IMPuLCE (Intestinal Microbiota Product in Liver Cirrhosis and Encephalopathy)
Research type
Research Study
Full title
A Multicentre, Randomised, Double-blind Placebo-controlled, Phase II Study to Evaluate the Safety, Tolerability and Dose of Dried Intestinal Microbiota Medicinal Product, EBX-102 in Liver Cirrhosis Subjects (IMPuLCE)
IRAS ID
1005961
Contact name
Julie Bakobaki
Contact email
Sponsor organisation
EnteroBiotix Limited
ISRCTN Number
ISRCTN11352030
Research summary
Research Summary
EnteroBiotix thanks all patients who volunteered for this study, as well as their families and carers for their support.
Study title, who, where and when:
IMPuLCE (Intestinal Microbiota Product in Liver Cirrhosis and Encephalopathy)
This study was carried out by EnteroBiotix, the developers of the medicine EBX-102, between May 2023 and January 2024. Doctors and research teams at centres across the UK looked after the patients taking part. These centres received funding from EnteroBiotix to cover the costs of treatment, tests and study procedures.Why was the research needed?
Cirrhosis is a serious condition where long-term damage leads to scarring of the liver, stopping it from working properly. As the disease progresses, people may develop symptoms such as tiredness, confusion, behaviour changes or difficulty concentrating. These brain-related problems are known as hepatic encephalopathy.
There is currently no cure for cirrhosis, so treatments that can slow or improve the condition are needed. Everyone has a natural community of microorganisms in their gut (“gut bugs”) that help digestion and support overall health. People with cirrhosis often have an unhealthy balance of these bugs compared with healthy individuals.
Research suggests that restoring healthier gut microorganisms may help improve some symptoms. Intestinal microbiota transfer (IMT) involves giving patients specially prepared gut bugs from healthy donors. EBX-102, the IMT used in this study, is made from donations from carefully screened healthy UK volunteers. Each donation is extensively tested to ensure safety.What were the main questions studied, who participated and what treatments were taken?
The study aimed to find out whether the IMT was safe for people with cirrhosis and whether it could successfully change the gut microorganisms of patients. Forty people volunteered, and after assessment, twenty-eight were able to take part.The study had two planned parts.
Part 1 included patients with early-stage liver cirrhosis who received either two capsules of IMT or dummy capsules with no bugs. After reviewing safety results, a second group received ten capsules of IMT or dummy capsules.
Part 2 was intended to include patients whose cirrhosis was slightly more severe. Some of these patients might have had early signs of encephalopathy (changes in their thinking and behaviour). The aim was to see whether the IMT (or dummy capsules) could improve test results related to their brain function.After reviewing results from part 1, the study sponsor decided that enough information on safety had been collected, so part 2 did not continue.
What medical problems (adverse reactions) did the participants have?
Most medical problems were mild, mainly involving discomfort in the belly or opening of the bowels.
One patient receiving the dummy capsule had a very bad cough and sore throat. Other effects on patients were mostly mild (no treatment required; about 2 out 3 problems), and some were moderate but improved with simple treatment (about 1 out of 6). No patient needed to stay in hospital (or caused further problems requiring urgent treatment). All patients stayed alive throughout the study. The higher dose did not appear to cause more problems than the lower dose or the dummy capsules.What happened during the study and what were the results?
The study showed that EBX-102 appeared safe to give to patients with cirrhosis by not causing problems that would worry the patients or their doctors.
Patients in part 1 had normal test results for thinking and behaviour at the start of the study, and these did not change. As part 2 did not go ahead, the study did not include patients with cirrhosis who were more unwell. Samples from patients who received IMT drug showed that some of the bugs in the IMT product settled in their gut. Overall, the study demonstrated that IMT can be safely given to people with liver disease and provided helpful information to guide future research.The aim of the study is to assess the safety and tolerability of a potential treatment, called EBX-102, for patients with liver cirrhosis and to learn about the effects of EBX-102 on gut microbiota diversity. The main function of the liver is to remove toxins from the body, such as ammonia. In patients with cirrhosis, the build up of ammonia can lead to significant illness which affects the brain function and can lead to irreversible brain damage, coma or death. It has been shown that imbalanced gut microbial function plays a critical role in the development and worsening of cirrhosis. Patients with cirrhosis are also more susceptible to infections, are frequently prescribed antibiotics and have multiple hospitalisations. Current treatments such as lactulose and rifaximin help to eliminate ammonia from the body but there are side effects associated with their use. Medicinal approaches to correcting the gut imbalance are now of high interest to treat chronic liver cirrhosis and prevent the symptoms of raised ammonia levels, that can lead to hepatic encephalopathy (HE). EBX-102 has the potential to improve microbial diversity. EBX-102 capsules contain communities of dried, intestinal microorganisms taken from carefully screened pooled human stool samples. EBX-102 will be given as a single dose soon after randomisation under strict observation and thereafter participants are followed for 12 weeks to assess safety, tolerability and microbiota dynamics. The study is a phase II, multicentre, randomised, double-blind placebo-controlled trial. The study will involve two parts (A and B). At the end of Part A, a Dose Selection Review (DSR) meeting will occur to determine the dose for part B. Safety will be monitored by a Safety Review Team and assessments will include: Documentation of adverse events, blood and urine tests, stool sample tests, ECG, HE assessments and questionnaires.
REC name
East Midlands - Leicester South Research Ethics Committee
REC reference
22/EM/0259
Date of REC Opinion
21 Feb 2023
REC opinion
Further Information Favourable Opinion