This will be an adaptive design, randomised double-blind controlled clinical trial investigating oral exposure to NTCD spores in healthy volunteers, who are not colonised with C.difficile prior to the study and have not used antibiotics within one month prior to inclusion. A total of 50 volunteers will be included, divided over two consecutive intervention phases. The first phase will consist of 25 volunteers, randomised in three groups: group A (N=10) will receive 5 doses of 10E4 NTCD spores, group B (N=10) will receive 5 doses of 10E7 NTCD spores and group C (N=5) will receive 5 doses of placebo. Depending on the outcome of phase 1, the dose given in phase 2 will either be reduced (if colonisation frequency in phase 1 is high), or the doses will be preceded by vancomycin pre-treatment (if the colonisation frequency in phase 1 is low) according to predefined criteria. The second phase will also consist of 25 volunteers, randomized in 3 groups: group D (N=10), group E (N=10) and the control group F (N=5).~All volunteers in both phases will visit the trial center on the days of spores or placebo ingestion, with collection of feces for C.difficile and microbiota analysis before ingestion. During the four follow-up weeks volunteers will visit the trial center three times a week for fecal sample collection (for Cdiff and microbiota analysis), with weekly follow-up visit for AE collection and 2 times a safety blood tests. After three months there will be a final follow-up visit for AEs and fecal sample collection. Should a volunteer still be positive for C.difficile at the three month timepoint, the volunteer is asked to return for follow-up every one to two months for fecal sample collection until the sample is negative for C.difficile, up till a maximum of one year after the start of the trial. Because colonisation with NTCD is very common in the general population, NTCD colonisation will not be terminated with antibiotics. Rescue treatment for NTCD is available in case of unexpected adverse events.
This study will investigate experimental colonisation with non-toxigenic C.difficile (NTCD) in healthy volunteers. Main outcomes will be safety, tolerability, dose needed to obtain colonisation with NTCD and host microbiota factors associated with colonisation.