NCT06702345

Clostridioides Difficile Controlled Human Infection Model

Establishing a Clostridioides Difficile Controlled Human Infection Model

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 60 (estimated)
• Sponsor: Leiden University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

This study will investigate in healthy study subjects, the safety and tolerability of a controlled infection with Clostridioides difficile, a gut bacterium that can cause diarrhoea. It is also examined which dosing regimen (with or without antibiotic pretreatment) is required to induce mild symptoms (like diarrhoea) in the majority of study subjects and which microbiota and immunological factors influence this. To investigate this, healthy adult study subjects will be asked to ingest capsules (pills) containing the Clostridioides bacterium.

Detailed description

This will be a first in human, open-label, adaptive clinical trial investigating the oral exposure of toxigenic C. difficile in healthy volunteers. The trial will consist of at least one cohort (cohort A), with an option to escalate to a second (cohort B) and third cohort (cohort C) if needed. In every cohort volunteers will be exposed for 12 consecutive days (D0-D11) to once a day a capsule with 10\^4 CFU toxigenic C. difficile spores. Escalation will be done by adding antibiotic pretreatment (vancomycin in cohort B and clindamycin in cohort C) the five days before C. difficile exposure (D-6 - D-1). Escalation will be based upon safety first and secondly upon microbiological and clinical endpoints (ideally aiming for a 70% attack rate in both). In every cohort there will be first a pilot group of 5 volunteers, after which there is an option to include a confirmatory group of 15 more participants in the same cohort if the exposure is safe and the threshold for the microbiological and clinical endpoint is met. Immediately following the first ingestion of the C. difficile spores (day 0), volunteers will be closely and strictly monitored for adverse events (AEs) and vital signs in an outpatient setting. Until day 35, AEs, vital signs and stool samples for C. difficile toxin PCR/EIA, culture, and microbiota analysis will be collected every other day, safety laboratory measurements will be performed once in four days (starting from day 0). Immunology samples will be collected on day 0, 2, 20, 35 and 84. If a volunteer develops symptoms of CDI the volunteer needs to visit the research clinic the same day for a physical check-up, and collection of a blood and stool sample, and, if needed (antibiotic) treatment will be started according to standard of care. Any recurrent episode of a C. difficile infection will be treated with fecal microbiota transplantation (FMT). A final visit will take place after three months (day 84), with collection of feces and blood. If a volunteer is still C. difficile positive at this timepoint, they will be followed every three months until decolonisation is reached, up to a maximum of one year after the start of the trial. Decolonisation will be de-fined as having a negative molecular C. difficile test on at least two different timepoints.

Conditions

• C. Difficile
• C. Difficile Infection
• Controlled Human Infection

Interventions

Type	Name	Description
OTHER	encapsulated 10^4 CFU toxigenic. C. difficile spores	12 consecutive days of once a day a capsule with 10\^4 CFU toxigenic C. difficile spores.
DRUG	Vancomycin	oral vancomycin pretreatment, 4 times a day 250mg, given the five days before toxigenic C. difficile exposure.
DRUG	Clindamycin	oral clindamycin pretreatment, 3 times a day 600mg, given the five days before toxigenic C. difficile exposure

Timeline

• Start date: 2025-03-01
• Primary completion: 2026-07-01
• Completion: 2026-12-31
• First posted: 2024-11-22
• Last updated: 2024-11-22

Locations

1 site across 1 country: Netherlands