Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome

NCT04995809 | Completed

• 1 other identifier: 21_DOG13_32
• Study Type: observational
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms

Keywords

Pelvic radiotherapy; Microbiota; Metabolome; Gastrointestinal toxicity

Outcome Measures

Primary Outcomes (6)

• Rate of recruitment

  Recruitment rates: can we achieve sufficient recruitment to the study? Are patients willing to participate?

  12 months

• Acceptability of recruitment

  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

  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

  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

  Rate of patient leaving the study before completing

  18 months

• Reason for attrition

  Reason for patient leaving the study before completing

  18 months

Secondary Outcomes (4)

• Acceptability of questionnaires/food diaries

  6 months

• Completion of information

  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

  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

  24 months

Other Outcomes (4)

• Microbiome data (DNA reads)

  24 months

• VOC profile by solid-phase microextraction followed by gas chromatography-mass spectrometry SPME-GC/MS

  24 months

• Metabolomic profiling by SPME-GC/MS

  24 months

Study Arms (1)

EPRIMM study participants

No intervention: Questionnaires, food diaries and stool sample.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• The Christie NHS Foundation Trust: lead
• University of Liverpool: collaborator
• University of Manchester: collaborator
• Wythenshawe Hospital: collaborator

Study Sites (1)

Louise James

Manchester, M20 4GJ, United Kingdom

Location

Related Publications (23)

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  PMID: 18760593 BACKGROUND

• Andreyev J. Gastrointestinal symptoms after pelvic radiotherapy: a new understanding to improve management of symptomatic patients. Lancet Oncol. 2007 Nov;8(11):1007-17. doi: 10.1016/S1470-2045(07)70341-8.

  PMID: 17976611 BACKGROUND

• Gami B, Harrington K, Blake P, Dearnaley D, Tait D, Davies J, Norman AR, Andreyev HJ. How patients manage gastrointestinal symptoms after pelvic radiotherapy. Aliment Pharmacol Ther. 2003 Nov 15;18(10):987-94. doi: 10.1046/j.1365-2036.2003.01760.x.

  PMID: 14616164 BACKGROUND

• Nam YD, Kim HJ, Seo JG, Kang SW, Bae JW. Impact of pelvic radiotherapy on gut microbiota of gynecological cancer patients revealed by massive pyrosequencing. PLoS One. 2013 Dec 18;8(12):e82659. doi: 10.1371/journal.pone.0082659. eCollection 2013.

  PMID: 24367534 BACKGROUND

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  PMID: 22439602 BACKGROUND

• Kim YS, Kim J, Park SJ. High-throughput 16S rRNA gene sequencing reveals alterations of mouse intestinal microbiota after radiotherapy. Anaerobe. 2015 Jun;33:1-7. doi: 10.1016/j.anaerobe.2015.01.004. Epub 2015 Jan 16.

  PMID: 25600706 BACKGROUND

• Manichanh C, Varela E, Martinez C, Antolin M, Llopis M, Dore J, Giralt J, Guarner F, Malagelada JR. The gut microbiota predispose to the pathophysiology of acute postradiotherapy diarrhea. Am J Gastroenterol. 2008 Jul;103(7):1754-61. doi: 10.1111/j.1572-0241.2008.01868.x. Epub 2008 Jun 28.

  PMID: 18564125 BACKGROUND

• Goudarzi M, Mak TD, Jacobs JP, Moon BH, Strawn SJ, Braun J, Brenner DJ, Fornace AJ Jr, Li HH. An Integrated Multi-Omic Approach to Assess Radiation Injury on the Host-Microbiome Axis. Radiat Res. 2016 Sep;186(3):219-34. doi: 10.1667/RR14306.1. Epub 2016 Aug 11.

  PMID: 27512828 BACKGROUND

• Wang A, Ling Z, Yang Z, Kiela PR, Wang T, Wang C, Cao L, Geng F, Shen M, Ran X, Su Y, Cheng T, Wang J. Gut microbial dysbiosis may predict diarrhea and fatigue in patients undergoing pelvic cancer radiotherapy: a pilot study. PLoS One. 2015 May 8;10(5):e0126312. doi: 10.1371/journal.pone.0126312. eCollection 2015.

  PMID: 25955845 BACKGROUND

• Reis Ferreira M, Andreyev HJN, Mohammed K, Truelove L, Gowan SM, Li J, Gulliford SL, Marchesi JR, Dearnaley DP. Microbiota- and Radiotherapy-Induced Gastrointestinal Side-Effects (MARS) Study: A Large Pilot Study of the Microbiome in Acute and Late-Radiation Enteropathy. Clin Cancer Res. 2019 Nov 1;25(21):6487-6500. doi: 10.1158/1078-0432.CCR-19-0960. Epub 2019 Jul 25.

  PMID: 31345839 BACKGROUND

• Cui M, Xiao H, Li Y, Zhou L, Zhao S, Luo D, Zheng Q, Dong J, Zhao Y, Zhang X, Zhang J, Lu L, Wang H, Fan S. Faecal microbiota transplantation protects against radiation-induced toxicity. EMBO Mol Med. 2017 Apr;9(4):448-461. doi: 10.15252/emmm.201606932.

