Clinical trial NCT05606159: 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
Overall status: WITHDRAWN
Phase: NA
Conditions: Clostridium Difficile Infection Recurrence
Keywords: Probiotic
Gastrointestinal Microbiota
C. difficile
Dietary supplement
Lead sponsor: Novozymes A/S
Sponsor class: INDUSTRY
Collaborators: name: Estimates OY
First posted: 2022-11-04
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, double-blind, placebo-controlled multicenter clinical trial
Primary purpose: SUPPORTIVE_CARE

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.

Eligibility criteria: 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

Primary outcomes:
measure: C. difficile colonization
timeFrame: 8 weeks
Secondary outcomes:
measure: C. difficile colonization
timeFrame: 4 weeks
measure: C.difficile colonization
timeFrame: 12 weeks
measure: Presence and levels of C. difficile toxin in fecal samples
timeFrame: 12 weeks
measure: Quality of life assessment
timeFrame: 12 weeks
measure: Reduction of the risk of rCDI
timeFrame: 8 weeks
measure: Reduction of the risk of rCDI
timeFrame: 4 weeks
Other outcomes:
measure: Incidence of adverse events
timeFrame: 12 weeks
measure: Changes in hemoglobin concentration
timeFrame: 12 weeks
measure: Changes in blood platelet levels
timeFrame: 12 weeks
measure: Changes in blood C-reactive protein (CRP) levels
timeFrame: 12 weeks
measure: Changes in blood glucose levels
timeFrame: 12 weeks
measure: Changes in blood urea nitrogen (BUN) levels
timeFrame: 12 weeks
measure: Changes in blood creatinine levels
timeFrame: 12 weeks
measure: Changes in blood calcium levels
timeFrame: 12 weeks
measure: Incidence of any diarrhea determined by the Bristol Stool Scale (score range 5-7)
timeFrame: 12 weeks
measure: Incidence of gastrointestinal pain or discomfort determined by GSRS questionnaire
timeFrame: 12 weeks
measure: Intestinal microbiome diversity including functional and resistome genes
timeFrame: 8 weeks
measure: Change in intestinal bile acid levels
timeFrame: 12 weeks
measure: Change in intestinal short-chain fatty-acid levels
timeFrame: 12 weeks
measure: Recovery rate of Bacillus velezensis assessed from fecal samples
timeFrame: 12 weeks
Locations:
city: Royal Oak
country: United States
facility: Beaumont Hospital
state: Michigan
Study officials:
affiliation: Beaumont Hospital, Royal Oak. Michigan
name: Matthew Sims, PhD
role: PRINCIPAL_INVESTIGATOR
References: