C. DifficileCloDiCHINCT06702345
Clostridioides Difficile Controlled Human Infection Model
A study testing encapsulated 10^4 CFU toxigenic. C. difficile spores, Vancomycin and Clindamycin in people with C. Difficile and C. Difficile Infection, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- C. Difficile, C. Difficile Infection, Controlled Human Infection
- What is being tested?
- encapsulated 10^4 CFU toxigenic. C. difficile spores, Vancomycin and Clindamycin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteNetherlands
- Study dates
- 1 Mar 2025to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Subject is aged ≥18 and ≤45 years and in good health;
- Body mass index (BMI) ≥18.0 and <30.0 kg/m2;
- Subject has adequate understanding of the procedures of the study and is able and willing to abide strictly thereby;
- Subject is able to communicate well with the investigator, is willing to follow hygienic measures and instructions;
- For women of childbearing potential: subject agrees to use adequate contra-ception (see Appendix D for the different adequate contraception methods for this study) and not to breastfeed for the duration of the study;
- Subject has signed informed consent.
Who cannot join
- Any physical or psychiatric illness or conditions that could threaten or com-promise the health of the subject during the study, influence their ability to par-ticipate in the trial or interfere with the interpretation of the study results, as de-termined by the trial physician;
- Use of systemic (IV or oral) antibiotics within three months prior to screening; other microbiota influencing medication (that could influence the trial, based on the Investigator's opinion) within 1 month prior to screening visit. Prior use of topical antibiotics is permitted if there is no clinically relevant systemic ex-pected following assessment of the trial physician and are expected to be dis-continued during the start of the first study activity.
- Has had a recent hospitalization (e.g. 3 months prior to screening) and/or has someone in immediate social circle who is frequently hospitalized (≥3 times in a 12-month period) or frequently exposed to hospital settings (≥ one time a month, e.g. dialysis units);
- Regular use (defined by more than once weekly) of proton-pump inhibitors or H2-blockers during one month prior to screening;
- Chronic use of immunosuppressive drugs, e.g. systemic corticosteroids or other immune modifying drugs (with exception of oral anti-histamines and top-ical/inhaled corticosteroids);
- Positive HIV, Hepatitis B or C screening tests;
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- Known immunodeficiency disorders;
- The use of strong P-glycoprotein-inhibitors (like ciclosporin, ketoconazole, erythromycin, clarithromycin, verapamil and amiodaron) during the trial;
- Known allergy to vancomycin, clindamycin, fidaxomicin (and macrolides), or metronidazole;
- Any known significant allergy against the excipients of C. difficile inoculum or inability to swallow capsules;
- Known gastro-intestinal disease including but not limited to inflammatory bow-el diseases (Crohn's disease, Colitis ulcerosa), a history of bowel resection or any other gastro-intestinal surgery which has significantly changed the ana-tomical structure or physiological function of the gastro-intestinal tract, bile ac-id secretion abnormalities, constipation defined by bowel movements less than every second day or chronic use of laxatives;
- Positive fecal culture or PCR with toxigenic or non-toxigenic Clostridioides spp. or SSYC (Salmonella spp., Shigella spp., Yersinia spp. or Campylobac-ter spp.) at screening, or recent (<14 days) history of diarrhoea (i.e. as ≥3 loose stools (Bristol stool scale 6-7) in 24 hours);
- Any condition that would put household members or close contacts at a great-er risk for transmission e.g. no access or use of flush toilet;
- Individuals living, working or having close contact with people who belong to vulnerable populations such as hospitalized patients, pregnant women, im-mune compromised individuals, children younger than 2 years, residents of nursing homes, elderly older than 70 years of age, or any person with a medi-cal condition at risk of developing severe CDI.
- Individuals working in food preparation;
- Individuals having close contact with healthcare personal/individuals working in food preparation;
- For women of childbearing potential; a positive serological pregnancy test at screening or lactating at screening/ during the trial;
- History of drug or alcohol abuse interfering with normal social functioning in the period of one year prior to study onset, positive urine toxicology test for il-licit drug use at screening;
- Receipt of another investigational agent within 90 days prior or 60 days after C. difficile ingestion;
- Any condition or situation that could influence the independent consent of par-ticipant (e.g. being a direct colleague or family member of study personnel).
