Seroprevalence of Antibodies to Surface Antigens and Toxins of Clostridioides Difficile

NCT ID: NCT05192148

Last Updated: 2023-04-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

840 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-30

Study Completion Date

2024-12-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Clostridium Difficile Infection

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

OTHER

Blinding Strategy

NONE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Patients

On the day of inclusion, as part of the research, an additional blood sample will be taken (2 dry tubes of 7 ml each).

Group Type EXPERIMENTAL

Patients

Intervention Type OTHER

On the day of inclusion, as part of the research, an additional blood sample will be taken (2 dry tubes of 7 ml each).

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Patients

On the day of inclusion, as part of the research, an additional blood sample will be taken (2 dry tubes of 7 ml each).

Intervention Type OTHER

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Fondation Hôpital Saint-Joseph

OTHER

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Alban LE MONNIER, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fondation Hôpital Saint-Joseph

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Groupe Hospitalier Paris Saint-Joseph

Paris, , France

Site Status RECRUITING

Hôpital Sainte-Marie Paris

Paris, , France

Site Status NOT_YET_RECRUITING

Centre de SSR Pierre Chevalier

Toulon, , France

Site Status NOT_YET_RECRUITING

Hôpital d'Instruction des Armées Sainte Anne,

Toulon, , France

Site Status NOT_YET_RECRUITING

Centre Hospitalier de Valenciennes

Valenciennes, , France

Site Status NOT_YET_RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

France

Central Contacts

Reach out to these primary contacts for questions about participation or study logistics.

Alban LE MONNIER, MD, PhD

Role: CONTACT

144127932 ext. +33

Helene BEAUSSIER, PharmD, PhD

Role: CONTACT

144127883 ext. +33

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Alban LE MONNIER, MD, PhD

Role: primary

144127932 ext. +33

Bernard Durand Gasselin, MD

Role: primary

Muriele PHILIP-DUTASTA, MD

Role: primary

Frédéric Janvier, MD

Role: primary

Christian CATTOEN, MD

Role: primary

References

Explore related publications, articles, or registry entries linked to this study.

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.

Reference Type BACKGROUND
PMID: 6886489 (View on PubMed)

Rousseau 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.

Reference Type BACKGROUND
PMID: 22843784 (View on PubMed)

Kyne 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.

Reference Type BACKGROUND
PMID: 10666429 (View on PubMed)

Kyne 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.

Reference Type BACKGROUND
PMID: 11213096 (View on PubMed)

Leav 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.

Reference Type BACKGROUND
PMID: 19941990 (View on PubMed)

Aboudola 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.

Reference Type BACKGROUND
PMID: 12595488 (View on PubMed)

Lowy 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.

Reference Type BACKGROUND
PMID: 20089970 (View on PubMed)

Gerding 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.

Reference Type BACKGROUND
PMID: 29538686 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

PREVADIFF

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

C.Difficile Observational Study
NCT06277999 COMPLETED