Clostridium Difficile InfectionPREVADIFFNCT05192148
Seroprevalence of Antibodies to Surface Antigens and Toxins of Clostridioides Difficile
A study testing Patients in people with Clostridium Difficile Infection, run by Fondation Hôpital Saint-Joseph at 5 sites in France.
Trial summary
Data on the seroprevalence of antibodies to Clostridioides difficile surface proteins and toxins are scarce. In 1983, Viscidi et al. showed that antibodies to C. difficile toxins A and B were detected in 60 to 70% of an adult population. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Difficile Infection
- What is being tested?
- Patients
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 840 participants
- Where
- 5 sitesFrance
- Study dates
- 30 Nov 2021to 30 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patient (≥ 18 years) hospitalized in targeted short-stay (MCO) and long-stay (LTC) services for each of the three identified regions
- French-speaking patient
- Patient affiliated to the social security system or, failing that, to another health insurance system
- Patient able to give free, informed and written consent
Who cannot join
- History of blood transfusion, vascular filling, dialysis or polyvalent immunoglobulin infusion.
- Patient deprived of liberty
- Patient under court protection
- Patient in an emergency situation
- Patients unable to give personal consent, including adults under guardianship
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
France5 sites, 5 recruiting
- Recruiting
Groupe Hospitalier Paris Saint-Joseph
Paris, 75014
Alban LE MONNIER, MD, PhD, 144127932 ext. +33, alemonnier@ghpsj.fr
- Not yet recruiting
Hôpital Sainte-Marie Paris
Paris, 75014
Bernard Durand Gasselin, MD
- Not yet recruiting
Centre de SSR Pierre Chevalier
Toulon
Muriele PHILIP-DUTASTA, MD
- Not yet recruiting
Hôpital d'Instruction des Armées Sainte Anne,
Toulon
Frédéric Janvier, MD
- Not yet recruiting
Centre Hospitalier de Valenciennes
Valenciennes
Christian CATTOEN, MD
About this study
Data on the seroprevalence of antibodies to Clostridioides difficile surface proteins and toxins are scarce.
In 1983, Viscidi et al. showed that antibodies to C. difficile toxins A and B were detected in 60 to 70% of an adult population. Two-thirds of the adults tested had a serological trace, probably linked to a previous encounter with C. difficile.
Read more
One of the hypotheses raised would be that exposure to this pathogen occurs very early and regularly throughout our lives. Indeed, in this study, antibodies to C. difficile toxins were detected from early childhood and persisted over time even after 60 years. The antibody response did not appear to vary with age or terrain. However, these results were only qualitative and did not allow for inter-individual variations due to the limitations of the techniques used at the time. Finally, in this work, it was important to underline that the neutralizing character of the cytotoxic effect of toxins on cell culture was not observed in all patients.
Since this seminal work, several studies have shown that the host immune response plays a central role in the pathophysiology of C. difficile infections (CDI). In 2000, Kyne et al. showed that after colonization with a toxigenic C. difficile strain, patients with asymptomatic carriage had significantly higher serum levels of IgG directed against toxin A than patients who developed disease. Subsequently, they also showed in 2001 that a serum response directed against toxin A after a first episode of CDI was associated with less recurrence. Finally, Leav et al. showed in 2010 that a serum response directed against C. difficile toxin B was also associated with protection against recurrent forms.
Several studies have also suggested that the host immune response, this time directed against colonization factors, could also play a major role in the evolution and prognosis of CDI. In a previous study, investigators showed a significant difference in the level of anti-SlpA antibodies (S-layer component) between CDI patients and control patients.
At the same time, the epidemiology of CDI has changed since 2003 due to the emergence of a new epidemic and hypervirulent strain (PCR ribotype 027) producing a third toxin, the binary toxin. The humoral response to this toxin remains poorly described to date.
On the basis of these numerous studies, new therapeutic immunization strategies (active or passive) aimed at neutralizing the action of C. difficile toxins and colonization factors have been or are being developed.
However, it remains to identify the patients likely to benefit from these innovative strategies. This was the main objective of the SERODIFF study (currently being finalized), which identified certain patient profiles in which no seroconversion or isotype class switching of antibodies was observed following CDI. The absence of neutralizing antibody production would seem to correlate with recurrent forms. Thus, these patients would be those who could be eligible for a passive immunization strategy such as the administration of anti-toxin B monoclonal antibodies, bezlotoxumab, recently marketed in France.
