Challenge study to determine the protective efficacy of a single oral dose of the attenuated 638 strain.

• Register: RPCEC
• Last refreshed on: 29 April 2013
• Main ID: RPCEC00000072
• Date of registration: 12/09/2008
• Primary sponsor: Finlay Institute
• Public title: Challenge study to determine the protective efficacy of a single oral dose of the attenuated 638 strain.
• Scientific title: Randomized, controlled, double-blind cholera challenge study with a virulent Vibrio cholerae strain to determine the protective efficacy of a single oral dose of 10E9 CFU of the live attenuated 638 Vibrio cholerae strain, in healthy, male, adult volunteers.
• Date of first enrolment: 29/01/2003
• Target sample size: 27
• Recruitment status: Closed
• URL: http://registroclinico.sld.cu/trials/RPCEC00000072-En
• Study type: Interventional
• Study design: Randomization: Randomized Controlled Trial Blinding: Double Blind Placebo: Placebo Assignment: Parallel Purpose: Treatment

Countries of recruitment

Cuba

Contacts

• Name: Dra. Hilda García Sánchez
• Affiliation: Finlay Institute

• Name: Dr. Rodrigo Valera Fernández
• Affiliation: Finlay Institute

Key inclusion & exclusion criteria

Inclusion criteria: 1-Healthy man between 18 to 40 years of age. 2-Free from obvious health problems as established by medical history, clinical examination, laboratory tests and psychometric tests before entering into the study. 3-Written informed consent obtained from the subjects.
Exclusion criteria: 1-Previous history of immunodeficiency. 2-Cardiovascular, respiratory, renal, hematological, hepatic, gastrointestinal, neurological, endocrine, and psychiatric diseases or reticuloendothelial system disorders detected during the clinical examination or by laboratory tests. 3-Allergy to tetracyclines. 4-Previous cholera vaccination or challenge with V. cholera virulent strain (applicable only to the stage I). 5-Administration of immunoglobulins and/or antibiotics within 30 days preceding the treatment. 6-Positive serological test for human HIV-1-2 virus antibodies. 7-Positive serological test for human hepatitis B surface antigen, or hepatitis A and C antibodies. 8-Stool cultures positive for an enteric pathogen. 9-Chronic administration (defined as more than 14 days) of immunosuppressants or other immune-modifying drugs prior to the treatment. Inhaled and topical steroids are allowed. 10-Administration of a vaccine not foreseen by the study protocol during the period starting one month before the application of the study vaccine and ending one month after that application. 11-Anu acute disease, moderate or severe, at the time of enrollment. 12-Do not approve a written examination about cholera.

Age minimum: 18 years
Age maximum: 40 years
Gender: Male

Health Condition(s) or Problem(s) studied

Cholera disease

Intervention(s)

The volunteers were randomly distributed in two parallel groups respectively, vaccine or placebo. In the vaccine group 15 volunteers were fed with a single oral dose of 10E9 CFU of a freshly harvested of the attenuated 638 strain V. cholerae O1 El Tor Ogawa candidate to cholera vaccine. This strain has been modified by engineering techniques to be nontoxinogenic (without CTX-hapA::celA), it was obtained at the National Center for Scientific Research, Cuba. In the placebo group 12 volunteers were fed with a suspension containing 1.33% of sodium bicarbonate alone. One month after vaccine or placebo administration, both groups were fed with a single oral dose of 10E5 CFU of a freshly harvested of the 3008 strain V. cholerae O1 El Tor Ogawa.

Primary Outcome(s)

Primary Objective: To assess the protective efficacy of the attenuated 638 strain in volunteers, by mean of a challenge study with a homologous biotype and serotype cholera virulent strain. Primary endpoints: 1-Incidence of diarrheas in both groups during the 5 days after virulent strain feeding

Secondary Outcome(s)

Secondary Objectives: 1-To assess the safety and reactogenicity of the attenuated 638 strain in volunteers during 5 days after immunization. 2-To assess mucosal and systemic immunogenicity of the attenuated 638 strain in volunteers during the trial. 3-To assess the immune response induced by the virulent strain in those volunteers whom were previously fed in the stage I, with the placebo and the attenuated 638 strain. 4-To identify and to quantify the attenuated and virulent strains excreted by volunteers 5 days before and 3 days after the antibiotic treatment. 5-To assess the dynamic of the immune response against Vibrio cholerae until 28 days after inoculation in both stages of the study. Secondary endpoints: Safety and Reactogenicity: 1-Incidence of expected adverse event grade 3 within 5 days after the attenuated 638 strain feeding. 2-Incidence of grade 3 diarrheas during the following 5 days after application of the attenuated 638 strain (Stage 1). 3-Incidence of diarrheas of any intensity during the following 5 days after application of the attenuated 638 strain (Stage 1). 4-Incidence of any other expected adverse events of intensity grade 3, in the same period of time. 5-Incidence of any other expected adverse events of whatever intensity, observed in the same period of time. 6-Incidence, intensity and relationship to the attenuated 638 strain administration of whatever unexpected adverse event during the whole trial. 7-Incidence, intensity and relationship to the attenuated 638 strain administration of any serious adverse event during the whole trial. 8-Incidence of clinical lab tests with pathologic values, 7 days after the attenuated 638 strain feeding. Immunogenicity: 1-Seroconversion of vibriocidal antibodies expressed as the increase of titer in sera in four or more time on day 14 in comparison with the preimmune titer. 2-Seroconversion of ELISA anti-Ogawa LPS IgA, IgM and IgG antibodies in sera expressed as the increase of titer in sera in two or more time on day 14 in comparison with the preimmune titer. 3-Determination of ELISA anti LPS IgA antibodies in saliva, expressed as twofold or more optical density (OD) units detected on day 9 in comparison with the preimmune units detected over 0.4. 4-Determination of specific IgA-antibodies shedding cells (ASC) to Owaga LPS by ELISPOT, expressed as the number of positive spots >= 1 per each 10E6 peripheral blood mononuclear cells.

Secondary ID(s)

Cólera002M

Source(s) of Monetary Support

Finlay Institute

Secondary Sponsor(s)

Centro Nacional de Investigaciones Científicas (CNIC) (Cuban National Center for Scientific Researches)