excreted from the gut and does not get absorbed into the blood circulation.
Where is the study run from?
This study will be conducted at about 30 medical practices, secondary care centres and private clinics in the UK and a virtual site. In addition to the participating research sites, the study is advertised through local pharmacies and through an IBS research register called ContactME-IBS (https://www.contactme-ibs.co.uk)
When is the study starting and how long is it expected to run for?
March 2017 to October 2021
Who is funding the study?
Bioline Products s.r.o
Who is the main contact?
Dr Carol Howell
Contact information
Scientific
Enteromed Ltd
85 Great Portland Street
London
W1W 7LT
United Kingdom
| Phone | +44 (0)7596887046 |
|---|---|
| research@enteromed.co.uk |
Study information
| Study design | Randomised double-blind placebo-controlled multi-centre trial |
|---|---|
| Primary study design | Interventional |
| Secondary study design | Randomised controlled trial |
| Study setting(s) | Hospital |
| Study type | Treatment |
| Participant information sheet | Not available in web format, please use the contact details below to request a patient information sheet |
| Scientific 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 (RELIEVE IBS-D) |
| Study acronym | RELIEVE IBS-D |
| Study hypothesis | The hypothesis is that Enterosgel® is superior compared with placebo in terms of patient-reported outcomes for stool consistency and abdominal pain, in patients with IBS-D. |
| Ethics approval(s) | North East - Tyne & Wear South Research Ethics Committee, 19/02/2018, REC ref: 18/NE/0023 |
| Condition | Irritable Bowel Syndrome with diarrhoea (IBS-D) |
| Intervention | Using a centralised computer-based randomisation tool, patients will be randomised 1:1 to receive intestinal adsorbent Enterosgel® or placebo. The patients will receive blinded study treatment for 8 weeks according to study-specific dosage instructions, which allow adjusting the dosage based on IBS symptoms. The treatment is provided in 90g tubes, each containing a single treatment dose. The Enterosgel® tubes contain 22.5g Enterosgel® pre-diluted in water. The placebo tubes contain water with chalk added to mimic the appearance and consistency of Enterosgel®. Updated 17/10/2018: The control group will receive identical tubes containing placebo. Treatments are taken orally up to 6 doses per day, depending on the symptoms. After 8 weeks of blinded treatment, all patients will receive open-label Enterosgel® treatment for 8 weeks to take if they experience diarrhoea. Following the open-label treatment period, all patients will return to standard-of-care and will be followed up for 8 weeks. |
| Intervention type | Device |
| Pharmaceutical study type(s) | |
| Phase | Not Applicable |
| Drug / device / biological / vaccine name(s) | |
| Primary outcome measure | Percentage of patients defined as responders for abdominal pain and stool consistency based on daily study diary data, during at least 4 weeks in the 8-week blinded treatment period, where: 1. An Abdominal Pain Intensity Weekly Responder is defined as a patient who experiences a decrease in the weekly average abdominal pain score of at least 30 percent compared with baseline. The weekly average abdominal pain score is derived by scoring the worst pain experienced each day and taking the average for one week AND 2. A Stool Consistency Weekly Responder is defined as a patient who experiences a 50 percent or greater reduction in the number of days per week with at least one stool that has a consistency of Bristol Stool Form Scale (BSFS) Type 6 or 7 compared with baseline |
| Secondary outcome measures | Original secondary outcome measures: Double-blind treatment phase and open-label treatment phase: 1. Stool frequency based on daily study diary data; mean over 8 weeks and the last 4 weeks of each treatment period 2. Stool consistency assessed as average number of days/week with Bristol Stool Scale type >5 based on daily study diary data and percentage of responders over 8 weeks and the last 4 weeks of each treatment period 3. Abdominal pain based on daily study diary data; mean on a VAS scale from 0 to 10 over 8 weeks and the last 4 weeks, percentage of responders over 8 weeks and the last 4 weeks of each treatment period 4. Bloating based on weekly study diary data; mean weekly score on a numerical scale from 0 to 6 over 8 weeks and the last 4 weeks of each treatment period 5. Urgency based on weekly study diary data; mean weekly score on a numerical scale from 0 to 6 over 8 weeks and the last 4 weeks of each treatment period 6. Percentage of patients reporting adequate relief of global IBS symptoms based on weekly study diary data weekly from baseline until week 8 of each treatment period 7. Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) score weekly from baseline until week 8 of each treatment period 8. Irritable Bowel Syndrome Quality of Life (IBS-QOL) score every 4 weeks from baseline until week 8 of each treatment period 9. Patient Health Questionnaire-12 Somatic Symptom scale (PHQ-12 SS) score to measure severity of somatic symptoms excluding gastrointestinal symptoms every 4 weeks from baseline until week 8 of each treatment period 10. IBS-related Work Productivity and Activity Impairment (WPAI:IBS) score; weekly from baseline until week 8 of each treatment period 11. Use of rescue medication, i.e. loperamide, based on weekly study diary data; number of days over each 8 weeks of treatment 12. Adverse events over each 8 weeks of treatment Follow-up: 1. Satisfaction with bowel symptoms based on weekly study diary data; mean weekly score on a numerical scale from 0 to 6, over 8 weeks 2. Satisfaction with abdominal pain based on weekly study diary data; mean weekly score on a numerical scale from 0 to 6, over 8 weeks 3. Loperamide use based on weekly study diary data; mean number of days per week over 8 weeks 4. Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) score at baseline and 8 weeks 5. Patient Health Questionnaire-12 Somatic Symptom scale (PHQ-12 SS) score to measure severity of somatic symptoms excluding gastrointestinal symptoms at baseline and 8 weeks 6. Irritable Bowel Syndrome Quality of Life (IBS-QOL) score at baseline and 8 weeks 7. IBS-related Work Productivity and Activity Impairment (WPAI:IBS) score at baseline and 8 weeks 8. Percentage of patients who maintained treatment benefit over 8 weeks after cessation of treatment based on weekly study diary data over 8 weeks Updated 17/10/2018: Follow-up: In patients who reported adequate relief in the last 4 weeks of open-label period: 1. Maintenance of treatment benefit (percentage of patients who report increased or maintained treatment benefit at 8 weeks) 2. Enterosgel® use (percentage of patients who report having used Enterosgel® during the follow-up period; frequency of use in these patients) 3. Loperamide use (percentage of patients who report having used less loperamide during the follow-up period than before the trial) 4. Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) score at baseline and 8 weeks 5. Patient Health Questionnaire-12 Somatic Symptom scale (PHQ-12 SS) score to measure severity of somatic symptoms excluding gastrointestinal symptoms at baseline and 8 weeks 6. Irritable Bowel Syndrome Quality of Life (IBS-QOL) score at baseline and 8 weeks 7. IBS-related Work Productivity and Activity Impairment (WPAI:IBS) score at baseline and 8 weeks 8. Percentage of patients who maintained treatment benefit over 8 weeks after cessation of treatment based on weekly study diary data over 8 weeks Updated 07/01/2020: Double-blind treatment phase and open-label treatment phase: 1. Stool frequency based on daily study diary data; mean over 8 weeks and the first and last 4 weeks of each treatment period 2. Stool consistency assessed as average number of days/week with Bristol Stool Scale type >5 based on daily study diary data (over 8 weeks and the first and last 4 weeks of each treatment period) and percentage of responders 3. Abdominal pain based on daily study diary data; mean on a VAS scale from 0 to 10 over 8 weeks and the last 4 weeks, percentage of responders over 8 weeks and the last 4 weeks of each treatment period 4. Bloating based on weekly study diary data; mean weekly score on a numerical scale from 0 to 6 over 8 weeks and the last 4 weeks of each treatment period 5. Urgency based on weekly study diary data; mean weekly score on a numerical scale from 0 to 6 over 8 weeks and the last 4 weeks of each treatment period 6. Percentage of patients reporting adequate relief of global IBS symptoms based on weekly study diary data over 8 weeks and the first and last 4 weeks of each treatment period 7. Irritable Bowel Syndrome Severity Scoring System (IBS-SSS) score average over 8 weeks and the first and last 4 weeks 8. Irritable Bowel Syndrome Quality of Life (IBS-QOL) 4-weekly score average over 8 weeks and week 4 and week 8 scores 9. Patient Health Questionnaire-12 Somatic Symptom scale (PHQ-12 SS) score to measure severity of somatic symptoms excluding gastrointestinal symptoms 4-weekly score average over 8 weeks and week 4 and week 8 scores 10. IBS-related Work Productivity and Activity Impairment (WPAI:IBS) weekly score average over 8 weeks of each treatment period 11. Use of rescue medication, i.e. loperamide, based on weekly study diary data; number of days over 8 weeks and the last 4 weeks 12. Adverse events over each 8 weeks of treatment |
