Investigating non-toxigenic C. difficile colonization in healthy volunteers

Establishing Colonisation With Non-toxigenic Clostridioides Difficile in Healthy Volunteers

This study is testing if healthy people can safely be colonized with non-toxigenic C. difficile to see how different doses affect their gut health.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Ages: 18 Years to 45 Years
• Sex: All
• Sponsor: Leiden University Medical Center (Academic / other)
• Locations: 1 site (Leiden)
• Trial ID: NCT05693077 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to explore the safety and tolerability of colonization with non-toxigenic Clostridioides difficile (NTCD) in healthy volunteers. It employs a randomized double-blind controlled design with an adaptive dose approach, where participants will receive varying doses of NTCD spores or a placebo. The study will consist of multiple phases, with the first phase involving 24 volunteers divided into three groups based on the dose of NTCD spores administered. The outcomes will help determine the necessary dose for effective colonization and identify microbiota factors influencing susceptibility.

Who should consider this trial

Good fit: Ideal candidates for this study are healthy adults aged 18 to 45 who meet specific health criteria.

Not a fit: Patients with underlying health conditions or those who have used antibiotics recently may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to new strategies for preventing Clostridioides difficile infections by understanding colonization dynamics.

How similar studies have performed: While this approach is innovative, similar studies have shown promise in understanding microbiota interactions, though this specific method is relatively novel.

Eligibility criteria

Inclusion Criteria:

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

1. Subject is aged ≥ 18 and ≤ 45 years and in good health.
2. Subject has adequate understanding of the procedures of the study and is able and willing to abide strictly thereby.
3. For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
4. Subject has signed informed consent.

Exclusion Criteria:

A potential subject who meets any of the following criteria will be excluded from participation in this study:

1. Any physical or psychiatric illness or conditions that could threaten or compromise the health of the subject during the study, influence their ability to participate in the trial or interfere with the interpretation of the study results, as determined by the trial physician.
2. Use of antibiotics (or other microbiota influencing products) within one month prior to inclusion.
3. Known immunosuppressive condition, including infection with Human Immunodeficiency Virus (HIV), use of systemic corticosteroids or other immune modifying drugs (with exception of antihistamines and topical steroids).
4. Regular use (defined by more than once weekly) of proton-pump inhibitors or H2- blockers during one month prior to inclusion.
5. The use of strong P-glycoprotein-inhibitors (like Ciclosporin, Ketoconazole, Erythromycin, Clarithromycin, Verapamil and Amiodaron).
6. Known allergy to vancomycin, metronidazole or fidaxomicin.
7. Known allergy to glycerol.
8. Known immunodeficiency disorders.
9. Known gastro-intestinal disease including but not limited to inflammatory bowel diseases (Crohn's disease, Colitis Ulcerosa), recent gastro-intestinal surgery, constipation defined by bowel movements less than every second day.
10. Positive fecal PCR with Clostridiodes or SSYC (Salmonella, Shigella, Yersinia or Campylobacter spp.) at screening.
11. Any condition that would put household members at a greater risk for transmission e.g. no access or use of flush toilet, household members belonging to vulnerable populations such as persons who are immunocompromised, children younger than 2 years of age and elderly older than 70 years of age.
12. For women of child bearing potential: a positive urine pregnancy test before inclusion or lactating at screening / during the trial.
13. Being an employee or student of the Experimental bacteriology group or the controlled human infection center at LUMC.

Where this trial is running

Leiden

• Leiden University Medical Center — Leiden, Netherlands (Recruiting)

Study contacts

• Principal investigator: Meta Roestenberg, MD, PhD — Leiden University Medical Center
• Study coordinator: Meta Roestenberg, MD, PhD

Conditions Clostridioides Difficile Infection; Colonization