Enterosgel in the treatment of Irritable Bowel Syndrome with Diarrhoea
Research type
Research Study
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
IRAS ID
230930
Contact name
Yan Yiannakou
Contact email
Sponsor organisation
Enteromed Ltd
ISRCTN Number
ISRCTN17149988
Duration of Study in the UK
1 years, 9 months, 1 days
Research summary
Summary of Research
Enterosgel® in the treatment of Irritable Bowel Syndrome with Diarrhoea in adultsIrritable Bowel Syndrome (IBS) is a common condition 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. IBS is 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. There is a need for novel treatments, including drug-free alternatives, which are easy and safe to use in different patient groups. Currently available drug-free treatments include Enterosgel®, which is an intestinal adsorbent approved for use in patients with IBS-D and is available over-the-counter in the UK. Previous studies suggest 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®.
This study aims to recruit 430 adult participants with IBS-D, from approximately 30 medical practices and outpatient clinics in the UK. The goal is to investigate whether Enterosgel® can improve IBS-D symptoms, including diarrhoea and abdominal pain, and is well-tolerated. The study will also investigate the impact of Enterosgel® on the quality of life, work productivity and activity and general health, and evaluate whether Enterosgel® has long-term effects. The study will involve four visits and one phone call over 26 weeks. During the study, the participants will complete questionnaires related to IBS and general health, and a daily study diary over 18 weeks. In the first treatment phase, half of the patients will receive Enterosgel® and half will receive a placebo for 8 weeks. In the second treatment phase, all patients will receive Enterosgel® for 8 weeks.
The study is funded by Enteromed Ltd.
Summary of Results
Short study title: Enterosgel in the treatment of irritable bowel syndrome with diarrhoeaFull study 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)
IRAS ID: 230930
REC reference: 18/NE/0023
MHRA Reference: CI/2018/0033
NIHR portfolio number: GAST 34032
ISRCTN number: ISRCTN17149988This study aims to improve treatment available for IBS-D. Thank you to all the patients and investigators that took part or contributed towards the RELIEVE IBS-D study and made this study possible.
What treatments did the participants receive?
Enterosgel: This is a tasteless gel that is mixed with water and patient’s drink. It is a type of treatment called an intestinal adsorbent and works in the gut by capturing harmful substances that can cause diarrhoea and removing them from the body in the stool. Patients received a tube containing the gel mixed in water, which they mixed into a glass of water and drank.
Placebo: A tube containing water only, which mixed into a glass of water looks and tastes the same as the treatment.
Randomisation:
• People with IBS-D were put into 2 groups by chance (called randomisation).
• Each group were given either Enterosgel or the placebo.
• This makes it fairer to compare the results from the 2 groups.
Blinding: This study was also “double-blinded”. This means that both the patients and the doctors did not know if the treatment or the placebo was given. This was done so that the test results were not affected by patients and doctors knowing which group they were in, placebo or Enterosgel.General information
Abstract
• Purpose of the study: To see if Enterosgel helps to treat the main symptoms of people with irritable bowel syndrome with diarrhoea (IBS-D).
• What was tested: Enterosgel was compared to placebo. This study monitors the safety and effectiveness of the treatment.
• People taking part: 440 people aged 16 to 75 years, diagnosed with irritable bowel syndrome with diarrhoea (IBS-D) took part in this UK trial.
• Results: More people with IBS-D who took Enterosgel had improvement in their symptoms of diarrhoea, abdominal pain, stool frequency, bloating and urgency, than those who took placebo.
• Safety: In this study, researchers found that people who took Enterosgel had slightly fewer, but the same type of side effects as the placebo.
• Conclusion:
o Patients who took Enterosgel had an improvement in their main symptoms of IBS-D.
o Slightly fewer patients in the Enterosgel group reported side effects than in the placebo group.Where the study took place: The study began recruiting patients with IBS-D in November 2018 and ended in October 2021. Patients joined from GP surgeries, hospitals and a private clinic, all located in England and a virtual UK site (patients did not attend this site but had online visits).
Why was this study done: To provide more information about safety and whether Enterosgel improved the main symptoms of people with IBS-D, after it had been approved for sale in Europe.
What were the main questions: To see if:
• Enterosgel helps to treat the main symptoms of diarrhoea and abdominal pain in people with IBS-D.
• Enterosgel improves other IBS-D symptoms, patient quality of life and if it gives patients adequate relief of their symptoms.
• Enterosgel is a safe treatment compared to a placebo.