| Overall study start date | 01/03/2017 |
| Overall study end date | 31/10/2021 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Mixed |
| Lower age limit | 16 Years |
| Upper age limit | 75 Years |
| Sex | Both |
| Target number of participants | 430 |
| Total final enrolment | 439 |
| Participant inclusion criteria | Current inclusion criteria as of 04/04/2019: 1. Written informed consent 2. Irritable Bowel Syndrome with diarrhoea (IBS-D) according to Rome IV criteria 3. Aged 16-75 4. Considered suitable to take part in the study by the consenting doctor/nurse 5. Diary completed on at least 11 of 14 days (≥75%) during the screening period Previous inclusion criteria from 17/10/2018 to 04/04/2019: 1. Written informed consent 2. Irritable Bowel Syndrome with diarrhoea (IBS-D) according to Rome IV criteria 3. Aged 18-75 4. Considered suitable to take part in the study by the consenting doctor/nurse 5. Diary completed on at least 11 of 14 days (≥75%) during the screening period Original inclusion criteria: 1. Irritable Bowel Syndrome with diarrhoea (IBS-D) according to Rome IV criteria 2. Negative calprotectin test or adequate exclusion of Inflammatory Bowel Disease (IBD) 3. Aged 18+ 4. Considered suitable to take part in the study by the consenting physician |
| Participant exclusion criteria | Current exclusion criteria as of 07/01/2020: 1. Loose stools (BSFS 6 or 7) on less than 3 days during the 14 days after Screening Visit 2. Average abdominal pain <2.5 during the 14 days after Screening Visit (scale 0–10: 0 = no pain; 10 = worst possible pain) 3. Previously diagnosed coeliac disease 4. Previously diagnosed Inflammatory Bowel Disease 5. Previous bowel cancer or bowel resection 6. Other previously known gastrointestinal disorder contributing to the diarrhoea 7. Unexplained weight loss 8. Unexplained rectal bleeding 9. Previous use of Enterosgel® 10. Use of antidepressant agents, unless used at a stable dose for at least 6 weeks 11. Use of any probiotic supplements, other intestinal adsorbents, slow-release medications or strong opioids 12. Participation in any research where treatment is provided, or was provided in the last three months 13. Pregnancy Previous exclusion criteria from 04/04/2019 to 07/01/2020: 1. Loose stools (BSFS 6 or 7) on less than 3 days during the 14 days after Screening Visit 2. Average abdominal pain <3 during the 14 days after Screening Visit (scale 0–10: 0 = no pain; 10 = worst possible pain) 3. Previously diagnosed coeliac disease 4. Previously diagnosed Inflammatory Bowel Disease 5. Previous bowel cancer or bowel resection 6. Other previously known gastrointestinal disorder contributing to the diarrhoea 7. Unexplained weight loss 8. Unexplained rectal bleeding 9. Previous use of Enterosgel® 10. Use of antidepressant agents, unless used at a stable dose for at least 6 weeks 11. Use of any probiotic supplements, other intestinal adsorbents, slow-release medications or strong opioids 12. Participation in any research where treatment is provided, or was provided in the last three months 13. Pregnancy Previous exclusion criteria from 17/10/2018 to 04/04/2019: 1. Loose stools (BSFS 6 or 7) on less than 3 days during the 14 days after Screening Visit 2. Average abdominal pain <3 during the 14 days after Screening Visit (scale 0–10: 0 = no pain; 10 = worst possible pain) 3. IBS-SSS≥400 4. Previously diagnosed coeliac disease 5. Previously diagnosed Inflammatory Bowel Disease 6. Previous bowel cancer or bowel resection 7. Other previously known gastrointestinal disorder contributing to the diarrhoea 8. Unexplained weight loss 9. Unexplained rectal bleeding 10. Previous use of Enterosgel® 11. Use of antidepressant agents, unless used at a stable dose for at least 6 weeks 12. Use of any probiotic supplements, other intestinal adsorbents, slow-release medications or strong opioids 13. Participation in any research where treatment is provided, or was provided in the last three months 14. Pregnancy Original exclusion criteria: 1. Loose stools (BSFS 6 or 7) on less than 3 days during the last 14 days before Baseline 2. IBS-SSS≥400 3. Organic gastrointestinal disorder 4. Celiac disease (existing diagnosis) 5. Lactose malabsorption (existing diagnosis) 6. Bile acid malabsorption (existing diagnosis) 7. Bowel cancer 8. Previous use of Enterosgel® 9. Pregnancy 10. Diary completed on at least 11 of 14 days (≥75%) during the screening period |
| Recruitment start date | 15/10/2018 |
| Recruitment end date | 21/04/2021 |
Locations
Countries of recruitment
- England
- United Kingdom
Study participating centres
United Kingdom
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Doncaster
DN2 5LT
United Kingdom
