NCT05693077

Clostridioides Difficile Colonisation

Establishing Colonisation With Non-toxigenic Clostridioides Difficile in Healthy Volunteers

• Status: Unknown
• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: Leiden University Medical Center · Academic / Other
• Sex: All
• Age: 18 Years – 45 Years
• Healthy volunteers: Accepted

Summary

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 to ultimately determine host microbiota factors associated with susceptibility to colonisation.

Detailed description

This will be an adaptive dose design, randomized double-blind controlled clinical trial investigating oral exposure to NTCD spores in healthy volunteers. The trial will consist of two or, if necessary, three different consecutive intervention phases. The second and third phase are dependent on results of the preliminary phases. In every phase one cohort volunteers will be randomized to different dose levels of NTCD spores or placebo. 50 to 70 healthy volunteers will be included, of which in total 10 volunteers will be exposed to placebo. The first phase will consist of 24 volunteers, randomized 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=4) 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 \>60%), or the doses will be preceded by vancomycin pre-treatment (if the colonisation frequency in phase 1 is \<60%) according to predefined criteria. There are three dosing options for phase 2: for the first two options (reduced doses of NTCD) 26 volunteers will be divided over 3 groups group D (N=10), group E (N=10) and the control group F (N=6), for the third option (vancomycin pre-treatment) 23 volunteers will be divided over 3 groups; group D (N=10), group E (N=10) and the control group F (N=3). For the dosing schedules of the three options op the second phase please refer to the section below 'Arms and Interventions'. Escalation to the third phase will only be done if option 3 is selected in phase 2.Depending on the outcome of phase 2, the dose given in phase 3 will either be reduced (if colonisation frequency in phase 2 is \>60%) or the vancomycin pre-treatment will be extended to five days (if the colonisation frequency in phase 2 is \<60%) according to predefined criteria. 23 volunteers will be divided over 3 groups: group G (N=10), group H (N=10) and the control group I (N=3). For dosing schedules of the three options of the third phase please refer to the section below 'Arms and Interventions'. All volunteers in all phases will visit the trial center on the days of spores or placebo ingestion (and if needed also on the first day of vancomycin 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. Antibiotic rescue treatment (or in case of persistent disturbances to the host microbiota, a fecal microbiota transplantation) for NTCD is available in case of unexpected adverse events.

Conditions

• Clostridioides Difficile Infection

Interventions

Type	Name	Description
BIOLOGICAL	10E4 NTCD spores	in capsule for oral ingestion.
BIOLOGICAL	10E7 NTCD spores	in capsule for oral ingestion.
OTHER	placebo	in capsule for oral ingestion.
DRUG	Vancomycin Oral Capsule	4 times a day 250mg

Timeline

• Start date: 2023-09-22
• Primary completion: 2024-06-01
• Completion: 2025-06-01
• First posted: 2023-01-20
• Last updated: 2023-10-17

Locations

1 site across 1 country: Netherlands