Clostridioides Difficile Controlled Human Infection Model
Trial statusNot yet recruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age18-45
SponsorLeiden University Medical Center
About this trial
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.
Eligibility criteria
This trial accepts healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Sequential
Treatments tested in this trial
encapsulated 10^4 CFU toxigenic. C. difficile spores
Other intervention12 consecutive days of once a day a capsule with 10\^4 CFU toxigenic C. difficile spores.
Vancomycin
Drugoral vancomycin pretreatment, 4 times a day 250mg, given the five days before toxigenic C. difficile exposure.
Clindamycin
Drugoral clindamycin pretreatment, 3 times a day 600mg, given the five days before toxigenic C. difficile exposure
Treatment groups
60 Participants
are divided into 3 treatment groupsGroup A: Cohort A (TCD spores only)Experimental treatment 1 intervention
Group B: Cohort B (vancomycin pretreatment + TCD spores)Experimental treatment 2 interventions
Group C: Cohort C (clindamycin pretreatment + TCD spores)Experimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Safety of exposure to toxigenic C. difficile spores with optional antibiotic pretreatment
number and grade of (related) adverse events
Time frame
from day 0 until day 35 for cohort A and from day -5 until day 35 for cohort B and C.2
Colonisation with the challenge C. difficile strain
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.
Time frame
on at least two timepoints from day 14 until day 353
Infection with the challenge C. difficile strain
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
Time frame
from day 0 until day 35Secondary outcomes
1
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.
Time frame
on at least two timepoints from day 14 until day 352
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
Time frame
from day 0 until day 353
Kinetics of C. difficile colonisation/infection over time
Quantitative measurement of C. difficile by qPCR at samples taken every other day
Time frame
from day 0 until day 354
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
Time frame
at day 0, 20, 35 and 84.Sponsors and contacts
Click on the lead sponsor to view all of their trials.
Leiden University Medical Center
Lead sponsor
Helmholtz Centre for Infection Research
Collaborator
GlaxoSmithKline
Collaborator
University of Oxford
Collaborator
University of Cologne
Collaborator
Source ClinicalTrials.gov
This trial is not recruiting at the moment. You can still explore other options: