Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome (EPRIMM)

March 7, 2025 updated by: The Christie NHS Foundation Trust

Investigating the Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome to Improve the Detection and Management of Gastrointestinal (GI) Toxicity.

Eight in ten patients will develop bowel problems during radiotherapy, eg diarrhoea, pain and incontinence, half will develop difficult long-term bowel problems. It is not known why some people get bowel problems and others do not and there is no test to predict who will develop bowel problems following their treatment.

There is a link between the changes in the number and type of gut bacteria (the microbiome) in some bowel conditions and it is possible to test for these different bacteria in a simple stool sample using genetic testing. Also gut bacteria produce different gases in the stool called "volatile organic compounds" (VOCs), which can be measured in stool samples. Specific VOC patterns have been seen in other bowel conditions and small studies suggesting that there are specific VOC and gut bacteria patterns in the stool of those undergoing pelvic radiotherapy which may help to identify people who will get difficult bowel problems. Diet can change the microbiome/VOCs so diet change could improve bowel symptoms after radiotherapy.

The investigators would like to test stool samples of patients with womb, cervix or bladder cancer having pelvic radiotherapy to see if there are differences in the number/type of gut bacteria and VOCs between those who get severe bowel symptoms compared to those with mild bowel symptoms. They also want to see whether these differences in VOCs or gut bacteria can tell who will develop severe bowel symptoms during or after radiotherapy and determine the effect of diet.

The first step is to run the study on a small scale to confirm that a larger study would work. This will make sure the investigators can recruit and consent people safely and will test the best ways of measuring bowels symptoms using several questionnaire options. They will collect the information needed to work out how many people would be needed in a large trial to fully test the theory. Ultimately, the investigators would like to use differences in the number/type of gut bacteria and VOCs to find ways to better prevent and treat bowel problems after pelvic radiotherapy.

Study Overview

Status

Completed

Conditions

Detailed Description

Background 80% of patients develop GI-toxicity during pelvic radiotherapy and half develop chronic GI-toxicity. This manifests as diarrhoea, pain, bleeding and incontinence. Unlike many diseases, the triggering event, i.e. radiotherapy, is known, enabling the identification of specific pathophysiological changes. The metabolomic and microbiomic profile of patients undergoing pelvic radiotherapy and the link with GI-toxicity has not been fully explored. Studies suggest radiation alters the gut microbiome, altering microbial diversity. Higher pre-radiotherapy diversity has been seen in those with no GI symptoms with reducing diversity as GI-toxicity increases and an association between low microbial diversity and severity of chronic GI-toxicity. Dietary change can alter microbial composition. Faecal VOCs are chemicals that exist in the gaseous phase at ambient temperature and form the faecal metabolome, the result of the interaction between the gut microbiota and cell metabolism. VOCs can be identified using established techniques and unique VOCs patterns have been identified in specific GI diseases. Early data suggest differences in VOCs between patients with high vs low levels of GI-toxicity. Metabolomic and microbiomic profiling and manipulation has the potential to advance understanding of disease-related pathways to predict, prevent and treat GI-toxicity.

Rationale GI-toxicity is a significant cause of morbidity both during and after pelvic radiotherapy to the extent that it adversely affects quality of life. There is a paucity of research into this condition. The metabolomic and microbiomic profile of patients undergoing pelvic radiotherapy and the link with GI-toxicity has not been fully explored. Studies suggest radiation alters the gut microbiome, altering microbial diversity. Higher pre-radiotherapy diversity has been seen in those with no GI symptoms with reducing diversity as GI-toxicity increases and an association between low microbial diversity and severity of chronic GI-toxicity. Dietary change can alter microbial composition. Unique VOCs patterns have been identified in specific GI diseases. Early data suggest differences in VOCs between patients with high vs low levels of GI-toxicity. Metabolomic and microbiomic profiling and manipulation has the potential to advance understanding of disease-related pathways to predict, prevent and treat GI-toxicity.

By comparing samples collected pre and post radiotherapy the investigators aim to identify potential biomarkers. They are going to integrate metadata indicating a negative GI response to the therapy, i.e. GI toxicity symptoms from validated questionnaires, with microbial community data and VOCs data in order to identify markers (VOCs or bacteria) that increase with symptoms. They will also identify which species make patients more susceptible to negative outcomes by analysing the community pre-treatment.

Previous literature using culture based methods showed an increase in E. coli and Staphylococcus spp. and the investigators will determine whether they can confirm this. In terms of VOCs, they will look for markers of inflammation, e.g. aldehydes. It has been proposed that there are similarities between radiation-induced GI-toxicity and IBD, particularly Crohn's disease, therefore it would be interesting to see whether there is a similar dysbiosis of the microbial community and VOCs profile to that observed in Crohn's disease, i.e. whether decreased species diversity, increased Bacteroides species and Enterobacteriaceae coupled with a decrease in Faecal bacterium are also observed in patients with severe GI toxicity symptoms.

