Clostridioides Difficile Colonisation

NCT05693077 | Unknown Phase 1 DMC

• 1 other identifier: CloDiCo
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Clostridioides Difficile Infection

Keywords

Colonization

Outcome Measures

Primary Outcomes (2)

• Safety and tolerability of colonisation with non-toxigenic C.difficile

  Number and grade of related adverse events from day 1 to 28 after ingestion of NTCD spores.

  During the first month after ingestion of NTCD spores.

• To establish the effective protocol to obtain colonisation with non-toxigenic C. difficile in the majority of subjects.

  The number of volunteers successfully colonised with non-toxigenic C.difficile. Colonisation is defined as a positive PCR for C.difficile on stool or a positive culture for C.difficile on at least two timepoints between three days and two weeks after the last exposure day.

  During the first month after ingestion of NTCD spores.

Secondary Outcomes (1)

• To determine factors in the host microbiota associated with successful colonisation.

  3 months after ingestion of NTCD spores.

Other Outcomes (2)

• Determine changes in the host microbiota following colonisation.

  3 months after ingestion of NTCD spores.

• Investigate C. difficile in-vivo evolution.

  3 months after ingestion of NTCD spores.

Study Arms (9)

Group A (phase 1) (N=10)

EXPERIMENTAL

5 doses of 10E4 NTCD spores on day 0-4.

Biological: 10E4 NTCD spores

Group B (phase 1) (N=10)

EXPERIMENTAL

5 doses of 10E7 NTCD spores on day 0-4.

Biological: 10E7 NTCD spores

Group C (phase 1) (N=4)

PLACEBO COMPARATOR

5 doses of placebo on day 0-4.

Other: placebo

Group D (phase 2) (N=10)

EXPERIMENTAL

Based upon the colonisation results of phase 1, there are three dosing options for this group, one of the three options will be chosen, the chosen option number will be congruent for all three groups in phase 2: * Option 1: 3 doses of 10E4 NTCD spores on day 0-2. * Option 2: 3 doses of 10E7 NTCD spores on day 0-2. * Option 3: 1 day of vancomycin on day -7, followed by 5 doses of 10E4 NTCD spores on day 0-4.

Biological: 10E4 NTCD spores; Biological: 10E7 NTCD spores; Drug: Vancomycin Oral Capsule

Group E (phase 2) (N=10)

EXPERIMENTAL

Based upon the colonisation results of phase 1, there are three dosing options for this group, one of the three options will be chosen, the chosen option number will be congruent for all three groups in phase 2: * Option 1: 1 dose of 10E4 NTCD spores on day 0, and 2 doses of placebo on day 1-2. * Option 2: 1 dose of 10E7 NTCD spores on day 0, and 2 doses of placebo on day 1-2. * Option 3: 1 day vancomycin on day -7 followed by 5 doses of 10E7 NTCD spores on day 0-4.

Biological: 10E4 NTCD spores; Biological: 10E7 NTCD spores; Other: placebo; Drug: Vancomycin Oral Capsule

Group F (phase 2) (N=3 or 6)

PLACEBO COMPARATOR

Based upon the colonisation results of phase 1, there are three dosing options for this group, one of the three options will be chosen, the chosen option number will be congruent for all of the groups: * Option 1 (N=6): 3 doses of placebo on day 0-2. * Option 2 (N=6): 3 doses of placebo on day 0-2. * Option 3 (N=3): 1 day vancomycin on day -7, followed by 5 doses of placebo on day 0-4.

Other: placebo; Drug: Vancomycin Oral Capsule

Group G (phase 3) (N=10)

EXPERIMENTAL

Escalation to the third phase will only be done if option 3 is selected in phase 2. Based upon the colonisation results of phase 2, there are three dosing options for this group, one of the three options will be chosen, the chosen option number will be congruent for all of the groups in phase 3: * Option 1: 1 day vancomycin on day -7, followed by 3 doses of 10E4 NTCD spores on day 0-2. * Option 2: 1 day vancomycin on day -7, followed by 3 doses of 10E7 NTCD spores on day 0-2. * Option 3: 5 days of vancomycin on day -11 until day -7, followed by 5 doses of 10E4 NTCD spores on day 0-4.