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Netherlands1 site
Leiden University Medical Center
Leiden, South Holland, 2333ZA
Drs. Annefleur Hensen, 0031620942061, a.d.o.hensen@lumc.nl
About this study
Official title: Establishing a Clostridioides Difficile Controlled Human Infection Model
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.
Read the 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.
- Being tested
- encapsulated 10^4 CFU toxigenic. C. difficile spores, Vancomycin, Clindamycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
encapsulated 10^4 CFU toxigenic. C. difficile sporesOther
12 consecutive days of once a day a capsule with 10^4 CFU toxigenic C. difficile spores.
VancomycinDrug
oral vancomycin pretreatment, 4 times a day 250mg, given the five days before toxigenic C. difficile exposure.
ClindamycinDrug
oral clindamycin pretreatment, 3 times a day 600mg, given the five days before toxigenic C. difficile exposure
| Study group | Role | What they receive |
|---|---|---|
| Cohort A (TCD spores only) | Experimental | Volunteers in cohort A will be exposed to a once a day capsule with 10^4 CFU TCD spores for 12 days. First, a pilot group of 5 volunteers will be exposed to flag safety signals. If in this pilot group TCD exposure is well tolerated and less than 70% of the volunteers (< 4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, the trial will escalate to the second cohort, cohort B. If, however, in the pilot group TCD exposure is well tolerated and at least 70% of the volunteers (≥4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, a confirmatory group of another 15 volunteers will be included in cohort A (total 20 volunteers). If in this total of 20 volunteers sat least 70% (≥ 14 out of 20 volunteers) reaches a clinical AND microbiological endpoint, no further escalation to cohort B or C will be done. If, however, less than 70% of the 20 volunteers in cohort A reaches a clinical AND microbiological endpoint, escalation will continue to cohort B. Receives: Other: encapsulated 10^4 CFU toxigenic. C. difficile spores |
| Cohort B (vancomycin pretreatment + TCD spores) | Experimental | Volunteers in cohort B will be exposed first to 5 days of oral vancomycin pretreatment, 4 times a day 250mg, followed immediately by once a day capsule with 10^4 CFU TCD spores for 12 days. First, a pilot group of 5 volunteers will be exposed to flag safety signals. If in this pilot group TCD exposure is well tolerated and less than 70% of the volunteers (< 4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, the trial will escalate to the third cohort, cohort C. If, however, in the pilot group TCD exposure is well tolerated and at least 70% of the volunteers (≥4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, a confirmatory group of another 15 volunteers will be included in cohort B (total 20 volunteers). If in this total of 20 volunteers at least 70% (≥ 14 out of 20 volunteers) reaches a clinical AND microbiological endpoint, no further escalation to cohort C will be done. If, however, this is less then 70%, escalation continues to cohort C. Receives: Other: encapsulated 10^4 CFU toxigenic. C. difficile spores; Drug: Vancomycin |
| Cohort C (clindamycin pretreatment + TCD spores) | Experimental | Volunteers in cohort C will be exposed first to five days of oral clindamycin pretreatment, three times a day 600mg, followed immediately by once-a-day dosing of 104 CFU TCD spores (capsules) for 12 consecutive days. First, a small pilot group of five volunteers will be exposed to flag safety signals. If in this pilot group TCD exposure is well tolerated and less than 70% of the volunteers (< 4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, the trial will stop. If, however, in the pilot group TCD exposure is well tolerated and at least 70% of the volunteers (≥4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, a confirmatory group of another 15 volunteers will be included in cohort C (total 20 volunteers), after which the trial will stop. Receives: Other: encapsulated 10^4 CFU toxigenic. C. difficile spores; Drug: Clindamycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of exposure to toxigenic C. difficile spores with optional antibiotic pretreatment
number and grade of (related) adverse events
Measured: from day 0 until day 35 for cohort A and from day -5 until day 35 for cohort B and C.
Colonisation with the challenge C. difficile strain
- Proven: a positive culture of toxigenic C. difficile with the same molecular identity as the challenge strain, without symptoms of CDI.
- Probable: a positive toxin EIA on stool samples OR a positive feces tcdB-PCR, without symptoms of CDI.