Who took part in the study:
• 617 patients aged 16 to 75 years with IBS-D recorded their IBS-D symptoms in an electronic diary and in questionnaires.
• After 2 weeks if patients had suitable IBS-D symptoms they were recruited into the study.
How were patients involved in the study design: Patients were involved at all stages of the study. They helped in the following:
• design of the study
• checked patient information leaflets
• testing the electronic patient diary
• setting up the virtual study site
• participants from the study also took part in an interactive webinar where they learnt about the study results and could ask the study team any questions.
What happened during the study: 440 patients were recruited and given either Enterosgel or placebo, which they took for 8 weeks (Double-blind phase).
Everyday patients reported the following;
• their symptoms
• doses of the Enterosgel or placebo they took
• any side effects
After 8 weeks all patients knew they then received Enterosgel in this Open label phase and reported the same things for another 8 weeks.
After 16 weeks if patients reported adequate relief of their IBS-D symptoms, they were then asked some questions about their symptoms and Enterosgel use.
What medical problems (side effects) did the participants have?
Side effects are unwanted medical events that happen during the study and are reported by the trial doctor or nurse (investigators) as they may be related to the treatment.Side effects reported in this study:
• Slightly more patients in the placebo group (9%) reported related side effects than in the Enterosgel group (7%).
• The most common side effect reported was feeling sick (nausea) which was reported by 8 patients out of 214 (4%) in the Enterosgel group and 8 patients out of 213 in the placebo group (4%).
• The next most common side effects were bloating reported by 3% of patients in the Enterosgel group and 1% of placebo patients.
• Also reported was Abdominal pain in 1% of Enterosgel patients and 2% of placebo patients.
• No serious bad reactions, which are life threatening or require the patient to go to hospital, were related to treatment with Enterosgel.What were the results of the study?
Treatment groups: In this study during the double-blind phase the patients were divided equally into 2 groups. The treatment group were given Enterosgel and the placebo (control) group were given placebo for 8 weeks.
What was the primary endpoint: The primary endpoint is the main result that is measured to see if the treatment has worked.
• In this study the primary endpoint measured the percentage of patients that had a 30% decrease in their abdominal pain and a 50% reduction in days with a loose stool, during at least 4 out of the 8 weeks double-blind phase.• The Enterosgel group had a higher percentage of patients (37%) that were positive for the primary endpoint (showed a decrease in both abdominal pain and stool consistency) compared to the placebo (24%).
• This difference between the groups is not likely to be by chance (a 2 in 1000 chance).
Other secondary outcomes: The study also measured other secondary outcomes to see if the treatment made a difference to other IBS-D symptoms.
• The Enterosgel group had a higher percentage of patients (49%) with an improvement in their stool consistency compared to the placebo group (33%).
• The Enterosgel group also had a higher percentage of patients (53%) with a reduction of abdominal pain compared to 40% to the placebo group.
• The average number of stools per day, and the average bloating and urgency scores reported by patients, also improved more in the Enterosgel group than in the placebo group.
• This difference in symptoms between the groups was bigger for the last 4 weeks of the double-blind phase.
Adequate relief of IBS-D symptoms:
• The proportion of patients reporting “adequate relief” of their IBS-D symptoms was greater in the patients who took Enterosgel compared to placebo.
• This was also higher in the Enterosgel group for week 5-8 of the double-blind phase and continued to improve further in the open-label phase when all patients took Enterosgel.
• At the end of the open-label phase 264 patients out of 349 (76%) reported adequate relief of their symptoms.
• These patients continued onto the further 8 week follow up phase.
• 186 out of 253 (74%) of these patients who completed the follow-up phase said they had an increased or maintained treatment benefit.All the results from the study: These can be found by clicking on the link below, which will take you to the published full results in the scientific journal GUT.
