Clostridium InfectionIgAClostridiumNCT04874623
Monoclonal Antibodies in Clostridium Difficile Infection
A study testing Collection of peripheral blood mononuclear cells in people with Clostridium Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Immunoglobulin A (IgA), the major mucosal antibody, plays a key role in maintaining diversity of the intestinal microbiota and eliminating intestinal pathogens. Dysbiosis is an important risk factor for Clostridium difficile infection, which is the leading cause of nosocomial diarrhea in industrialized countries. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Clostridium Infection
- What is being tested?
- Collection of peripheral blood mononuclear cells
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteFrance
- Study dates
- 29 Nov 2021to 28 Sep 2022
- 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 of age
- diarrhea and/or abdominal pain.
- Presence of C. difficile toxins in feces
- Patient having dated and signed informed consent.
Who cannot join
- pregnant or nursing women
- adult under guardianship
- Ileus
- Peritonitis
- Pseudomembranous colitis
- Hemodynamic instability
Show all 15Show fewer
- Fever ≥ 38.5°C
- Shivers
- Respiratory failure
- Leukocytosis > 15x109/L
- Serum creatinin >50% reference values)
- Serum lactate > 5mM
- Serum Albumine < 30g/l
- Other diarrhea cause
- Humoral immunodeficiency
Trial locations and contacts
1 site in 1 country.
France1 site
Maladies infectieuses et tropicales, Hôpital Pitié-Salpêtrière
Paris, 75013
About this study
Official title: Identification of IgA Monoclonal Antibodies Anti-Clostridium Difficile Surface Proteins
Immunoglobulin A (IgA), the major mucosal antibody, plays a key role in maintaining diversity of the intestinal microbiota and eliminating intestinal pathogens. Dysbiosis is an important risk factor for Clostridium difficile infection, which is the leading cause of nosocomial diarrhea in industrialized countries. This study aims to develop IgA monoclonal antibodies targeting C. difficile surface proteins.
Read the detailed description
Immunoglobulin A (IgA), the major mucosal antibody, plays a key role in maintaining the diversity of the intestinal microbiota and eliminating intestinal pathogens. They modulate microbiota composition and also commensal bacteria homeostasis, thus promoting a symbiotic relationship. These observations, derived from mouse studies, open promising therapeutic perspectives: IgA could be used to restore or maintain a healthy microbiota in individuals suffering from intestinal dysbiosis. Specific to a pathogen, IgA can also be considered as an alternative to antibiotics by mimicking a physiological elimination.
Abnormalities in microbial diversity (i.e. dysbiosis) have been associated in humans with various diseases such as Clostridium difficile infection, which is the leading cause of nosocomial diarrhea in industrialized countries. The incidence of CDI has dramatically raised since the early 2000s, with an increasing severity. Current treatments are limited to the administration of antibiotics that unbalance the intestinal microbiota, a risk factor for relapse. These frequent relapses contribute to the severity and chronicity of the infection.
This study aims to generate human IgA-type antibodies targeting C. difficile surface proteins with neutralizing and/or protective activity. These antibodies will be selected against surface proteins involved in the early stages of colonization. After injection or ingestion, these IgA antibodies should reproduce physiological mucosal immunity, treat severe forms and prevent the occurrence of C. difficile relapses while limiting deleterious effects on the intestinal microbiota.
- difficile-specific B cells will be selected from infected patients. After selection of the most neutralizing IgA antibodies in vitro, these will be administered to C. difficile infected mice.
- Conditions
- Clostridium Infection
- Being tested
- Collection of peripheral blood mononuclear cells
- Keywords
- Clostridium difficile infection, Therapeutic monoclonal antibodies
- Medical subject headings
- Clostridium Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Collection of peripheral blood mononuclear cellsOther
Analysis of specific memory B cells in CDI patients
| Study group | Role | What they receive |
|---|---|---|
| CDI | Experimental | Not described Receives: Other: Collection of peripheral blood mononuclear cells |
What is being measured
The primary outcome is the main question the study is designed to answer.
Generate C. difficile specific antibodies from circulating memory B lymphocytes of C. difficile patients.
The presence of SlpA and Cwp84 specific memory B cells will be assessed from a single sample per patient. After separation of blood mononuclear cells, specific memory B cells will be selected using microfluidic drop technology. The variable VH and VL fragments of the immunoglobulins, which define the specificity of the antibodies, will be sequenced for each selected B cell. The corresponding antibodies will then be produced in a well-established cell line.
Measured: From the blood samples taken between Day 1 and Day 7 after the diagnostic of CDI
Secondary outcomes (2)
Antibody affinity assessment
The affinity of the antibodies will be evaluated by surface plasmon resonance (Biacore®).
Measured: From the blood samples taken between Day1 and Day7 after the diagnostic of CDI
Neutralizing capacity evaluation affinity
The neutralizing activity will be evaluated in vitro: the capacity of the antibodies to decrease the proliferation of the bacteria (in liquid culture), to decrease its mobility (solid culture), to inhibit biofilm formation and to inhibit its adhesion to the surface of intestinal epithelial cells (quantified using the Caco-213 line).
