capsules containing probiotic powder and corn starch

Capsules placebo

Capsules probiotic powder and corn starch

The aim of the current Project is to study the efficacy of a probiotic Product in reducing the symptoms of gastrointestinal toxicity linked to the irradiation of gynecologic cancer.

Probiotics in Radiation-treated Gynecologic Cancer

Probi AB

Neoplasms

All Conditions

Digestive System Diseases

Gland and Hormone Related Diseases

Symptoms and General Pathology

Rare Diseases

Adenocarcinoma

Pancreatic Neoplasms

Hemorrhage

Gastrointestinal Hemorrhage

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Pancreatic Cancer

The patients take Albis® 2T orally twice a day during the period between start day of concurrent chemoradiotherapy and 1 month after the treatment. During the period receiving radiation, the patient are prescribed the medication by the 2 weeks, and after radiation, they receive the 1 month's medication.

Albis®

The patients take placebo 2T orally twice a day during the period between start day of concurrent chemoradiotherapy and 1 month after the treatment. During the period receiving radiation, the patient are prescribed the medication by the 2 weeks, and after radiation, they receive the 1 month's medication.

Placebo

Pancreatic ductal adenocarcinoma is the fourth cause of death in the Western world. About 40% of pancreatic cancer patients were diagnosed as locally advanced unresectable status without distant metastasis. Concurrent chemoradiotherapy (CCRT) was a reasonable treatment modality for locally advanced pancreatic cancer. However, several adverse events of chemoradiation could lead unfavorable treatment results, which included unique gastrointestinal (GI) toxicities, such as ulcer and hemorrhage in the stomach and duodenum that are included in the radiation field. According to the study in the investigators hospital, 45% of locally advanced pancreatic cancer patients treated with CCRT suffered from GI ulcers, and among them, 65% of the patients experienced the significant hemorrhage events. Although these GI toxicities, the studies for radioprotective agents were limited. Albis® is a newly developed drug comprised of ranitidine, bismuth and sucralfate. The investigators will investigate the radioprotective effect of Albis® for locally advanced pancreatic cancer patients treated with CCRT.

Prevention of Upper Gastrointestinal Hemorrhage Using Albis® in the Patients of Locally Advanced Pancreatic Cancer Who Underwent Concurrent Chemoradiotherapy

After 1 month after the chemoradiation, all the patients receive the esophagogastroduodenoscopy to detect the development of gastrointestinal ulcers. The proportion of patients with radiation-induced GI ulcers in each group will be investigated

Yonsei University

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Uterine Cervical Neoplasms

Endometrial Neoplasms

Urinary Bladder Neoplasms

Uterine Neoplasms

Genital Neoplasms, Female

Urogenital Neoplasms

Uterine Cervical Diseases

Uterine Diseases

Genital Diseases, Female

Genital Diseases

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urologic Neoplasms

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

No intervention: Questionnaires, food diaries and stool sample.

Caroline Henson, MBBS FRCP PhD

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.

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.

Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome

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

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

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.

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

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

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

Acceptability of recruitment process to patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Experience of the study process by patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Practicality and acceptability of obtaining stool samples for patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Rate of patient leaving the study before completing

Reason for patient leaving the study before completing

Acceptability of questionnaires and food diaries to patient cohort measured using internally generated non-validated questionnaire led by the research nurse

Proportion of patients who complete the study eg rate of attrition of patients and rate of missing data items

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

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

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Probiotics in Radiation-treated Gynecologic Cancer	NCT02351089	Gastrointestina... Gynecologic Can...	Capsules placeb... Capsules probio...	18 Years -	Probi AB
Prevention of Upper Gastrointestinal Hemorrhage Using Albis® in the Patients of Locally Advanced Pancreatic Cancer Who Underwent Concurrent Chemoradiotherapy	NCT02570529	Pancreatic Duct...	Albis® Placebo	20 Years - 80 Years	Yonsei University
Prevention of Upper Gastrointestinal Hemorrhage Using Albis® in the Patients of Locally Advanced Pancreatic Cancer Who Underwent Concurrent Chemoradiotherapy	NCT02570529	Pancreatic Duct...	Albis® Placebo	20 Years - 80 Years	Yonsei University
Probiotics in Radiation-treated Gynecologic Cancer	NCT02351089	Gastrointestina... Gynecologic Can...	Capsules placeb... Capsules probio...	18 Years -	Probi AB
Effect of Pelvic Radiotherapy on the Intestinal Microbiome and Metabolome	NCT04995809	Urinary Bladder... Uterine Cervica... Endometrial Neo...		18 Years -	The Christie NHS Foundation Trust
Prevention of Upper Gastrointestinal Hemorrhage Using Albis® in the Patients of Locally Advanced Pancreatic Cancer Who Underwent Concurrent Chemoradiotherapy	NCT02570529	Pancreatic Duct...	Albis® Placebo	20 Years - 80 Years	Yonsei University

Spots Global Cancer Trial Database for gastrointestinal toxicity