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DPbf8m0AMf80LgKkJSwbdGDh7w8uWMMopN98WAYQI0y36H9tcTAxqcH3cZ-2FyPWG4Gu0kyrWNm10de7HBD-2FOkzDQ-3D-3DvZIi_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJSrKoF36M6g43gJfLE-2B01GDNwaA0VLwnSNR4Pv4AuKq6AHW-2BQLhiaC3HjWNKhMoKbdidxF7IoJghx6DnYkGrhsjuncv4GHOcJQlSiSrtQVIcH6syOBNJpZwadDjxx1y-2BW3sJmemS2oXrWqWhlenm00plfqxgo9t-2BUT2K4KI-2BZAyg-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C567d76832f8a4a6e16fa08da96fd6d21%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988312446611073%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=SDLnevvXWzXlPGmRYlMLfx2FvlSYewQVbu68Ii0Yo98%3D&reserved=0
The study results are also being presented to doctors, nurses and pharmacists at conferences and events throughout the UK.Conclusion of the study: In this study more people with IBS-D who took Enterosgel had improvement in their symptoms of diarrhoea, abdominal pain, stool frequency, bloating and urgency, than those who took placebo. Slightly fewer patients in the Enterosgel group reported side effects than in the placebo group. The type of side effects reported were similar in both groups, with nausea being the most common.
How has this study helped patients and researchers?
Patients: There are many people with irritable bowel syndrome with diarrhoea in the UK. There are not enough different types of treatment to help these people reduce their symptoms which cause much suffering. This study found that Enterosgel can help some people with IBS-D to reduce their most common symptoms.The results from this study apply to people aged 16 and above with the diarrhoea form of irritable bowel syndrome. However, this summary only shows the results from this one study. Other studies may find different results. Patients should not change their treatment based on the results of this study without first talking to their doctor or healthcare professional.
Researchers: The findings from this study offer a new treatment that doctors can recommend to people with IBS-D, to try and see if it can help them manage their symptoms. The results from this study have allowed researchers to better understand which symptoms Enterosgel can improve in people with IBS-D. Although the results from this study showed that Enterosgel can help some people with IBS-D. There were a few limitations to this study, which may make a difference in how researchers look at the results.
We used an official guideline to diagnose people with IBS-D, which may have stopped people with milder symptoms from being able to join the study. We used a water placebo as the control treatment to compare with Enterosgel mixed in water. These were not identical, but it was not possible to make a placebo the same as Enterosgel. We did not ask participants if they knew which treatment they had been taking during the double-blind phase. It may be that some knew which treatment they had taken (became unblinded) once they started the open-label phase when all patients took Enterosgel. We tried to limit this from happening by not allowing people to join the study that had used Enterosgel before.
Are any further studies planned?
Further clinical studies with Enterosgel are planned, for similar medical conditions that cause people to have long-term (chronic) diarrhoea. These include bile acid malabsorption and pelvic radiation disease. A study in children under 5 years with short-term (acute) diarrhoea will soon begin in The Gambia.Where can I learn more about this study?
To learn more about this study, you can find more information on the Sponsors website. Here you can watch the webinar where study patients were the first people to learn about the results and were able to ask questions to the lead clinician on the study.Website: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbUG3dxt3-2F58QLvcXvJjF5UQT6fKm1XZJStR3gt5anG1VeqmRN7T6YlJ-2BIHK9vtTf4A-3D-3Dh1rx_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJSrKoF36M6g43gJfLE-2B01GK-2FG-2FhAdSZmDMfA5Th8j1QLRqT33lejAHImSEHB90KFvKYZyxT0lhDKwQGRrmeXmBfqtliFusSDT2XLMI6dkHdCJKGdfqG4wo5u6HgYjXGeNlVkX7jzlzmbaOeoQHKvtlvXpOhlCuiuqiQlzF91UWYA-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C567d76832f8a4a6e16fa08da96fd6d21%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988312446611073%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=hUJDD8czoOfMxMwZ6736ZPjZhe9ZEI1%2FyQyXoFI8Efs%3D&reserved=0
To read the full study results published in an article in the scientific journal GUT, you can follow the link below.
Results article: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DPbf8m0AMf80LgKkJSwbdGDh7w8uWMMopN98WAYQI0y36H9tcTAxqcH3cZ-2FyPWG4Gu0kyrWNm10de7HBD-2FOkzDQ-3D-3DJX0Z_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJSrKoF36M6g43gJfLE-2B01GwAg7b0GYYY-2B4109ACxmilCrvsGpBWQ1lqMeGNcSK4EGhswFCGMEI8h5M1KgR2Rm4DOqERF92S7hx4lhiX5rDol5WYas5AtLJ-2FOh6s-2FHAPS5YRBCTlouSIgOckZ3KdKK-2FFpOXolPQfJoH6drYljHXaQ-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C567d76832f8a4a6e16fa08da96fd6d21%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988312446611073%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=bPHPihDTk0kazgnbVCk9WcpIUogdX%2FQizy3968Hy6JQ%3D&reserved=0
To learn about the study design, you can follow the link below to an article published in the scientific journal TRIALS.
