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

• ClinicalTrials.gov Identifier: NCT00820144
• Recruitment Status: Completed
• First Posted: January 12, 2009
• Last Update Posted: January 12, 2009
• Sponsor: Centre Hospitalier Universitaire de Nice
• Information provided by: Centre Hospitalier Universitaire de Nice

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Infection	Biological: CTB by nasal way; Biological: absorption of CTB by oral way; Biological: absorption of dukoral by oral way; Biological: absorption of CTB by sublingual way	Phase 1

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Factorial Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: Functional Exploration of the Immune Response Using the B-Subunit of Cholera Toxin Administered by Mucosal Way in Healthy Adult Volunteer: Potential Role in Development of Vaccine Processes
• Study Start Date: April 2006
• Actual Primary Completion Date: April 2006
• Actual Study Completion Date: February 2007

Arms and Interventions

Arm	Intervention/treatment
Experimental: 1; voie nasale 0.25 mg	Biological: CTB by nasal way
Experimental: 2; 0.5mg of CTB by oral way	Biological: absorption of CTB by oral way; absorption of CTB by oral way
Experimental: 3; 1mg of dukoral by oral way	Biological: absorption of dukoral by oral way; absorption of dukoral by oral way
Experimental: 4; 0.25mg of CTB by sublingual way	Biological: absorption of CTB by sublingual way; absorption of CTB by sublingual way
Experimental: 5; 1mg of CTB by sublingual way	Biological: absorption of CTB by sublingual way; absorption of CTB by sublingual way

Outcome Measures

Primary Outcome Measures :

1. The primary criteria which will estimate this immune response is the production of immunoglobulin A1, A2 and G totals specific to the CTB contained at the level of salivary secretions or produced by mononuclear cells of peripheral blood. [ Time Frame: every week during 5 weeks ]

Secondary Outcome Measures :

1. The secondary criteria of judgment are other phenotypic and functional changes induced on the immune cells present in saliva or in the blood after administration of CTB. [ Time Frame: every week during 5 weeks ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

France

Laboratoire d'anatomo-pathologie, hôpital Pasteur

Nice, France, 06000

Sponsors and Collaborators

Centre Hospitalier Universitaire de Nice

Investigators

• Principal Investigator: Paul HOFMAN, Professor; Departement d'anatomo-pathologie, CHU de Nice

More Information

• Responsible Party: Departement de la recherche Clinique et de l'Innovation, CHU de NICE
• ClinicalTrials.gov Identifier: NCT00820144
• Other Study ID Numbers: PHRC 2003 CTB
• First Posted: January 12, 2009
• Last Update Posted: January 12, 2009
• Last Verified: January 2009

Keywords provided by Centre Hospitalier Universitaire de Nice:

immune response; b-subunit of cholera toxin; mucosal way; healthy volonteers; vaccine

Additional relevant MeSH terms:

Cholera; Vibrio Infections; Gram-Negative Bacterial Infections; Bacterial Infections