Clinical trial NCT06088940: The Chemo-Gut Probiotic Trial for Cancer Survivors
Official title: 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
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Cancer
Psychosocial Problem
Gastrointestinal Dysfunction
Keywords: Gut microbiome
Patient Reported Outcomes
Probiotics
Cancer survivor
Lead sponsor: University of Calgary
Sponsor class: OTHER
First posted: 2023-10-18
Enrollment: 66
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Male, female, and non-binary, any ethnicity
2. Aged 18 years or older
3. Diagnosed with hematological cancers (leukemia, Hodgkin's, and non-Hodgkin lymphoma), breast, osteosarcoma, Ewing's sarcoma, gynecological (cervical, endometrial), prostate, or testicular
4. Stages I - IV, including metastatic if stable and off treatment
5. Have received chemotherapy (with or without radiation, surgery, or hormone therapy)
6. Have completed primary cancer treatments
7. Within 5 years from their final cancer treatments, with emphasis placed on recruiting those within the first year post-treatment
8. Not currently pregnant or planning to become pregnant during the 12-week study
9. 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
10. Able to provide stool samples
11. Fluent in English, and have access to a computer, smartphone, or tablet with internet access to complete questionnaires
12. Provide written informed consent

Exclusion Criteria:

1. Diagnosis of central nervous system tumor, or colorectal cancer
2. Taken antibiotics and/or daily probiotic (including probiotic yogurt) within the 1 month prior to study participation
3. Currently or previously receiving immunotherapy
4. Diagnosed with irritable bowel syndrome or inflammatory bowel disease prior to being diagnosed with cancer
5. Diagnosed with a developmental/cognitive delay prior to cancer (e.g. autism spectrum disorder, downs syndrome)
6. Pregnancy

Primary outcomes:
measure: Effects of probiotic on abdominal pain
timeFrame: 12 weeks
measure: Effects of probiotic on depression symptoms
timeFrame: 12 weeks
Secondary outcomes:
measure: Effects of probiotic on Gas/Bloating symptoms
timeFrame: 12 weeks
measure: Effects of probiotic on Diarrhea symptoms
timeFrame: 12 weeks
measure: Effects of probiotic on Constipation symptoms
timeFrame: 12 weeks
measure: Effects of probiotic on anxiety symptoms
timeFrame: 12 weeks
measure: Effects of probiotic on Fatigue symptoms
timeFrame: 12 weeks
measure: Effects of probiotic on cognitive function
timeFrame: 12 weeks
measure: Effects of probiotic on global health symptoms
timeFrame: 12 weeks
measure: Probiotic effects on gut microbiota alpha diversity composition
timeFrame: 12 weeks
measure: Probiotic effects on gut microbiota beta diversity composition
timeFrame: 12 weeks
measure: Probiotic effects on gut microbiota differential taxonomic abundance
timeFrame: 12 weeks
Other outcomes:
measure: Relationships between bacterial taxa and symptoms
timeFrame: 12 weeks
Locations:
Study officials:
affiliation: University of Calgary Cumming School of Medicine
name: Julie M Deleemans, PhD
role: STUDY_DIRECTOR
References:
citation: Deleemans JM, Chleilat F, Reimer RA, Henning JW, Baydoun M, Piedalue KA, McLennan A, Carlson LE. The chemo-gut study: investigating the long-term effects of chemotherapy on gut microbiota, metabolic, immune, psychological and cognitive parameters in young adult Cancer survivors; study protocol. BMC Cancer. 2019 Dec 23;19(1):1243. doi: 10.1186/s12885-019-6473-8.
citation: Deleemans JM, Toivonen K, Reimer RA, Carlson LE. The Chemo-Gut Study: A Cross-Sectional Survey Exploring Physical, Mental, and Gastrointestinal Health Outcomes in Cancer Survivors. Glob Adv Health Med. 2022 Dec 21;11:2164957X221145940. doi: 10.1177/2164957X221145940. eCollection 2022.
citation: Deleemans JM, Gajtani Z, Baydoun M, Reimer RA, Piedalue KA, Carlson LE. The Use of Prebiotic and Probiotic Interventions for Treating Gastrointestinal and Psychosocial Health Symptoms in Cancer Patients and Survivors: A Systematic Review. Integr Cancer Ther. 2021 Jan-Dec;20:15347354211061733. doi: 10.1177/15347354211061733.