Monoclonal Antibodies in Clostridium Difficile Infection

NCT ID: NCT04874623

Last Updated: 2022-10-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-11-29
• Study Completion Date: 2022-09-28

Brief 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. 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.

C. 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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

CDI

Group Type: EXPERIMENTAL

Collection of peripheral blood mononuclear cells

Intervention Type: OTHER

Analysis of specific memory B cells in CDI patients

Interventions

Collection of peripheral blood mononuclear cells

Analysis of specific memory B cells in CDI patients

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• pregnant or nursing women
• adult under guardianship
• Ileus
• Peritonitis
• Pseudomembranous colitis
• Hemodynamic instability
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Institut Pasteur

INDUSTRY

Sponsor Role: collaborator

Assistance Publique - Hôpitaux de Paris

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Baptiste Hervier

Role: PRINCIPAL_INVESTIGATOR

Assistance Publique - Hôpitaux de Paris

Locations

Maladies infectieuses et tropicales, Hôpital Pitié-Salpêtrière

Paris, , France

Countries

France

Other Identifiers

APHP180354

Identifier Type: -

Identifier Source: org_study_id