Study design article: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbSR4UtDaw26hLp3Bfks-2F7CxxSLwpqN31njVz0in-2BYCk5ONUMbOtqEBVtBFSA-2F-2FjHgVKRdHWWeNKvhSOpS67uxcJFVxkbfGhKlAHTgnn-2BSzHxDmFy_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJSrKoF36M6g43gJfLE-2B01G9IoeTQIYCVQWc7tIY6BjuL4gkmiISQzwGJWJfgvzXRRRyYH9PIdClDvnrwLl-2F-2FFomLIZ27ndo9VR80pB-2B8azaHa9VwL1VSyUaAQMFpXz80i048PgQ7c0yH2xL0Wv21TiYffGQ3LFLrVnZ91Fz-2FoE0A-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C567d76832f8a4a6e16fa08da96fd6d21%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988312446611073%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=Uo%2FEqs9sr13P6g1KMuaPuOmkSvOo0ct9d4kU7y9PdRU%3D&reserved=0
More information may also be available by going to:
ISRCTN Clinical trials registry:
https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbdFELGNEN9gmUgjOT6gsimhhDsxmcgqV-2F1hXAI2uglRW0FA0_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJSrKoF36M6g43gJfLE-2B01G4a37-2B88KM-2F5JAUJx-2BCODJP1AQ-2Bkqrj7e0kRvC9BzUbVypjXSFVhyUiVb2rNJzXzpP3mkgpRFK5vq6HBHH6njG1KdiV4-2B-2BbAPYu8VaPG8oEoIjsELujBjvu7JOrAfX9yvzZkI4b3ueAtT5LgUnzvCNw-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C567d76832f8a4a6e16fa08da96fd6d21%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988312446611073%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=3tIhRCEOW6pLaO3ci9O8djJPqx8B7EQGgfOemQhSwSQ%3D&reserved=0Who sponsored the study and how can I contact them?
The sponsor of this study was Enteromed Ltd. We would like to thank everyone who took part in the study.The contact details of the sponsor can be found below:
Website: https://eur03.safelinks.protection.outlook.com/?url=https%3A%2F%2Fu2790089.ct.sendgrid.net%2Fls%2Fclick%3Fupn%3DXv3JSvJ-2B3M71ppf7N9agbUG3dxt3-2F58QLvcXvJjF5UQXorlYMQBkYe8P5nAtJiLezRpA_E1aO2-2BZlVOSJJV-2FajQqskegTd6IRomHYTi-2Fbt8SH3YJSrKoF36M6g43gJfLE-2B01Gn0bALE64csORKb8jz5NbaG3p5fS1iwubG5xS0SRvoWzu1lnopwqmDmBUHnneYDMoMvmSA04jIaLS2lL-2FL0f9We3U5NVVnJr8vbxMrHa4rtWQLhFuLj02f-2BJv5J8CIfCuti4I-2F2TeAnRpATrRVC0g0Q-3D-3D&data=05%7C01%7Capprovals%40hra.nhs.uk%7C567d76832f8a4a6e16fa08da96fd6d21%7C8e1f0acad87d4f20939e36243d574267%7C0%7C0%7C637988312446611073%7CUnknown%7CTWFpbGZsb3d8eyJWIjoiMC4wLjAwMDAiLCJQIjoiV2luMzIiLCJBTiI6Ik1haWwiLCJXVCI6Mn0%3D%7C3000%7C%7C%7C&sdata=oZSvVRrJGVtZU25grIbkgsL3%2F2UDdKXW3lh2KClErzk%3D&reserved=0
Email: info@enteromed.co.ukThe study was overseen by the Chief Investigator Professor Yan Yiannakou, Consultant Neurogastroenterologist from County Durham and Darlington NHS Foundation Trust, and Director of the NIHR Patient Recruitment Centre: Newcastle.
The study was funded by Bioline Products s.r.o, the legal manufacturer of Enterosgel in the EU. The funder had no role in the collection, analysis, data interpretation or writing of the study report.
Competing interests: Enteromed Ltd the study Sponsor, are the exclusive distributor of Enterosgel in the UK. The chief investigator and was recompensed with fees paid to his institution for his work on the study. The other institutions for each site investigator were paid the recommended NIHR fees for participation in clinical trials.
REC name
North East - Tyne & Wear South Research Ethics Committee
REC reference
18/NE/0023
Date of REC Opinion
1 Feb 2018
REC opinion
Favourable Opinion