Measured: on at least two timepoints from day 14 until day 35
Infection with the challenge C. difficile strain
- Proven: clinical findings compatible with CDI (clinical findings should include at least diarrhoea: Bristol stool chart type 6-7 plus ≥ 3 stools in 24 hours) and a positive culture of toxigenic C. difficile with the same molecular identity as the challenge strain
- Probable: clinical findings compatible with CDI (clinical findings should include at least diarrhoea: Bristol stool chart type 6-7 plus ≥ 3 stools in 24 hours) and a positive toxin EIA on stool samples OR a positive feces tcdB-PCR
Measured: from day 0 until day 35
Secondary outcomes (7)
Colonisation with a non-challenge C. difficile strain
Proven microbiological endpoint/colonisation with non-challenge strain: a positive culture of C. difficile with another molecular identity than the challenge strain, without symptoms of CDI.
Measured: on at least two timepoints from day 14 until day 35
Infection with non-challenge C. difficile strain
Clinical findings compatible with CDI (clinical findings should include at least diarrhoea: Bristol stool chart type 6-7 plus ≥ 3 stools in 24 hours) and a positive culture of C. difficile with another molecular identity than the challenge strain
Measured: from day 0 until day 35
Kinetics of C. difficile colonisation/infection over time
Quantitative measurement of C. difficile by qPCR at samples taken every other day
Measured: from day 0 until day 35
Systemic immune response following C. difficile colonisation and/or infection
Anti-Toxin A and anti-Toxin B neutralizing antibody titers by toxin neutralization assay (TNA) on serum samples
Measured: at day 0, 20, 35 and 84.
Antibody response following C. difficile colonisation and/or infection
ELISA for antibody responses against various antigens in serum and faecal samples
Measured: at day 0, 20, 35, 84 and first day of C. difficile infection symptoms.
Cytokine response related to C. difficile colonisation and/or infection
Cytokine measurement in serum and faecal samples
Measured: at day 0, 2, 20 and first day of C. difficile infection symptoms.
Calprotectin and potential other biomarkers related to C. difficile colonisation and/or infection
Calprotectin and potential other biomarkers for inflammation (like lactoferrin) in faecal samples
Measured: on day 0, 20 and 35
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Nov 2024
- Study start1 Mar 2025 (estimated)
- Primary completion1 Jul 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for C. DifficileStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This will be a first in human, open-label, adaptive design, escalating clinical trial, investigating the oral exposure of toxigenic C. difficile in healthy volunteers. The adaptive design is aimed at a stepwise escalation to ensure safety of trial participants and gear towards the optimal balance between endpoints and tolerability. The study will start with one cohort of volunteers, cohort A, with an option to escalate to a second cohort, cohort B, and a third cohort, cohort C, if needed. Escalation to the subsequent cohort will be performed by adding antibiotic pretreatment. Escalation will be based upon safety first and secondly upon microbiological and clinical endpoints (ideally aiming for an attack rate of 70% in both). In every cohort small pilot groups (of five volunteers each) will be used to flag safety signals and determine the escalation schedule, having the option to include 15 more participants to the same cohort or escalate to the pilot group of the subsequent cohort.
- Masking
- None (open label)
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Helmholtz Centre for Infection Research, GlaxoSmithKline, University of Oxford, University of Cologne
- Responsible party
- Principal investigator, Meta Roestenberg, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06702345
- Sponsor's protocol ID
- CloDiCHI
- Other IDs
- Grant number: 101007799
- Acronym
- CloDiCHI
- Status last verified
- Nov 2024
- First submitted
- 18 Nov 2024
- Last updated
- 22 Nov 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Nov 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Establishing a Clostridioides Difficile Controlled Human Infection Model
- ClinicalTrials.gov ID
- NCT06702345
- Acronym / sponsor ID
- CloDiCHI / CloDiCHI
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- Helmholtz Centre for Infection Research, GlaxoSmithKline, University of Oxford, University of Cologne
- Study start
- 1 Mar 2025 (estimated)
- Primary completion
- 1 Jul 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 22 Nov 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This will be a first in human, open-label, adaptive design, escalating clinical trial, investigating the oral exposure of toxigenic C. difficile in healthy volunteers. The adaptive design is aimed at a stepwise escalation to ensure safety of trial participants and gear towards the optimal balance between endpoints and tolerability. The study will start with one cohort of volunteers, cohort A, with an option to escalate to a second cohort, cohort B, and a third cohort, cohort C, if needed. Escalation to the subsequent cohort will be performed by adding antibiotic pretreatment. Escalation will be based upon safety first and secondly upon microbiological and clinical endpoints (ideally aiming for an attack rate of 70% in both). In every cohort small pilot groups (of five volunteers each) will be used to flag safety signals and determine the escalation schedule, having the option to include 15 more participants to the same cohort or escalate to the pilot group of the subsequent cohort.
