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

Primary Purpose

Clostridium Difficile Infection Recurrence

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Bacillus velezensis DSM 33864
Placebo
Sponsored by
Novozymes A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Clostridium Difficile Infection Recurrence focused on measuring Probiotic, Gastrointestinal Microbiota, C. difficile, Dietary supplement

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

  • Beaumont Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Bacillus velezensis DSM 33864

Placebo control group

Arm Description

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.

A placebo capsule containing microcrystalline cellulose will be taken orally, once a day, for 8 weeks.

Outcomes

Primary Outcome Measures

C. difficile colonization
Change in colonization (counts) of toxigenic C. difficile from baseline to 8 weeks determined by quantitative PCR

Secondary Outcome Measures

C. difficile colonization
Change in colonization (counts) of toxigenic C. difficile determined by quantitative PCR
C.difficile colonization
Change in colonization (counts) of toxigenic C.difficile determined by quantitative PCR
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)
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
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.
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.

Full Information

First Posted
August 9, 2022
Last Updated
October 2, 2023
Sponsor
Novozymes A/S
Collaborators
Estimates OY
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1. Study Identification

Unique Protocol Identification Number
NCT05606159
Brief Title
Bacillus Velezensis DSM 33864 for Reduction of the Risk of Recurrent Clostridioides Difficile Infections
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
November 2023 (Anticipated)
Primary Completion Date
November 2024 (Anticipated)
Study Completion Date
December 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novozymes A/S
Collaborators
Estimates OY

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Clostridium Difficile Infection Recurrence
Keywords
Probiotic, Gastrointestinal Microbiota, C. difficile, Dietary supplement

7. Study Design

Primary Purpose
Supportive Care
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Randomized, double-blind, placebo-controlled multicenter clinical trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
104 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Bacillus velezensis DSM 33864
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo control group
Arm Type
Placebo Comparator
Arm Description
A placebo capsule containing microcrystalline cellulose will be taken orally, once a day, for 8 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Bacillus velezensis DSM 33864
Other Intervention Name(s)
Probiotic
Intervention Description
1 probiotic capsule to be taken orally once a day, with breakfast, once a day for 8 weeks.
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
1 microcrystalline cellulose-containing placebo capsule to be taken orally once a day with breakfast, for 8 weeks.
Primary Outcome Measure Information:
Title
C. difficile colonization
Description
Change in colonization (counts) of toxigenic C. difficile from baseline to 8 weeks determined by quantitative PCR
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
C. difficile colonization
Description
Change in colonization (counts) of toxigenic C. difficile determined by quantitative PCR
Time Frame
4 weeks
Title
C.difficile colonization
Description
Change in colonization (counts) of toxigenic C.difficile determined by quantitative PCR
Time Frame
12 weeks
Title
Presence and levels of C. difficile toxin in fecal samples
Description
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)
Time Frame
12 weeks
Title
Quality of life assessment
Description
Change in average health-related quality of life scores at baseline, week 8 and 12, determined by EQ-5D-5L questionnaire
Time Frame
12 weeks
Title
Reduction of the risk of rCDI
Description
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.
Time Frame
8 weeks
Title
Reduction of the risk of rCDI
Description
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.
Time Frame
4 weeks
Other Pre-specified Outcome Measures:
Title
Incidence of adverse events
Description
Incidence of adverse events from baseline to 12 weeks
Time Frame
12 weeks
Title
Changes in hemoglobin concentration
Description
Changes in hemoglobin concentration from baseline to 12 weeks determined by standard Full Blood Count (FBC) test
Time Frame
12 weeks
Title
Changes in blood platelet levels
Description
Changes in blood platelet levels from baseline to 12 weeks determined by standard Full Blood Count (FBC) test
Time Frame
12 weeks
Title
Changes in blood C-reactive protein (CRP) levels
Description
Changes in C-reactive levels from baseline to 12 weeks determined by standard blood CRP test
Time Frame
12 weeks
Title
Changes in blood glucose levels
Description
Changes in blood glucose from baseline to 12 weeks determined by standard blood chemistry panel test
Time Frame
12 weeks
Title
Changes in blood urea nitrogen (BUN) levels
Description
Changes in blood urea nitrogen levels from baseline to 12 weeks determined by standard blood chemistry panel test
Time Frame
12 weeks
Title
Changes in blood creatinine levels
Description
Changes in blood creatinine levels from baseline to 12 weeks determined by standard blood chemistry panel test
Time Frame
12 weeks
Title
Changes in blood calcium levels
Description
Changes in blood calcium levels from baseline to 12 weeks determined by standard blood chemistry panel test
Time Frame
12 weeks
Title
Incidence of any diarrhea determined by the Bristol Stool Scale (score range 5-7)
Description
Incidence of any diarrhea determined by the Bristol Stool Scale (score range 5-7)
Time Frame
12 weeks
Title
Incidence of gastrointestinal pain or discomfort determined by GSRS questionnaire
Description
Incidence of gastrointestinal pain or discomfort determined by GSRS questionnaire
Time Frame
12 weeks
Title
Intestinal microbiome diversity including functional and resistome genes
Description
Change in intestinal microbiome composition assessed from fecal samples using Deep Shotgun sequencing method
Time Frame
8 weeks
Title
Change in intestinal bile acid levels
Description
Change in bile acids assessed from fecal samples by UPLC-MS
Time Frame
12 weeks
Title
Change in intestinal short-chain fatty-acid levels
Description
Change in short chain fatty acids assessed from fecal samples by GC-MS
Time Frame
12 weeks
Title
Recovery rate of Bacillus velezensis assessed from fecal samples
Description
Recovery rate of probiotic Bacillus velezensis DSM33864 in fecal samples, determined by qPCR method
Time Frame
12 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Victoria Oyedokun, PhD
Phone
+491723244702
Email
vtoy@novozymes.com
First Name & Middle Initial & Last Name or Official Title & Degree
Caterina Holz, PhD
Phone
+49 30921076554
Email
caho@novozymes.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Sims, PhD
Organizational Affiliation
Beaumont Hospital, Royal Oak. Michigan
Official's Role
Principal Investigator
Facility Information:
Facility Name
Beaumont Hospital
City
Royal Oak
State/Province
Michigan
ZIP/Postal Code
48073
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Sims, PhD
First Name & Middle Initial & Last Name & Degree
Maureen Cooney
Phone
248-551-0099
Email
maureen.cooney@beaumont.org

12. IPD Sharing Statement

Plan to Share IPD
No

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

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