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

This study has been completed.
Sponsor:
Information provided by:
Centre Hospitalier Universitaire de Nice
ClinicalTrials.gov Identifier:
NCT00820144
First received: January 2, 2009
Last updated: January 9, 2009
Last verified: January 2009
  Purpose

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 Intervention 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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Factorial Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Centre Hospitalier Universitaire de Nice:

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. [ Time Frame: every week during 5 weeks ] [ Designated as safety issue: Yes ]

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. [ Time Frame: every week during 5 weeks ] [ Designated as safety issue: Yes ]

Enrollment: 40
Study Start Date: April 2006
Study Completion Date: February 2007
Primary Completion Date: April 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00820144

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

No publications provided

Responsible Party: Departement de la recherche Clinique et de l'Innovation, CHU de NICE
ClinicalTrials.gov Identifier: NCT00820144     History of Changes
Other Study ID Numbers: PHRC 2003 CTB
Study First Received: January 2, 2009
Last Updated: January 9, 2009
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: French Data Protection Authority
France: Institutional Ethical Committee

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
Bacterial Infections
Gram-Negative Bacterial Infections
Vibrio Infections
Cholera Toxin
Adjuvants, Immunologic
Immunologic Factors
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 20, 2014