| Arm | Type | Receives |
|---|---|---|
| Cohort A (TCD spores only) | Experimental | Other: encapsulated 10^4 CFU toxigenic. C. difficile sporesVolunteers in cohort A will be exposed to a once a day capsule with 10^4 CFU TCD spores for 12 days. First, a pilot group of 5 volunteers will be exposed to flag safety signals. If in this pilot group TCD exposure is well tolerated and less than 70% of the volunteers (< 4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, the trial will escalate to the second cohort, cohort B. If, however, in the pilot group TCD exposure is well tolerated and at least 70% of the volunteers (≥4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, a confirmatory group of another 15 volunteers will be included in cohort A (total 20 volunteers). If in this total of 20 volunteers sat least 70% (≥ 14 out of 20 volunteers) reaches a clinical AND microbiological endpoint, no further escalation to cohort B or C will be done. If, however, less than 70% of the 20 volunteers in cohort A reaches a clinical AND microbiological endpoint, escalation will continue to cohort B. |
| Cohort B (vancomycin pretreatment + TCD spores) | Experimental | Other: encapsulated 10^4 CFU toxigenic. C. difficile spores, Drug: VancomycinVolunteers in cohort B will be exposed first to 5 days of oral vancomycin pretreatment, 4 times a day 250mg, followed immediately by once a day capsule with 10^4 CFU TCD spores for 12 days. First, a pilot group of 5 volunteers will be exposed to flag safety signals. If in this pilot group TCD exposure is well tolerated and less than 70% of the volunteers (< 4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, the trial will escalate to the third cohort, cohort C. If, however, in the pilot group TCD exposure is well tolerated and at least 70% of the volunteers (≥4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, a confirmatory group of another 15 volunteers will be included in cohort B (total 20 volunteers). If in this total of 20 volunteers at least 70% (≥ 14 out of 20 volunteers) reaches a clinical AND microbiological endpoint, no further escalation to cohort C will be done. If, however, this is less then 70%, escalation continues to cohort C. |
| Cohort C (clindamycin pretreatment + TCD spores) | Experimental | Other: encapsulated 10^4 CFU toxigenic. C. difficile spores, Drug: ClindamycinVolunteers in cohort C will be exposed first to five days of oral clindamycin pretreatment, three times a day 600mg, followed immediately by once-a-day dosing of 104 CFU TCD spores (capsules) for 12 consecutive days. First, a small pilot group of five volunteers will be exposed to flag safety signals. If in this pilot group TCD exposure is well tolerated and less than 70% of the volunteers (< 4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, the trial will stop. If, however, in the pilot group TCD exposure is well tolerated and at least 70% of the volunteers (≥4 out of 5 volunteers) reaches a microbiological AND clinical endpoint, a confirmatory group of another 15 volunteers will be included in cohort C (total 20 volunteers), after which the trial will stop. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Subject is aged ≥18 and ≤45 years and in good health;
- Body mass index (BMI) ≥18.0 and <30.0 kg/m2;
- Subject has adequate understanding of the procedures of the study and is able and willing to abide strictly thereby;
- Subject is able to communicate well with the investigator, is willing to follow hygienic measures and instructions;
- For women of childbearing potential: subject agrees to use adequate contra-ception (see Appendix D for the different adequate contraception methods for this study) and not to breastfeed for the duration of the study;
Key exclusion criteria (20 listed)
- Any physical or psychiatric illness or conditions that could threaten or com-promise the health of the subject during the study, influence their ability to par-ticipate in the trial or interfere with the interpretation of the study results, as de-termined by the trial physician;
- Use of systemic (IV or oral) antibiotics within three months prior to screening; other microbiota influencing medication (that could influence the trial, based on the Investigator's opinion) within 1 month prior to screening visit. Prior use of topical antibiotics is permitted if there is no clinically relevant systemic ex-pected following assessment of the trial physician and are expected to be dis-continued during the start of the first study activity.
