Bacillus Velezensis DSM 33864 for Reduction of the Risk of Recurrent Clostridioides Difficile Infections

Study Overview
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Brief Summary
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The purpose of this study is to determine whether a single strain capsulated probiotic, when used after standard C. difficile antibiotic therapy, is effective in reducing the risk of infection recurrence mediated by a decrease in colonization by toxigenic C. difficile. This study will include adults with a history of two episodes of C. difficile infection (CDI).

Detailed Description
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The goal of this multi-center randomized double-blinded placebo-controlled trial is to evaluate the tolerability and effect of a probiotic dietary supplement on the reduction of the risk of recurrent C. difficile infection in adults who have experienced two previous C. difficile infection episodes. The main aim of this study is to assess the effect of a probiotic dietary supplement on the colonization (cell counts) of C. difficile over time and also to assess the correlation between level of C. difficile colonization and recurrence of CDI. Approximately, 104 research subjects will be randomized into two arms and will use either one capsule daily of the probiotic supplement or placebo once daily with breakfast, for 8 weeks. All outcomes will be compared across the supplementation and placebo arm.

Official Title
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A Randomized, Double-blind, Placebo-controlled Clinical Trial to Evaluate the Tolerability and Effect of Bacillus Velezensis DSM 33864 on the Reduction of Risk of Recurrent Clostridioides Difficile Infection (rCDI) in Adults With a History of rCDI

Conditions
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Clostridium Difficile Infection Recurrence

Intervention / Treatment
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* Dietary Supplement: Bacillus velezensis DSM 33864
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females ≥ 18 years old Medical record documentation of second or subsequent recurrent CDI episode, and received standard-of-care oral antibiotic therapy completed no more than 5 days prior date of enrollment. Able to provide signed and dated informed consent or assent Able to provide blood and fecal specimens Exclusion Criteria: Current episode of CDI or delayed symptom resolution from previous reoccurrence (second episode), according to the physical exam and investigator assessment Pregnancy or breastfeeding Subjects presenting with active diarrhea (3 or more stools per 24-hour period) and within Bristol stool scale range of 5-7 Taking dietary supplement or therapeutic intervention which could significantly affect parameter(s) followed during the study (fibers, probiotics, prebiotics, symbiotic) according to the investigator or stopped in a too short period before the V1 visit (< 4 weeks) Previous reaction, including anaphylaxis, to any substance in composition of the study product Active, non-controlled intestinal disease such as Crohn's Disease, ulcerative colitis; celiac disease, or other chronic diarrheal illness Patients with active Pancreatitis Ostomized subjects, parenteral nutrition users Under immunosuppressive therapy or any health condition causing immunosuppression (including active hematological malignancies, acquired immune deficiency syndrome (AIDS), recent solid organ transplant (within 90 days),under treatment for rejection For women: Non menopausal with the same reliable contraception since at least 3 cycles before the beginning of the study and agreeing to keep it during the entire duration of the study or menopausal without or with hormone replacement therapy (estrogenic replacement therapy begun from less than 3 months excluded); Pregnant or lactating women or intending to become pregnant within 3 months ahead

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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Accepts Healthy Volunteers

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: Randomized, double-blind, placebo-controlled multicenter clinical trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Bacillus velezensis DSM 33864<br>This arm will receive a single strain probiotic capsule containing Bacillus velezensis DSM 33864. The probiotic will be taken orally, once a day, for 8 weeks. | Dietary Supplement: Bacillus velezensis DSM 33864<br>* 1 probiotic capsule to be taken orally once a day, with breakfast, once a day for 8 weeks.<br>* Other names: Probiotic;|
| Placebo Comparator: Placebo control group<br>A placebo capsule containing microcrystalline cellulose will be taken orally, once a day, for 8 weeks. | Dietary Supplement: Placebo<br>* 1 microcrystalline cellulose-containing placebo capsule to be taken orally once a day with breakfast, for 8 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C. difficile colonization | Change in colonization (counts) of toxigenic C. difficile from baseline to 8 weeks determined by quantitative PCR | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| C. difficile colonization | Change in colonization (counts) of toxigenic C. difficile determined by quantitative PCR | 4 weeks | 
| C.difficile colonization | Change in colonization (counts) of toxigenic C.difficile determined by quantitative PCR | 12 weeks | 
| Presence and levels of C. difficile toxin in fecal samples | Change in concentration of C. difficile Toxin A or B levels in fecal samples from baseline to week 4, week 8 and week 12 determined by enzyme immune assay method (EIA) | 12 weeks | 
| Quality of life assessment | Change in average health-related quality of life scores at baseline, week 8 and 12, determined by EQ-5D-5L questionnaire | 12 weeks | 
| Reduction of the risk of rCDI | Incidence of rCDI defined as an episode of diarrhea onset described by three or more unformed stools per 24 h as measured by the Bristol stool chart (types 5 to 7), and positive toxin assay result for C. difficile. | 8 weeks | 
| Reduction of the risk of rCDI | Incidence of rCDI defined as an episode of diarrhea onset described by three or more unformed stools per 24 h as measured by the Bristol stool chart (types 5 to 7), and positive toxin assay result for C. difficile. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Probiotic, Gastrointestinal Microbiota, C. difficile, Dietary supplement