Potential interventions to modify the gut microbiome, e.g. diet, pre/probiotics, synthetic faecal microbiota transplantation, are in wide clinical research use currently in other related clinical areas, e.g. inflammatory bowel disease, and would be the types of interventions that may be indicated by information from this work and the subsequent definitive study.

The objectives of the subsequent definitive study are as follows:

  1. Determine the differences in VOC profile/microbiome in patients with the most severe vs least severe GI-toxicity at 4 weeks and 6 months.
  2. Determine the differences in VOC profile/microbiome at baseline in patients who develop the most severe vs least severe GI-toxicity at 4 weeks and 6 months.
  3. Characterise disease-related pathways for GI-toxicity to identify potential therapeutic targets, including dietary.

Study Type

Observational

Enrollment (Actual)

18

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Eligible patients will be identified from new patient referrals to oncology clinics for pelvic radiotherapy to treat cervix, endometrial or bladder cancer

Description

Inclusion Criteria:

  • Pelvic radiotherapy-cervix/endometrial/bladder cancer.
  • ≥18 years.
  • Able to consent.
  • Able to complete questionnaires.

Exclusion Criteria:

  • Pre-existing GI disease
  • Abdominopelvic surgery within preceding 4 weeks

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Other
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
EPRIMM study participants
No intervention: Questionnaires, food diaries and stool sample.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of recruitment
Time Frame: 12 months
Recruitment rates: can we achieve sufficient recruitment to the study? Are patients willing to participate?
12 months
Acceptability of recruitment
Time Frame: 12 months
Acceptability of recruitment process to patient cohort measured using internally generated non-validated questionnaire led by the research nurse
12 months
Patient experience of study
Time Frame: 6 months
Experience of the study process by patient cohort measured using internally generated non-validated questionnaire led by the research nurse
6 months
Stool sample collection
Time Frame: 6 months
Practicality and acceptability of obtaining stool samples for patient cohort measured using internally generated non-validated questionnaire led by the research nurse
6 months
Attrition rates
Time Frame: 18 months
Rate of patient leaving the study before completing
18 months
Reason for attrition
Time Frame: 18 months
Reason for patient leaving the study before completing
18 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acceptability of questionnaires/food diaries
Time Frame: 6 months
Acceptability of questionnaires and food diaries to patient cohort measured using internally generated non-validated questionnaire led by the research nurse
6 months
Completion of information
Time Frame: 6 months
Proportion of patients who complete the study eg rate of attrition of patients and rate of missing data items
6 months
The number of participants required to take part in a larger multicentre trial which will identify microbiome/VOC profiles which confer risk of GI toxicity
Time Frame: 24 months
To identify microbiome (diversity or composition) or VOCs profile that confers risk of GI-toxicity and that is associated with participants greater severity of GI-toxicity in response in response to radiotherapy in the acute and chronic phases
24 months
The number of participants required to take part in a larger multicentre trial which will identify potential therapeutic targets from metabolomic and microbiomic profiling
Time Frame: 24 months
To use metabolomic and microbiomic profiling to further understand the pathophysiology of GI-toxicity to identify potential therapeutic targets for treatment and/or prevention, including dietary targets
24 months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Microbiome data (DNA reads)
Time Frame: 24 months
Obtain initial data regarding microbiome (diversity or composition) associated with risk of GI-toxicity and that is associated with greater severity of GI-toxicity in response in response to radiotherapy in the acute and chronic phases
24 months
VOC profile by solid-phase microextraction followed by gas chromatography-mass spectrometry SPME-GC/MS
Time Frame: 24 months
Obtain initial data (peak area/metabolite(VOC)/sample) regarding VOCs profile associated with risk of GI-toxicity and that is associated with greater severity of GI-toxicity in response in response to radiotherapy in the acute and chronic phases.
24 months
Metabolomic profiling by SPME-GC/MS
Time Frame: 24 months
To use metabolomic profiling to further understand the pathophysiology of GI-toxicity to identify potential therapeutic targets for treatment and/or prevention, including dietary targets
24 months
Microbiomic profiling by bacterial 16S rRNA metabarcoding sequencing
Time Frame: 24 months
To use microbiomic profiling ( data table containing number of reads/species/sample) to further understand the pathophysiology of GI-toxicity to identify potential therapeutic targets for treatment and/or prevention, including dietary targets
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The Christie NHS Foundation Trust

Collaborators

University of Liverpool
University of Manchester
Wythenshawe Hospital

Investigators

  • Principal Investigator: Caroline Henson, MBBS PhD, The Christie NHS Foundation Trust

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 5, 2021

Primary Completion (Actual)

July 21, 2023

Study Completion (Actual)

July 21, 2023

Study Registration Dates

First Submitted

May 26, 2021

First Submitted That Met QC Criteria

August 5, 2021

First Posted (Actual)

August 9, 2021

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

March 7, 2025

Last Verified

October 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 21_DOG13_32

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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