In this study, investigators aim to evaluate the seroprevalence stratified by age group, sex and by the main risk factors for CDI. Furthermore, the neutralizing and protective effect of the detected antibodies against C. difficile virulence factors will be studied.
- Conditions
- Clostridium Difficile Infection
- Being tested
- Patients
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PatientsOther
On the day of inclusion, as part of the research, an additional blood sample will be taken (2 dry tubes of 7 ml each).
| Study group | Role | What they receive |
|---|---|---|
| Patients | Experimental | On the day of inclusion, as part of the research, an additional blood sample will be taken (2 dry tubes of 7 ml each). Receives: Other: Patients |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall seroprevalence of antibodies to the major virulence factors of Clostridioides difficile
This outcome corresponds to the percentage of patients with antibodies detected against each of the antigens studied (toxins and Clostridioides difficile colonization factors).
Measured: Day 1
Secondary outcomes (3)
Immune response profiles
This outcome corresponds to the comparison of antibody positivity rates according to different groups such as gender, age groups, geographical location and community or hospital status.
Measured: Day 1
Observed immune responses
This outcome corresponds to the distribution of serum antibody titers to each antigen of interest (IgG and IgM) and rate of patients with neutralizing antibodies (cell culture cytotoxicity test) among patients with detectable antibodies.
Measured: Day 1
Determination of the seroprevalence of antibodies directed specifically against binary toxins
This outcome corresponds to the percentage of patients with antibodies to C. difficile binary toxins.
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jan 2022
- Study start30 Nov 2021
- Primary completion30 Dec 2023 (estimated)
- Study completion30 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Clostridium Difficile InfectionStudies 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
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 840 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fondation Hôpital Saint-Joseph
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Alban LE MONNIER, MD, PhD, Principal investigator, Fondation Hôpital Saint-Joseph
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05192148
- Sponsor's protocol ID
- PREVADIFF
- Acronym
- PREVADIFF
- Status last verified
- Apr 2023
- First submitted
- 30 Dec 2021
- Last updated
- 7 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Viscidi R, Laughon BE, Yolken R, Bo-Linn P, Moench T, Ryder RW, Bartlett JG. Serum antibody response to toxins A and B of Clostridium difficile. J Infect Dis. 1983 Jul;148(1):93-100. doi: 10.1093/infdis/148.1.93.
PubMed 6886489Rousseau C, Poilane I, De Pontual L, Maherault AC, Le Monnier A, Collignon A. Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin Infect Dis. 2012 Nov;55(9):1209-15. doi: 10.1093/cid/cis637. Epub 2012 Jul 25.
PubMed 22843784Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000 Feb 10;342(6):390-7. doi: 10.1056/NEJM200002103420604.
PubMed 10666429Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001 Jan 20;357(9251):189-93. doi: 10.1016/S0140-6736(00)03592-3.
PubMed 11213096Leav BA, Blair B, Leney M, Knauber M, Reilly C, Lowy I, Gerding DN, Kelly CP, Katchar K, Baxter R, Ambrosino D, Molrine D. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010 Jan 22;28(4):965-9. doi: 10.1016/j.vaccine.2009.10.144. Epub 2009 Nov 24.
PubMed 19941990Aboudola S, Kotloff KL, Kyne L, Warny M, Kelly EC, Sougioultzis S, Giannasca PJ, Monath TP, Kelly CP. Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A. Infect Immun. 2003 Mar;71(3):1608-10. doi: 10.1128/IAI.71.3.1608-1610.2003.
PubMed 12595488Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, Nichol G, Thomas WD Jr, Leney M, Sloan S, Hay CA, Ambrosino DM. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010 Jan 21;362(3):197-205. doi: 10.1056/NEJMoa0907635.
PubMed 20089970Gerding DN, Kelly CP, Rahav G, Lee C, Dubberke ER, Kumar PN, Yacyshyn B, Kao D, Eves K, Ellison MC, Hanson ME, Guris D, Dorr MB. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-656. doi: 10.1093/cid/ciy171.