  PMID: 28242755 BACKGROUND

• David LA, Maurice CF, Carmody RN, Gootenberg DB, Button JE, Wolfe BE, Ling AV, Devlin AS, Varma Y, Fischbach MA, Biddinger SB, Dutton RJ, Turnbaugh PJ. Diet rapidly and reproducibly alters the human gut microbiome. Nature. 2014 Jan 23;505(7484):559-63. doi: 10.1038/nature12820. Epub 2013 Dec 11.

  PMID: 24336217 BACKGROUND

• Reade S, Mayor A, Aggio R, Khalid T, Pritchard DM, Ewer AK, et al. Optimisation of Sample Preparation for Direct SPME-GC-MS Analysis of Murine and Human Faecal Volatile Organic Compounds for Metabolomic Studies. J Anal Bioanal Tech. 2014;5(2).

  BACKGROUND

• Xu X, Xu P, Ma C, Tang J, Zhang X. Gut microbiota, host health, and polysaccharides. Biotechnol Adv. 2013 Mar-Apr;31(2):318-37. doi: 10.1016/j.biotechadv.2012.12.009. Epub 2012 Dec 30.

  PMID: 23280014 BACKGROUND

• Hough R, Archer D, Probert C. A comparison of sample preparation methods for extracting volatile organic compounds (VOCs) from equine faeces using HS-SPME. Metabolomics. 2018;14(2):19. doi: 10.1007/s11306-017-1315-7. Epub 2018 Jan 4.

  PMID: 29367839 BACKGROUND

• Mikami T, Aoki M, Kimura T. The application of mass spectrometry to proteomics and metabolomics in biomarker discovery and drug development. Curr Mol Pharmacol. 2012 Jun;5(2):301-16. doi: 10.2174/1874467211205020301.

  PMID: 22122469 BACKGROUND

• Probert CS. Role of faecal gas analysis for the diagnosis of IBD. Biochem Soc Trans. 2011 Aug;39(4):1079-80. doi: 10.1042/BST0391079.

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• Probert CS, Ahmed I, Khalid T, Johnson E, Smith S, Ratcliffe N. Volatile organic compounds as diagnostic biomarkers in gastrointestinal and liver diseases. J Gastrointestin Liver Dis. 2009 Sep;18(3):337-43.

  PMID: 19795029 BACKGROUND

• Probert CS, Jones PR, Ratcliffe NM. A novel method for rapidly diagnosing the causes of diarrhoea. Gut. 2004 Jan;53(1):58-61. doi: 10.1136/gut.53.1.58.

  PMID: 14684577 BACKGROUND

• Covington JA, Wedlake L, Andreyev J, Ouaret N, Thomas MG, Nwokolo CU, Bardhan KD, Arasaradnam RP. The detection of patients at risk of gastrointestinal toxicity during pelvic radiotherapy by electronic nose and FAIMS: a pilot study. Sensors (Basel). 2012 Sep 26;12(10):13002-18. doi: 10.3390/s121013002.

  PMID: 23201982 BACKGROUND

• Sokol H, Adolph TE. The microbiota: an underestimated actor in radiation-induced lesions? Gut. 2018 Jan;67(1):1-2. doi: 10.1136/gutjnl-2017-314279. Epub 2017 May 4. No abstract available.

  PMID: 28473631 BACKGROUND

• Stringer AM, Al-Dasooqi N, Bowen JM, Tan TH, Radzuan M, Logan RM, Mayo B, Keefe DM, Gibson RJ. Biomarkers of chemotherapy-induced diarrhoea: a clinical study of intestinal microbiome alterations, inflammation and circulating matrix metalloproteinases. Support Care Cancer. 2013 Jul;21(7):1843-52. doi: 10.1007/s00520-013-1741-7. Epub 2013 Feb 10.

  PMID: 23397098 BACKGROUND

• Ferreira MR, Muls A, Dearnaley DP, Andreyev HJ. Microbiota and radiation-induced bowel toxicity: lessons from inflammatory bowel disease for the radiation oncologist. Lancet Oncol. 2014 Mar;15(3):e139-47. doi: 10.1016/S1470-2045(13)70504-7.

  PMID: 24599929 BACKGROUND

Related Links

• Lay summary of EPRIMM results

MeSH Terms

Conditions

Urinary Bladder Neoplasms; Uterine Cervical Neoplasms; Endometrial Neoplasms

Condition Hierarchy (Ancestors)

Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Urinary Bladder Diseases; Urologic Diseases; Male Urogenital Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Genital Diseases

Study Officials

• Caroline Henson, MBBS PhD

  The Christie NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2021
• First Posted: August 9, 2021
• Study Start: July 5, 2021
• Primary Completion: July 21, 2023
• Study Completion: July 21, 2023
• Last Updated: March 12, 2025

Record last verified: 2024-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)