Human Innate Immune Responses To Mycobacterial Aerodigestive Tract Infection

NCT01074775 | Completed

• 1 other identifier: UBC-INNATE01
• Study Type: interventional
• Target: 7
• Locations: 1 country
• Sites: 1

Brief Summary

The approach we will use is to employ measurement of the activation of white blood cells, to look at patterns of responses during a controlled infection of the gut with Mycobacterium bovis. M. bovis can be conveniently obtained in a safe and pure form as an oral vaccine. By giving three challenges of M bovis to the gut, we will simulate repeated gut infections with this organism. We can then compare the activation of cells in the blood to the immune responses seen after each challenge, to determine whether the non-specific defences of the gut can block each subsequent infection.

Conditions

Bacterial Infections

Keywords

innate immunity; mycobacterium bovis; mucosal immunity; adaptive immunity; genomics

Outcome Measures

Primary Outcomes (1)

• Genomics profile

  Peripheral blood mononuclear cell gene expression measured by analysis of extracted mRNA using polymerase chain reaction

  12 months (23 visits)

Secondary Outcomes (1)

• Cell mediated immune responses

  12 months (8 visits)

Study Arms (1)

Challenge group

EXPERIMENTAL

Recipients of three challenge infections with oral M bovis

Biological: Gut infection challenge with M bovis

Interventions

Gut infection challenge with M bovis BIOLOGICAL

Oral delivery of 100mg viable M bovis (approximately 10,000,000 viable bacilli) in 5mL 1.5% sodium glutamate solution on three occasions on days 0, 28 and 49

Also known as: Bacille Calmette Guerin "Moreau Rio de Janeiro"

Challenge group

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Adult volunteers, 18 to 45 years of age, who sign an informed consent form following a detailed explanation of participation in the protocol.
• Volunteers who are in good health as determined by medical history, physical examination and clinical judgement.
• Volunteers who will be available for the duration of the study.
• Volunteers willing and able to give written informed consent.

You may not qualify if:

• Volunteers who are contraindicated for BCG vaccination according to the Manufacturer's Data Sheet.
• Individuals who have hypersensitivity to any component of the vaccine used in this study.
• Individuals who have severe or multiple allergies, including to drugs or pharmaceutical agents.
• Volunteers who are receiving drug treatment for, or who have a significant history of, cardiological or respiratory disease. Volunteers who are suffering from severe cardio-respiratory disease, including hypertension, or an active neurological disorder.
• Individuals found to be HIV antibody positive at screening, or with a known impairment of immune function, or those receiving immunosuppressive therapy, including regular inhaled steroids. Intermittent steroid use (less than twice per month in the preceding 3 months) is acceptable.
• Individuals with acute infections (including fever \>38°C).
• Women who are pregnant or lactating.
• Women capable of becoming pregnant who do not agree to have pregnancy testing before immunisation, and/or who do not agree to take effective contraception for the duration of the study period.
• Individuals with a current problem with substance abuse or with a history of substance abuse, which, in the opinion of the investigator, might interfere with participation in the study.
• Individuals with any condition, which, in the opinion of the investigator, might interfere with the evaluation with the study objectives.
• Individuals who have received an investigational agent within 30 days prior to entry, or been in any other study in the last 6 months.
• Individuals who are planning to leave the area of the study site prior to the end of the study period, or who are likely not to complete the study.

Sponsors & Collaborators

• St George's, University of London: lead
• University of British Columbia: collaborator
• Wellcome Trust: collaborator
• Fundação Ataulpho de Paiva, Rio de Janeiro, Brasil: collaborator
• Foundation for the National Institutes of Health: collaborator
• Bill and Melinda Gates Foundation: collaborator

Study Sites (1)

St George's Vaccine Institute, St George's University of London

London, England, SW17 0RE, United Kingdom

Location

Related Links

• St George's Vaccine Institute website
• St George's - University of London website

MeSH Terms

Conditions

Bacterial Infections

Condition Hierarchy (Ancestors)

Bacterial Infections and Mycoses; Infections

Study Officials

• David JM Lewis, MD

  St George's - University of London, UK

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: February 23, 2010
• First Posted: February 24, 2010
• Study Start: September 1, 2006
• Primary Completion: September 1, 2007
• Study Completion: September 1, 2007
• Last Updated: February 24, 2010

Record last verified: 2010-02

Locations

GB (1)