The Chemo-Gut Probiotic Trial for Cancer Survivors

Study Overview
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Brief Summary
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Purpose: The goal of this clinical trial is to determine whether probiotics can reduce gastrointestinal and psychosocial symptoms in post-treatment cancer survivors by impacting the gut microbiome. Objectives: The main questions the investigators aim to answer are: Does taking the probiotic reduce gastrointestinal (e.g. belly pain) and psychosocial (e.g. depressive symptoms, fatigue) symptoms, and impact the gut microbiome? What relationships exist between gut bacteria, gastrointestinal, and psychosocial symptoms? Methods: The study team will investigate this by giving a group of adult post-treatment cancer survivors either a probiotic capsule (intervention) or placebo capsule (control) over 12 weeks. Investigators will then analyze the bacterial diversity in participants' stool samples before and after these 12 weeks to see how the bacterial composition changed due to the treatment. Surveys will be used to ask participants questions about their physical and mental health, including specific gastrointestinal and psychosocial symptoms. Implications: Cancer recovery is tough enough, and to minimize treatment-related long-term effects through a simple probiotic capsule would immensely improve the well-being and health of survivors.

Detailed Description
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Background: Survivors of cancer experience chronic gastrointestinal (GI) and psychosocial health symptoms, and reduced gut microbial diversity. This may compromise survivors' long-term health and overall wellbeing. No studies have investigated probiotics for managing both GI and psychosocial symptoms together, or the composition of the gut microbiota in post-treatment cancer survivors. Aims: To investigate the effects of a probiotic vs. placebo on (i) abdominal pain and depressive symptoms (primary outcomes); (ii) (a) GI (i.e. gas/bloating, diarrhea, constipation) and psychosocial (i.e. anxiety, cognitive function, fatigue) symptoms, and general health; and (b) gut microbiota composition; (iii) relationships between bacteria, GI and psychosocial symptoms. Methods: This double-blinded, placebo-controlled, 2-arm, randomized trial will recruit N=66 participants allocated to the probiotic or placebo group for a 12-week trial. Adult survivors diagnosed with a solid tumour or blood cancer who have completed chemotherapy within the last 5 years, and show elevated GI or psychosocial symptoms will be included. The probiotic capsule contains Lactobacillus and Bifidobacterium strains, ingested orally once daily. Stool samples will be collected at baseline and week-12 and analyzed using GA-Map dysbiosis test and 16S rRNA gene sequencing. GI and psychosocial surveys will be completed at baseline, weeks 6 and 12. Descriptive statistics, frequencies, paired samples t-tests, linear mixed models, and Spearman's correlations analyses will be used. Implications: This study explores a novel, microbiota-based treatment for chronic GI and psychosocial symptoms in cancer survivors. These findings and commitment to patient-centred knowledge translation via creating patient materials (e.g. infographics, personal results summary) will enable patients to make informed decisions about their health.

Official Title
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The Chemo-Gut Trial: A Double-blind Randomized Controlled Trial Investigating the Effects of a Multi-strain Probiotic on Gut Microbiota, Gastrointestinal Symptoms, and Psychosocial Health in Cancer Survivors

Conditions
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Cancer, Psychosocial Problem, Gastrointestinal Dysfunction

Intervention / Treatment
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* Dietary Supplement: Multistrain Probiotic
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male, female, and non-binary, any ethnicity Aged 18 years or older Diagnosed with hematological cancers (leukemia, Hodgkin's, and non-Hodgkin lymphoma), breast, osteosarcoma, Ewing's sarcoma, gynecological (cervical, endometrial), prostate, or testicular Stages I - IV, including metastatic if stable and off treatment Have received chemotherapy (with or without radiation, surgery, or hormone therapy) Have completed primary cancer treatments Within 5 years from their final cancer treatments, with emphasis placed on recruiting those within the first year post-treatment Not currently pregnant or planning to become pregnant during the 12-week study Evidence of clinically elevated levels (i.e. a score of 56 or higher) of GI and/or comorbid psychosocial symptoms as determined using PROMIS short forms for abdominal pain, gas/bloating, and general mental and physical health Able to provide stool samples Fluent in English, and have access to a computer, smartphone, or tablet with internet access to complete questionnaires Provide written informed consent Exclusion Criteria: Diagnosis of central nervous system tumor, or colorectal cancer Taken antibiotics and/or daily probiotic (including probiotic yogurt) within the 1 month prior to study participation Currently or previously receiving immunotherapy Diagnosed with irritable bowel syndrome or inflammatory bowel disease prior to being diagnosed with cancer Diagnosed with a developmental/cognitive delay prior to cancer (e.g. autism spectrum disorder, downs syndrome) Pregnancy

