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

C

Centre Hospitalier Universitaire de Nice

Status and phase

Completed
Phase 1

Conditions

Infection

Treatments

Biological: absorption of CTB by oral way
Biological: absorption of CTB by sublingual way
Biological: absorption of dukoral by oral way
Biological: CTB by nasal way

Study type

Interventional

Funder types

Other

Identifiers

NCT00820144
PHRC 2003 CTB

Details and patient eligibility

About

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.

Full 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.

Enrollment

40 patients

Sex

All

Ages

18 to 50 years old

Volunteers

Accepts Healthy Volunteers

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

Trial design

Primary purpose

Basic Science

Allocation

Randomized

Interventional model

Factorial Assignment

Masking

None (Open label)

40 participants in 5 patient groups

1
Experimental group
Description:
voie nasale 0.25 mg
Treatment:
Biological: CTB by nasal way
2
Experimental group
Description:
0.5mg of CTB by oral way
Treatment:
Biological: absorption of CTB by oral way
3
Experimental group
Description:
1mg of dukoral by oral way
Treatment:
Biological: absorption of dukoral by oral way
4
Experimental group
Description:
0.25mg of CTB by sublingual way
Treatment:
Biological: absorption of CTB by sublingual way
Biological: absorption of CTB by sublingual way
5
Experimental group
Description:
1mg of CTB by sublingual way
Treatment:
Biological: absorption of CTB by sublingual way
Biological: absorption of CTB by sublingual way

Trial contacts and locations

1

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Data sourced from clinicaltrials.gov

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