PubMed 29538686
Study at a glance
From the registry record, last updated by the sponsor on 7 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Seroprevalence of Antibodies to Surface Antigens and Toxins of Clostridioides Difficile
- ClinicalTrials.gov ID
- NCT05192148
- Acronym / sponsor ID
- PREVADIFF / PREVADIFF
- Conditions
- Clostridium Difficile Infection
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 840 participants (estimated)
- Lead sponsor
- Fondation Hôpital Saint-JosephUniversity, hospital or other
- Study start
- 30 Nov 2021 (actual)
- Primary completion
- 30 Dec 2023 (estimated)
- Study completion
- 30 Dec 2024 (estimated)
- First posted
- 14 Jan 2022 (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.
Data on the seroprevalence of antibodies to Clostridioides difficile surface proteins and toxins are scarce.
In 1983, Viscidi et al. showed that antibodies to C. difficile toxins A and B were detected in 60 to 70% of an adult population. Two-thirds of the adults tested had a serological trace, probably linked to a previous encounter with C. difficile.
One of the hypotheses raised would be that exposure to this pathogen occurs very early and regularly throughout our lives. Indeed, in this study, antibodies to C. difficile toxins were detected from early childhood and persisted over time even after 60 years. The antibody response did not appear to vary with age or terrain. However, these results were only qualitative and did not allow for inter-individual variations due to the limitations of the techniques used at the time. Finally, in this work, it was important to underline that the neutralizing character of the cytotoxic effect of toxins on cell culture was not observed in all patients.
Since this seminal work, several studies have shown that the host immune response plays a central role in the pathophysiology of C. difficile infections (CDI). In 2000, Kyne et al. showed that after colonization with a toxigenic C. difficile strain, patients with asymptomatic carriage had significantly higher serum levels of IgG directed against toxin A than patients who developed disease. Subsequently, they also showed in 2001 that a serum response directed against toxin A after a first episode of CDI was associated with less recurrence. Finally, Leav et al. showed in 2010 that a serum response directed against C. difficile toxin B was also associated with protection against recurrent forms.
Several studies have also suggested that the host immune response, this time directed against colonization factors, could also play a major role in the evolution and prognosis of CDI. In a previous study, investigators showed a significant difference in the level of anti-SlpA antibodies (S-layer component) between CDI patients and control patients.
At the same time, the epidemiology of CDI has changed since 2003 due to the emergence of a new epidemic and hypervirulent strain (PCR ribotype 027) producing a third toxin, the binary toxin. The humoral response to this toxin remains poorly described to date.
On the basis of these numerous studies, new therapeutic immunization strategies (active or passive) aimed at neutralizing the action of C. difficile toxins and colonization factors have been or are being developed.
However, it remains to identify the patients likely to benefit from these innovative strategies. This was the main objective of the SERODIFF study (currently being finalized), which identified certain patient profiles in which no seroconversion or isotype class switching of antibodies was observed following CDI. The absence of neutralizing antibody production would seem to correlate with recurrent forms. Thus, these patients would be those who could be eligible for a passive immunization strategy such as the administration of anti-toxin B monoclonal antibodies, bezlotoxumab, recently marketed in France.
In this study, investigators aim to evaluate the seroprevalence stratified by age group, sex and by the main risk factors for CDI. Furthermore, the neutralizing and protective effect of the detected antibodies against C. difficile virulence factors will be studied.
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Patients | Experimental | Other: PatientsOn the day of inclusion, as part of the research, an additional blood sample will be taken (2 dry tubes of 7 ml each). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Adult patient (≥ 18 years) hospitalized in targeted short-stay (MCO) and long-stay (LTC) services for each of the three identified regions
- French-speaking patient
- Patient affiliated to the social security system or, failing that, to another health insurance system
- Patient able to give free, informed and written consent
Key exclusion criteria (5 listed)
- History of blood transfusion, vascular filling, dialysis or polyvalent immunoglobulin infusion.
