Cholera Toxin B Subunit (CTB) Administered by Mucosal Way in Healthy Adult Volunteer
Primary Purpose
Infection
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
CTB by nasal way
absorption of CTB by oral way
absorption of dukoral by oral way
absorption of CTB by sublingual way
absorption of CTB by sublingual way
Sponsored by
About this trial
This is an interventional basic science trial for Infection focused on measuring immune response, b-subunit of cholera toxin, mucosal way, healthy volonteers, vaccine
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
Sites / Locations
- Laboratoire d'anatomo-pathologie, hôpital Pasteur
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm 5
Arm Type
Experimental
Experimental
Experimental
Experimental
Experimental
Arm Label
1
2
3
4
5
Arm Description
voie nasale 0.25 mg
0.5mg of CTB by oral way
1mg of dukoral by oral way
0.25mg of CTB by sublingual way
1mg of CTB by sublingual way
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
NCT ID
NCT00820144
First Posted
January 2, 2009
Last Updated
January 9, 2009
Sponsor
Centre Hospitalier Universitaire de Nice
1. Study Identification
Unique Protocol Identification Number
NCT00820144
Brief Title
Cholera Toxin B Subunit (CTB) Administered by Mucosal Way in Healthy Adult Volunteer
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 Type
Interventional
2. Study Status
Record Verification Date
January 2009
Overall Recruitment Status
Completed
Study Start Date
April 2006 (undefined)
Primary Completion Date
April 2006 (Actual)
Study Completion Date
February 2007 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Centre Hospitalier Universitaire de Nice
4. Oversight
Data Monitoring Committee
No
5. 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.
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infection
Keywords
immune response, b-subunit of cholera toxin, mucosal way, healthy volonteers, vaccine
7. Study Design
Primary Purpose
Basic Science
Study Phase
Phase 1
Interventional Study Model
Factorial Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
40 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
voie nasale 0.25 mg
Arm Title
2
Arm Type
Experimental
Arm Description
0.5mg of CTB by oral way
Arm Title
3
Arm Type
Experimental
Arm Description
1mg of dukoral by oral way
Arm Title
4
Arm Type
Experimental
Arm Description
0.25mg of CTB by sublingual way
Arm Title
5
Arm Type
Experimental
Arm Description
1mg of CTB by sublingual way
Intervention Type
Biological
Intervention Name(s)
CTB by nasal way
Intervention Type
Biological
Intervention Name(s)
absorption of CTB by oral way
Intervention Description
absorption of CTB by oral way
Intervention Type
Biological
Intervention Name(s)
absorption of dukoral by oral way
Intervention Description
absorption of dukoral by oral way
Intervention Type
Biological
Intervention Name(s)
absorption of CTB by sublingual way
Intervention Description
absorption of CTB by sublingual way
Intervention Type
Biological
Intervention Name(s)
absorption of CTB by sublingual way
Intervention Description
absorption of CTB by sublingual way
Primary Outcome Measure Information:
Title
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 Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Paul HOFMAN, Professor
Organizational Affiliation
Departement d'anatomo-pathologie, CHU de Nice
Official's Role
Principal Investigator
Facility Information:
Facility Name
Laboratoire d'anatomo-pathologie, hôpital Pasteur
City
Nice
ZIP/Postal Code
06000
Country
France
12. IPD Sharing Statement
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Cholera Toxin B Subunit (CTB) Administered by Mucosal Way in Healthy Adult Volunteer
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