Biological: 10E4 NTCD spores; Biological: 10E7 NTCD spores; Drug: Vancomycin Oral Capsule

Group H (phase 3) (N=10)

EXPERIMENTAL

Escalation to the third phase will only be done if option 3 is selected in phase 2. Based upon the colonisation results of phase 2, there are three dosing options for this group, one of the three options will be chosen, the chosen option number will be congruent for all of the groups in phase 3: * Option 1: 1 day of vancomycin on day -7, followed by 1 dose of 10E4 NTCD spores on day 0, and 2 doses of placebo on day 1-2. * Option 2: 1 day of vancomycin on day -7, followed by 1 dose of 10E7 NTCD spores on day 0 and 2 doses of placebo on day 1-2. * Option 3: 5 days of vancomycin on day -11 until day -7, followed by 5 doses of 10E7 NTCD spores on day 0-4.

Biological: 10E4 NTCD spores; Biological: 10E7 NTCD spores; Other: placebo; Drug: Vancomycin Oral Capsule

Group I (phase 3) (N=3)

PLACEBO COMPARATOR

Escalation to the third phase will only be done if option 3 is selected in phase 2. Based upon the colonisation results of phase 2, there are three dosing options for this group, one of the three options will be chosen, the chosen option number will be congruent for all of the groups in phase 3: * Option 1: 1 day of vancomycin on day -7, followed by 3 doses of placebo on day 0-2. * Option 2: 1 day of vancomycin on day -7, followed by 3 doses of placebo on day 0-2. * Option 3: 5 days of vancomycin on day -11 until day -7, followed by 5 doses of placebo on day 0-4.

Other: placebo; Drug: Vancomycin Oral Capsule

Interventions

10E4 NTCD spores BIOLOGICAL

in capsule for oral ingestion.

Group A (phase 1) (N=10); Group D (phase 2) (N=10); Group E (phase 2) (N=10); Group G (phase 3) (N=10); Group H (phase 3) (N=10)

10E7 NTCD spores BIOLOGICAL

in capsule for oral ingestion.

Group B (phase 1) (N=10); Group D (phase 2) (N=10); Group E (phase 2) (N=10); Group G (phase 3) (N=10); Group H (phase 3) (N=10)

placebo OTHER

in capsule for oral ingestion.

Group C (phase 1) (N=4); Group E (phase 2) (N=10); Group F (phase 2) (N=3 or 6); Group H (phase 3) (N=10); Group I (phase 3) (N=3)

Vancomycin Oral Capsule DRUG

4 times a day 250mg

Group D (phase 2) (N=10); Group E (phase 2) (N=10); Group F (phase 2) (N=3 or 6); Group G (phase 3) (N=10); Group H (phase 3) (N=10); Group I (phase 3) (N=3)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• In order to be eligible to participate in this study, a subject must meet all of the following criteria:
• Subject is aged ≥ 18 and ≤ 45 years and in good health.
• Subject has adequate understanding of the procedures of the study and is able and willing to abide strictly thereby.
• For female subjects: subject agrees to use adequate contraception and not to breastfeed for the duration of study.
• Subject has signed informed consent.

You may not qualify if:

• A potential subject who meets any of the following criteria will be excluded from participation in this study:
• 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.
• 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).
• The use of strong P-glycoprotein-inhibitors (like Ciclosporin, Ketoconazole, Erythromycin, Clarithromycin, Verapamil and Amiodaron).
• Known allergy to vancomycin, metronidazole or fidaxomicin.
• Known allergy to glycerol.
• Known immunodeficiency disorders.
• 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.
• Positive fecal PCR with Clostridiodes or SSYC (Salmonella, Shigella, Yersinia or Campylobacter spp.) at screening.
• 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.
• Being an employee or student of the Experimental bacteriology group or the controlled human infection center at LUMC.

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

RECRUITING

MeSH Terms

Conditions

Clostridium Infections

Interventions

Vancomycin

Condition Hierarchy (Ancestors)

Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Glycopeptides; Glycoconjugates; Carbohydrates; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Meta Roestenberg, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Meta Roestenberg, MD, PhD

CONTACT

+31715262102; M.Roestenberg@lumc.nl

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The trial is double-blind, placebo-controlled.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. dr.

Model Details: The trial consists of two or, if necessary, three consecutive intervention phases with each three parallel intervention arms. The first phase consists 24 volunteers, the second phase of 23 or 26 volunteers, and the optional third phase of another 23 volunteers. The volunteers will be divided over three intervention arms.

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 20, 2023
• Study Start: September 22, 2023
• Primary Completion: June 1, 2024
• Study Completion: June 1, 2025
• Last Updated: October 17, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)