- Patient deprived of liberty
- Patient under court protection
- Patient in an emergency situation
- Patients unable to give personal consent, including adults under guardianship
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 |
|---|---|---|
| PatientsOn the day of inclusion, as part of the research, an additional blood sample will be taken (2 dry tubes of 7 ml each). | Other | Patients |
Primary outcome
Overall seroprevalence of antibodies to the major virulence factors of Clostridioides difficile
Time frame: Day 1
This outcome corresponds to the percentage of patients with antibodies detected against each of the antigens studied (toxins and Clostridioides difficile colonization factors).
3 secondary outcomes
Immune response profiles
Time frame: Day 1
Observed immune responses
Time frame: Day 1
Determination of the seroprevalence of antibodies directed specifically against binary toxins
Time frame: Day 1
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Apr 2023.
- Background: PubMed 6886489Viscidi R, Laughon BE, Yolken R, Bo-Linn P, Moench T, Ryder RW, Bartlett JG. Serum antibody response to toxins A and B of Clostridium difficile. J Infect Dis. 1983 Jul;148(1):93-100. doi: 10.1093/infdis/148.1.93.
- Background: PubMed 22843784Rousseau C, Poilane I, De Pontual L, Maherault AC, Le Monnier A, Collignon A. Clostridium difficile carriage in healthy infants in the community: a potential reservoir for pathogenic strains. Clin Infect Dis. 2012 Nov;55(9):1209-15. doi: 10.1093/cid/cis637. Epub 2012 Jul 25.
- Background: PubMed 10666429Kyne L, Warny M, Qamar A, Kelly CP. Asymptomatic carriage of Clostridium difficile and serum levels of IgG antibody against toxin A. N Engl J Med. 2000 Feb 10;342(6):390-7. doi: 10.1056/NEJM200002103420604.
- Background: PubMed 11213096Kyne L, Warny M, Qamar A, Kelly CP. Association between antibody response to toxin A and protection against recurrent Clostridium difficile diarrhoea. Lancet. 2001 Jan 20;357(9251):189-93. doi: 10.1016/S0140-6736(00)03592-3.
- Background: PubMed 19941990Leav BA, Blair B, Leney M, Knauber M, Reilly C, Lowy I, Gerding DN, Kelly CP, Katchar K, Baxter R, Ambrosino D, Molrine D. Serum anti-toxin B antibody correlates with protection from recurrent Clostridium difficile infection (CDI). Vaccine. 2010 Jan 22;28(4):965-9. doi: 10.1016/j.vaccine.2009.10.144. Epub 2009 Nov 24.
- Background: PubMed 12595488Aboudola S, Kotloff KL, Kyne L, Warny M, Kelly EC, Sougioultzis S, Giannasca PJ, Monath TP, Kelly CP. Clostridium difficile vaccine and serum immunoglobulin G antibody response to toxin A. Infect Immun. 2003 Mar;71(3):1608-10. doi: 10.1128/IAI.71.3.1608-1610.2003.
- Background: PubMed 20089970Lowy I, Molrine DC, Leav BA, Blair BM, Baxter R, Gerding DN, Nichol G, Thomas WD Jr, Leney M, Sloan S, Hay CA, Ambrosino DM. Treatment with monoclonal antibodies against Clostridium difficile toxins. N Engl J Med. 2010 Jan 21;362(3):197-205. doi: 10.1056/NEJMoa0907635.
- Background: PubMed 29538686Gerding DN, Kelly CP, Rahav G, Lee C, Dubberke ER, Kumar PN, Yacyshyn B, Kao D, Eves K, Ellison MC, Hanson ME, Guris D, Dorr MB. Bezlotoxumab for Prevention of Recurrent Clostridium difficile Infection in Patients at Increased Risk for Recurrence. Clin Infect Dis. 2018 Aug 16;67(5):649-656. doi: 10.1093/cid/ciy171.
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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. This study is not recruiting at the moment.
Alban LE MONNIER, MD, PhD principal investigator
Fondation Hôpital Saint-Joseph
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Patients in people with Clostridium Difficile Infection, run by Fondation Hôpital Saint-Joseph at 5 sites in France.
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 4 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 7 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 sites in France. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alban LE MONNIER, MD, PhD (144127932 ext. +33, alemonnier@ghpsj.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall seroprevalence of antibodies to the major virulence factors of Clostridioides difficile (time frame: Day 1). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05192148, which also lists 8 linked publications.
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 7 Apr 2023.