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

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

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).

Study Overview

• Status: Not yet recruiting
• Conditions: Clostridium Difficile Infection Recurrence
• Intervention / Treatment: Dietary supplement: Bacillus velezensis DSM 33864; Dietary supplement: Placebo

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Estimated): 104
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Victoria Oyedokun, PhD; Phone Number: +491723244702; Email: vtoy@novozymes.com
• Study Contact Backup: Name: Caterina Holz, PhD; Phone Number: +49 30921076554; Email: caho@novozymes.com

Study Locations

• United States
  • Michigan
    • Royal Oak, Michigan, United States, 48073
      • Beaumont Hospital
      • Contact: Matthew Sims, PhD
      • Contact: Maureen Cooney; Phone Number: 248-551-0099; Email: maureen.cooney@beaumont.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Males and females ≥ 18 years old
2. 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.
3. Able to provide signed and dated informed consent or assent
4. Able to provide blood and fecal specimens

Exclusion Criteria:

1. Current episode of CDI or delayed symptom resolution from previous reoccurrence (second episode), according to the physical exam and investigator assessment
2. Pregnancy or breastfeeding
3. Subjects presenting with active diarrhea (3 or more stools per 24-hour period) and within Bristol stool scale range of 5-7
4. 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)
5. Previous reaction, including anaphylaxis, to any substance in composition of the study product
6. Active, non-controlled intestinal disease such as Crohn's Disease, ulcerative colitis; celiac disease, or other chronic diarrheal illness
7. Patients with active Pancreatitis
8. Ostomized subjects, parenteral nutrition users
9. 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
10. 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);
11. Pregnant or lactating women or intending to become pregnant within 3 months ahead

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo control group; A placebo capsule containing microcrystalline cellulose will be taken orally, once a day, for 8 weeks.	Dietary supplement: Placebo; 1 microcrystalline cellulose-containing placebo capsule to be taken orally once a day with breakfast, for 8 weeks.
Experimental: Bacillus velezensis DSM 33864; 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; 1 probiotic capsule to be taken orally once a day, with breakfast, once a day for 8 weeks.; Other Names: Probiotic

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events	Incidence of adverse events from baseline to 12 weeks	12 weeks
Changes in hemoglobin concentration	Changes in hemoglobin concentration from baseline to 12 weeks determined by standard Full Blood Count (FBC) test	12 weeks
Changes in blood platelet levels	Changes in blood platelet levels from baseline to 12 weeks determined by standard Full Blood Count (FBC) test	12 weeks
Changes in blood C-reactive protein (CRP) levels	Changes in C-reactive levels from baseline to 12 weeks determined by standard blood CRP test	12 weeks
Changes in blood glucose levels	Changes in blood glucose from baseline to 12 weeks determined by standard blood chemistry panel test	12 weeks
Changes in blood urea nitrogen (BUN) levels	Changes in blood urea nitrogen levels from baseline to 12 weeks determined by standard blood chemistry panel test	12 weeks
Changes in blood creatinine levels	Changes in blood creatinine levels from baseline to 12 weeks determined by standard blood chemistry panel test	12 weeks
Changes in blood calcium levels	Changes in blood calcium levels from baseline to 12 weeks determined by standard blood chemistry panel test	12 weeks
Incidence of any diarrhea determined by the Bristol Stool Scale (score range 5-7)	Incidence of any diarrhea determined by the Bristol Stool Scale (score range 5-7)	12 weeks
Incidence of gastrointestinal pain or discomfort determined by GSRS questionnaire	Incidence of gastrointestinal pain or discomfort determined by GSRS questionnaire	12 weeks
Change in intestinal bile acid levels	Change in bile acids assessed from fecal samples by UPLC-MS	12 weeks
Change in intestinal short-chain fatty-acid levels	Change in short chain fatty acids assessed from fecal samples by GC-MS	12 weeks
Recovery rate of Bacillus velezensis assessed from fecal samples	Recovery rate of probiotic Bacillus velezensis DSM33864 in fecal samples, determined by qPCR method	12 weeks
Intestinal microbiome diversity including functional and resistome genes	Change in intestinal microbiome composition assessed from fecal samples using Deep Shotgun sequencing method	8 weeks

Collaborators and Investigators

• Sponsor: Novozymes A/S
• Collaborators: Estimates OY
• Investigators: Principal Investigator: Matthew Sims, PhD, Beaumont Hospital, Royal Oak. Michigan

Study record dates

Study Major Dates

• Study Start (Estimated): November 1, 2023
• Primary Completion (Estimated): November 1, 2024
• Study Completion (Estimated): December 1, 2024

Study Registration Dates

• First Submitted: August 9, 2022
• First Submitted That Met QC Criteria: October 31, 2022
• First Posted (Actual): November 4, 2022

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Dietary supplement; Probiotic; Gastrointestinal Microbiota; C. difficile
• Additional Relevant MeSH Terms: Pathologic Processes; Disease Attributes; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Infections; Communicable Diseases; Recurrence; Clostridium Infections
• Other Study ID Numbers: NZ-GHCD-2021-06

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No