Clostridium Difficile Infection Recurrence
Conditions
Keywords
Probiotic, Gastrointestinal Microbiota, C. difficile, Dietary supplement
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.
Interventions
DIETARY_SUPPLEMENTBacillus velezensis DSM 33864
1 probiotic capsule to be taken orally once a day, with breakfast, once a day for 8 weeks.
DIETARY_SUPPLEMENTPlacebo
1 microcrystalline cellulose-containing placebo capsule to be taken orally once a day with breakfast, for 8 weeks.
Sponsors
Estimates OY
Novozymes A/S
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomized, double-blind, placebo-controlled multicenter clinical trial
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| C. difficile colonization | 8 weeks | Change in colonization (counts) of toxigenic C. difficile from baseline to 8 weeks determined by quantitative PCR |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| C. difficile colonization | 4 weeks | Change in colonization (counts) of toxigenic C. difficile determined by quantitative PCR |
| C.difficile colonization | 12 weeks | Change in colonization (counts) of toxigenic C.difficile determined by quantitative PCR |
| Presence and levels of C. difficile toxin in fecal samples | 12 weeks | 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 | 12 weeks | 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 | 8 weeks | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in blood glucose levels | 12 weeks | Changes in blood glucose from baseline to 12 weeks determined by standard blood chemistry panel test |
| Changes in blood calcium levels | 12 weeks | Changes in blood calcium levels from baseline to 12 weeks determined by standard blood chemistry panel test |
| Incidence of any diarrhea determined by the Bristol Stool Scale (score range 5-7) | 12 weeks | Incidence of any diarrhea determined by the Bristol Stool Scale (score range 5-7) |
| Incidence of gastrointestinal pain or discomfort determined by GSRS questionnaire | 12 weeks | Incidence of gastrointestinal pain or discomfort determined by GSRS questionnaire |
| Changes in blood urea nitrogen (BUN) levels | 12 weeks | Changes in blood urea nitrogen levels from baseline to 12 weeks determined by standard blood chemistry panel test |
| Change in intestinal bile acid levels | 12 weeks | Change in bile acids assessed from fecal samples by UPLC-MS |
| Change in intestinal short-chain fatty-acid levels | 12 weeks | Change in short chain fatty acids assessed from fecal samples by GC-MS |
| Recovery rate of Bacillus velezensis assessed from fecal samples | 12 weeks | Recovery rate of probiotic Bacillus velezensis DSM33864 in fecal samples, determined by qPCR method |
| Intestinal microbiome diversity including functional and resistome genes | 8 weeks | Change in intestinal microbiome composition assessed from fecal samples using Deep Shotgun sequencing method |
| Changes in blood creatinine levels | 12 weeks | Changes in blood creatinine levels from baseline to 12 weeks determined by standard blood chemistry panel test |
| Incidence of adverse events | 12 weeks | Incidence of adverse events from baseline to 12 weeks |
| Changes in hemoglobin concentration | 12 weeks | Changes in hemoglobin concentration from baseline to 12 weeks determined by standard Full Blood Count (FBC) test |
| Changes in blood platelet levels | 12 weeks | Changes in blood platelet levels from baseline to 12 weeks determined by standard Full Blood Count (FBC) test |
| Changes in blood C-reactive protein (CRP) levels | 12 weeks | Changes in C-reactive levels from baseline to 12 weeks determined by standard blood CRP test |
Countries
United States
Outcome results
None listed