Cholera Toxin B Subunit (CTB) Administered by Mucosal Way in Healthy Adult Volunteer

NCT ID: NCT00820144

Last Updated: 2009-01-12

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-04-30
• Study Completion Date: 2007-02-28

Brief Summary

It is a biomedical research without direct individual benefit, exploring and comparing the mucosal immune response after oral, nasal and sublingual administration of B-subunit of non-toxic cholera toxin (CTB) in healthy adult volunteers.

Detailed Description

The immense majority of the infections involve the mucosal surfaces as a gateway of the pathogenic agent. These mucosal surfaces are mainly represented by the gastrointestinal, respiratory and urogenital tract. These mucosal surfaces contain a highly developed immune system, which can exploit in a mucus vaccine approach to fight against infectious agents upon their penetration in the body. It has been established that to be effective against infection mucosa, a vaccine must stimulate the local immune system. This objective is reached much more efficiently when the vaccine is administered by mucosal way (oral, nasal) than by the parenteral classical way. Recent works allowed developing a new non invasive system of administration of vaccines. It is based on the mucosal administration (oral, nasal, rectal, vaginal) comprising a combination of antigen bound (either chemically or by genetic fusion) to the non-toxic subunit of cholera toxin or CTB (Cholera Toxin B subunit). This subunit has an exceptional affinity for GM1 ganglioside expressed on the surface of all nucleated cells. So, the mucosal administration (by oral or nasal route) of a low dose of an antigen linked to the CTB - Mucosal vector with immunomodulatory properties - Leads powerful secretor immune responses in the exposed mucous As well as in distant mucous, with a strong production of secretories IgA.

The developed methods of exploration have to allow to characterize the cells which live (or which migrate) in the mucous membrane investigated on the functional and phenotypic plan.

This research should lead to a range of standardized operating procedures, allowing to evaluate the immunogenicity of vaccines candidates to the mucous administration and of predictive markers of the type of immune response generated.

The main objective of the study is to analyse at the healthy voluntary subjects the systematic immunizing answer induced after nasal, oral or sublingual administration of the CTB from blood samples - the lymphoid "compartment" the most accessible at the man- from saliva and from nasal wash. The immune response after administration of the CTB By sublingual way should be comparable in that of two other ways in term of intensity of the response, however, with a different IgA / IgG report.

The secondary objective of the study is to establish a range of tests to predict the character and the intensity of this response by analyzing the expression of B cells certain surface molecules marking their future for the production of Antibodies.

It is a regional prospective monocentric study conducted in opened without direct individual profit. The study will be conducted over 3 years including 24 months of recruitment for each patient with a follow-up of 35 days and 6 months of operation data.

Conditions

Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

1

voie nasale 0.25 mg

Group Type: EXPERIMENTAL

CTB by nasal way

Intervention Type: BIOLOGICAL

2

0.5mg of CTB by oral way

Group Type: EXPERIMENTAL

absorption of CTB by oral way

Intervention Type: BIOLOGICAL

absorption of CTB by oral way

3

1mg of dukoral by oral way

Group Type: EXPERIMENTAL

absorption of dukoral by oral way

Intervention Type: BIOLOGICAL

absorption of dukoral by oral way

4

0.25mg of CTB by sublingual way

Group Type: EXPERIMENTAL

absorption of CTB by sublingual way

Intervention Type: BIOLOGICAL

absorption of CTB by sublingual way

5

1mg of CTB by sublingual way

Group Type: EXPERIMENTAL

absorption of CTB by sublingual way

Intervention Type: BIOLOGICAL

absorption of CTB by sublingual way

Interventions

CTB by nasal way

Intervention Type: BIOLOGICAL

absorption of CTB by oral way

absorption of CTB by oral way

Intervention Type: BIOLOGICAL

absorption of dukoral by oral way

absorption of dukoral by oral way

Intervention Type: BIOLOGICAL

absorption of CTB by sublingual way

absorption of CTB by sublingual way

Intervention Type: BIOLOGICAL

absorption of CTB by sublingual way

absorption of CTB by sublingual way

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

• Adult male between 18 and 50 years,
• Adult female aged 18 to 50 years under oral contraception (pill) for at least 6 months, or IUD for at least 6 under, and agreeing to carry out a pregnancy test during the initial clinical visit
• Affiliate or entitled to Social Security
• Signing the informed consent of the volunteer

Exclusion Criteria

• Seropositive patient for HIV, Hepatitis B, Hepatitis C (oral questioning)
• Pregnant Woman, parturient or breast-feeding
• News hospitalized for other reasons that the research
• Minor, Major under supervision
• Participation in a current or recent study or at present in period of exclusion

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Centre Hospitalier Universitaire de Nice

OTHER

Sponsor Role: lead

Responsible Party

CHU de NICE

Principal Investigators

Paul HOFMAN, Professor

Role: PRINCIPAL_INVESTIGATOR

Departement d'anatomo-pathologie, CHU de Nice

Locations

Laboratoire d'anatomo-pathologie, hôpital Pasteur

Nice, , France

Countries

France

Other Identifiers

PHRC 2003 CTB

Identifier Type: -

Identifier Source: org_study_id