Measured: From the blood samples taken between Day1 and Day7 after the diagnostic of CDI
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 May 2021
- Study start29 Nov 2021
- Primary completion29 Nov 2021
- Study completion28 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Clostridium InfectionStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- 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
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- Institut Pasteur
- Responsible party
- Sponsor
- Investigators
- Baptiste Hervier, Principal investigator, Assistance Publique - Hôpitaux de Paris
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04874623
- Sponsor's protocol ID
- APHP180354
- Acronym
- IgAClostridium
- Status last verified
- Sep 2022
- First submitted
- 22 Sep 2020
- Last updated
- 4 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- 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 4 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Identification of IgA Monoclonal Antibodies Anti-Clostridium Difficile Surface Proteins
- ClinicalTrials.gov ID
- NCT04874623
- Acronym / sponsor ID
- IgAClostridium / APHP180354
- Conditions
- Clostridium Infection
- Keywords
- Clostridium difficile infection, Therapeutic monoclonal antibodies
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- Institut Pasteur
- Study start
- 29 Nov 2021 (actual)
- Primary completion
- 29 Nov 2021 (actual)
- Study completion
- 28 Sep 2022 (actual)
- First posted
- 6 May 2021 (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.
Immunoglobulin A (IgA), the major mucosal antibody, plays a key role in maintaining diversity of the intestinal microbiota and eliminating intestinal pathogens. Dysbiosis is an important risk factor for Clostridium difficile infection, which is the leading cause of nosocomial diarrhea in industrialized countries. This study aims to develop IgA monoclonal antibodies targeting C. difficile surface proteins.
Detailed description
Immunoglobulin A (IgA), the major mucosal antibody, plays a key role in maintaining the diversity of the intestinal microbiota and eliminating intestinal pathogens. They modulate microbiota composition and also commensal bacteria homeostasis, thus promoting a symbiotic relationship. These observations, derived from mouse studies, open promising therapeutic perspectives: IgA could be used to restore or maintain a healthy microbiota in individuals suffering from intestinal dysbiosis. Specific to a pathogen, IgA can also be considered as an alternative to antibiotics by mimicking a physiological elimination.
Abnormalities in microbial diversity (i.e. dysbiosis) have been associated in humans with various diseases such as Clostridium difficile infection, which is the leading cause of nosocomial diarrhea in industrialized countries. The incidence of CDI has dramatically raised since the early 2000s, with an increasing severity. Current treatments are limited to the administration of antibiotics that unbalance the intestinal microbiota, a risk factor for relapse. These frequent relapses contribute to the severity and chronicity of the infection.
This study aims to generate human IgA-type antibodies targeting C. difficile surface proteins with neutralizing and/or protective activity. These antibodies will be selected against surface proteins involved in the early stages of colonization. After injection or ingestion, these IgA antibodies should reproduce physiological mucosal immunity, treat severe forms and prevent the occurrence of C. difficile relapses while limiting deleterious effects on the intestinal microbiota.
- difficile-specific B cells will be selected from infected patients. After selection of the most neutralizing IgA antibodies in vitro, these will be administered to C. difficile infected mice.
Study design
- Primary purpose
- Basic science
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| CDI | Experimental | Other: Collection of peripheral blood mononuclear cells |
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 of age
- diarrhea and/or abdominal pain.
- Presence of C. difficile toxins in feces
- Patient having dated and signed informed consent.
Key exclusion criteria (15 listed)
- pregnant or nursing women
- adult under guardianship
- Ileus
- Peritonitis
- Pseudomembranous colitis
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 |
|---|---|---|
| Collection of peripheral blood mononuclear cellsAnalysis of specific memory B cells in CDI patients | Other | CDI |
Primary outcome
Generate C. difficile specific antibodies from circulating memory B lymphocytes of C. difficile patients.
Time frame: From the blood samples taken between Day 1 and Day 7 after the diagnostic of CDI
The presence of SlpA and Cwp84 specific memory B cells will be assessed from a single sample per patient. After separation of blood mononuclear cells, specific memory B cells will be selected using microfluidic drop technology. The variable VH and VL fragments of the immunoglobulins, which define the specificity of the antibodies, will be sequenced for each selected B cell. The corresponding antibodies will then be produced in a well-established cell line.
2 secondary outcomes
Antibody affinity assessment
Time frame: From the blood samples taken between Day1 and Day7 after the diagnostic of CDI
Neutralizing capacity evaluation affinity
Time frame: From the blood samples taken between Day1 and Day7 after the diagnostic of CDI
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Oct 2022.
- 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. This study is not recruiting at the moment.
Baptiste Hervier principal investigator
Assistance Publique - Hôpitaux de Paris
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Collection of peripheral blood mononuclear cells in people with Clostridium Infection, run by Assistance Publique - Hôpitaux de Paris at 1 site 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 15 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: finished, as of the sponsor's last update on 4 Oct 2022. 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 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Generate C. difficile specific antibodies from circulating memory B lymphocytes of C. difficile patients. (time frame: From the blood samples taken between Day 1 and Day 7 after the diagnostic of CDI). 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 4 Oct 2022.