- Has had a recent hospitalization (e.g. 3 months prior to screening) and/or has someone in immediate social circle who is frequently hospitalized (≥3 times in a 12-month period) or frequently exposed to hospital settings (≥ one time a month, e.g. dialysis units);
- Regular use (defined by more than once weekly) of proton-pump inhibitors or H2-blockers during one month prior to screening;
- Chronic use of immunosuppressive drugs, e.g. systemic corticosteroids or other immune modifying drugs (with exception of oral anti-histamines and top-ical/inhaled corticosteroids);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| encapsulated 10^4 CFU toxigenic. C. difficile spores12 consecutive days of once a day a capsule with 10^4 CFU toxigenic C. difficile spores. | Other | Cohort A (TCD spores only), Cohort B (vancomycin pretreatment + TCD spores), Cohort C (clindamycin pretreatment + TCD spores) |
| Vancomycinoral vancomycin pretreatment, 4 times a day 250mg, given the five days before toxigenic C. difficile exposure. | Drug | Cohort B (vancomycin pretreatment + TCD spores) |
| Clindamycinoral clindamycin pretreatment, 3 times a day 600mg, given the five days before toxigenic C. difficile exposure | Drug | Cohort C (clindamycin pretreatment + TCD spores) |
Primary outcome
Safety of exposure to toxigenic C. difficile spores with optional antibiotic pretreatment
Time frame: from day 0 until day 35 for cohort A and from day -5 until day 35 for cohort B and C.
number and grade of (related) adverse events
Colonisation with the challenge C. difficile strain
Time frame: on at least two timepoints from day 14 until day 35
1. Proven: a positive culture of toxigenic C. difficile with the same molecular identity as the challenge strain, without symptoms of CDI. 2. Probable: a positive toxin EIA on stool samples OR a positive feces tcdB-PCR, without symptoms of CDI.
Infection with the challenge C. difficile strain
Time frame: from day 0 until day 35
1. Proven: clinical findings compatible with CDI (clinical findings should include at least diarrhoea: Bristol stool chart type 6-7 plus ≥ 3 stools in 24 hours) and a positive culture of toxigenic C. difficile with the same molecular identity as the challenge strain 2. Probable: clinical findings compatible with CDI (clinical findings should include at least diarrhoea: Bristol stool chart type 6-7 plus ≥ 3 stools in 24 hours) and a positive toxin EIA on stool samples OR a positive feces tcdB-PCR
7 secondary outcomes
Colonisation with a non-challenge C. difficile strain
Time frame: on at least two timepoints from day 14 until day 35
Infection with non-challenge C. difficile strain
Time frame: from day 0 until day 35
Kinetics of C. difficile colonisation/infection over time
Time frame: from day 0 until day 35
Systemic immune response following C. difficile colonisation and/or infection
Time frame: at day 0, 20, 35 and 84.
Antibody response following C. difficile colonisation and/or infection
Time frame: at day 0, 20, 35, 84 and first day of C. difficile infection symptoms.
Cytokine response related to C. difficile colonisation and/or infection
Time frame: at day 0, 2, 20 and first day of C. difficile infection symptoms.
Calprotectin and potential other biomarkers related to C. difficile colonisation and/or infection
Time frame: on day 0, 20 and 35
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Nov 2024.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing encapsulated 10^4 CFU toxigenic. C. difficile spores, Vancomycin and Clindamycin in people with C. Difficile and C. Difficile Infection, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 20 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 22 Nov 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Prof. dr. Meta Roestenberg (0031715262102, m.roestenberg@lumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of exposure to toxigenic C. difficile spores with optional antibiotic pretreatment (time frame: from day 0 until day 35 for cohort A and from day -5 until day 35 for cohort B and C.). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Nov 2024.