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Theoretical Framework: This line of research follows the NIH ORBIT model for intervention development. Briefly, the ORBIT model provides a generic, systematic framework that emphasizes using a set of studies to form a chain of evidence that ultimately indicates readiness for an efficacy trial. Study Design. Consistent with the National Institutes for Health (NIH) clinical trial phases for drug development, this study will fit into phase II, where investigators are focused on examining treatment effectiveness. A placebo-controlled randomized double-blinded study design is the gold standard for intervention research involving medications or natural health products, such as probiotics.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Probiotic Group (Group 1: Experimental intervention)<br>Participants will be given a 12-week supply of the probiotic supplement and asked to take 1 capsule daily by mouth at the same time as their first meal of the day. | Dietary Supplement: Multistrain Probiotic<br>* The probiotic capsule contains Lactobacillus and Bifidobacterium strains, ingested orally once daily.<br>|
| Placebo Comparator: Placebo Group (Group 2: Control condition)<br>Participants will be given a 12-week supply of the placebo capsules and asked to take 1 capsule daily by mouth at the same time as their first meal of the day. | Other: Placebo<br>* Placebo is composed of maltodextrin, that is an identically formulated and packaged inactive substance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of probiotic on abdominal pain | Endpoint: Clinically meaningful effects will be defined as reductions of 3 points or more from baseline scores of abdominal pain symptoms on PROMIS measures. Measure: PROMIS Belly Pain - Scale v1.0, 5a; Scores range from 20 to 80. Higher scores >60 indicate more symptoms. | 12 weeks | 
| Effects of probiotic on depression symptoms | Endpoint: Clinically meaningful effects will be defined as reductions of 3 points or more from baseline scores of depression on PROMIS measures. Measure: PROMIS Ca Item Bank v1.0 - Emotional Distress - Depression questionnaire; Scores range from 20 to 80. Higher scores >60 indicate more symptoms. | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effects of probiotic on Gas/Bloating symptoms | Endpoint: Effects of probiotics on: Gas/bloating Measure: PROMIS Gas and Bloating - Scale v1.1 13a | 12 weeks | 
| Effects of probiotic on Diarrhea symptoms | Endpoint: Effects of probiotics on: Diarrhea Measure: PROMIS Diarrhea - Scale v1.0, 6a | 12 weeks | 
| Effects of probiotic on Constipation symptoms | Endpoint: Effects of probiotics on: Constipation Measure: PROMIS constipation - Scale v1.0, 9a | 12 weeks | 
| Effects of probiotic on anxiety symptoms | PROMIS Anxiety: v1.0 - Anxiety - Short Form 8a; Scores range from 20 to 80. Higher scores >60 indicate more symptoms. | 12 weeks | 
| Effects of probiotic on Fatigue symptoms | PROMIS v1.0 - Fatigue - Short Form 8a. Scores range from 20 to 80. Higher scores >60 indicate more symptoms. | 12 weeks | 
| Effects of probiotic on cognitive function | Measure: PROMIS v2.0 - Cognitive Function; Scores range from 80 (high function) to 20 (severe dysfunction). | 12 weeks | 
| Effects of probiotic on global health symptoms | Measure: PROMIS Global Health - Scale v1.2; Scores range from 80 (Excellent health) to 20 (Poor health). | 12 weeks | 
| Probiotic effects on gut microbiota alpha diversity composition | Measure: Chao1, Shannon, and Simpson index for statistically significant differences in alpha diversity between groups | 12 weeks | 
| Probiotic effects on gut microbiota beta diversity composition | Measure: Bray-Curtis index for statistically significant differences in beta diversity between groups | 12 weeks | 
| Probiotic effects on gut microbiota differential taxonomic abundance | Measure: statistically significant differences in differential taxonomic abundance (ASV's) between groups | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gut microbiome, Patient Reported Outcomes, Probiotics, Cancer survivor