Manchester
M23 9LT
United Kingdom
Sponsor information
Industry
85 Great Portland Street
London
W1W 7LT
United Kingdom
| Website | http://enteromed.co.uk |
|---|---|
"ROR" |
https://ror.org/013bz8f47 |
Funders
Funder type
Industry
No information available
Results and Publications
| Intention to publish date | 31/03/2022 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Available on request |
| Publication and dissemination plan | Current publication and dissemination plan as of 15/09/2022: Study results were submitted for presentation(s) at the British Society for Gastroenterology Conference (June 2022) and published in the scientific journal GUT online on 27/06/2022 (doi: 10.1136/gutjnl-2022-327293). Results were disseminated to patients at an interactive webinar which is now available on the study website for patients and the public to view. The protocol will be made available immediately following publication with no end date. Previous publication and dissemination plan: Study results will be submitted for presentation(s) at gastroenterology conference(s) and for publication in international peer-reviewed scientific journal(s). Results will be disseminated to the patients and the public through the study website. The protocol will be made available immediately following publication with no end date. |
| IPD sharing plan | After publication, individual anonymised participant data that underlie the results reported in the publication will be available to researchers upon request from Dr Carol Howell at Enteromed Ltd. Participants have provided their consent for the sharing of anonymised data for research purposes. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Protocol article | 30/01/2020 | 19/10/2021 | Yes | No | |
| Results article | 27/06/2022 | 28/06/2022 | Yes | No | |
| Protocol file | 29/06/2020 | 20/09/2022 | No | No | |
| HRA research summary | 28/06/2023 | No | No |
Additional files
Editorial Notes
20/09/2022: Uploaded protocol (not peer reviewed).
15/09/2022: The trial website and publication and dissemination plan were updated.
28/06/2022: Publication reference added.
11/01/2022: The intention to publish date was changed from 31/01/2022 to 31/03/2022.
19/10/2021: The following changes have been made:
1. Publication reference added.
2. The total final enrolment number has been changed from 647 to 439.
04/06/2021: The following changes have been made:
1. The overall trial end date has been changed from 31/07/2021 to 31/10/2021 and the plain English summary has been updated to reflect this change.
2. The intention to publish date has been changed from 31/08/2021 to 31/02/2022.
3. The total final enrolment number has been added.
29/04/2021: The recruitment end date was changed from 31/12/2020 to 21/04/2021.
13/07/2020: The trial contact details have been made publicly visible.
01/07/2020: The recruitment resumed on 01/07/2020.
23/06/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 30/10/2020 to 31/12/2020.
2. The overall end date was changed from 31/12/2020 to 31/07/2021.
3. The intention to publish date was changed from 31/07/2021 to 31/08/2021.
4. The plain English summary was updated to reflect these changes.
10/06/2020: The following changes were made to the trial record:
1. The trial website was added.
2. The recruitment end date was changed from 31/05/2020 to 30/10/2020.
23/04/2020: Due to current public health guidance, recruitment for this study has been paused.
07/01/2020: The following changes were made to the trial record:
1. The recruitment end date was changed from 01/12/2019 to 31/05/2020.
2. The overall trial end date was changed from 31/07/2020 to 31/12/2020.
3. The secondary outcome measures and exclusion criteria were updated.
03/01/2020: The trial participating centre "Wythenshawe Hospital" was added.
04/04/2019: The following changes were made to the trial record:
1. The inclusion and exclusion criteria were updated.
2. Doncaster Royal Infirmary was added as a trial participating centre.
20/02/2019: The trial participating centres were updated.
17/10/2018: The following changes were made to the trial record:
1. The interventions, secondary outcome measures and inclusion and exclusion criteria were updated.
2. The overall trial end date was changed from 31/12/2019 to 31/07/2020.
3. The recruitment start date was changed from 01/09/2018 to 15/10/2018.
4. The recruitment end date was changed from 01/06/2019 to 01/12/2019.
5. The funder was changed from Enteromed Ltd to Bioline Products s.r.o.
6. The trial participating centres were added.
11/06/2018: The following changes were made to the trial record:
1. The ethics approval details were added.
2. The recruitment start date was changed from 01/03/2018 to 01/09/2018.
