Clinical trial NCT00480714: A Study of the Immunogenicity of BCG, Delivered Intradermally in Healthy Volunteers
Official title: A Study of the Immunogenicity of M. Bovis BCG (SSI Strain), Delivered Intradermally in Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: TB
Keywords: TB
Vaccine
BCG
Lead sponsor: University of Oxford
Sponsor class: OTHER
First posted: 2007-05-31
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

Brief summary: To assess the immunogenicity of M. bovis BCG (SSI strain), given intrademally in the standard dose used in clinical practice and to measure the development of the immune response in the first six months after administration. M. bovis BCG is a fully licensed vaccine that has been in routine clinical use for the last 50 years. It is the most widely administered vaccine in the world today and has an excellent safety record.

Detailed description: Volunteers for the study will be recruited through advertisements. Each volunteer will have received an information sheet concerning the study and will have agreed to participate in writing.

Volunteers will be given at least 48 hours between reading the information leaflet and agreeing to participate. Female volunteers will have a pregnancy test prior to enrollment. Volunteers will give signed consent for their GP's to be notified about their participation in the trial. The GP will be faxed a letter on the day of screening and asked to reply if they know of a reason why the volunteer should not take part. The signed consent form will also be faxed with the letter.

A week after the screening visit and after a negative Heaf test, subjects will receive a single intradermal injection of 106 cfu M. bovis BCG in 0.1ml just inferior to the insertion of the deltoid muscle. Blood tests will be taken at the screening visit and day of immunisation, 1 and 2 weeks, and 1, 2, 3 and 6 months after the immunisation. 75mls will be taken on the screening visit, and 60mls will be taken on all subsequent visits. Screening samples will be tested for full blood count, biochemical screen and immunological assays to determine vaccine immunogenicity. Peripheral blood mononuclear cells will be prepared for cellular immunological assays to be performed without or following cryopreservation. Other serological measures of immune response, i.e.

antibody titres, will be assayed on frozen plasma samples. All blood tests will be taken within 1-3 days of the due date as described in the schedule above.

Eligibility criteria: Inclusion Criteria:

* Healthy adult aged 18-65 years.
* Normal medical history and physical examination.
* Normal urine dipstick, blood count, liver enzymes, and creatinine.

Exclusion Criteria:

* Exposure to TB/BCG vaccination at any point. Previous residence in a TB endemic area.
* Clinically significant history of skin disorder (eczema, psoriasis, etc.), allergy, immunodeficiency, cardiovascular disease, respiratory disease, endocrine disorder, liver disease, renal disease, gastrointestinal disease, neurological illness, psychiatric disorder, drug or alcohol abuse.
* Oral or systemic steroid medication or the use of immunosuppressive agents.
* Positive HIV or core HBV antibody test.
* Positive Heaf test
* Positive ANA or serum anti-DNA antibody.
* Confirmed pregnancy

Primary outcomes:
measure: The induction of T-cell responses
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Oxford
country: United Kingdom
facility: University of Oxford, CCVTM, Churchill Hospital
state: Oxfordshire
Study officials:
affiliation: University of Oxford
name: Helen I McShane
role: PRINCIPAL_INVESTIGATOR
References:
citation: McShane H, Pathan AA, Sander CR, Keating SM, Gilbert SC, Huygen K, Fletcher HA, Hill AV. Recombinant modified vaccinia virus Ankara expressing antigen 85A boosts BCG-primed and naturally acquired antimycobacterial immunity in humans. Nat Med. 2004 Nov;10(11):1240-4. doi: 10.1038/nm1128. Epub 2004 Oct 24.
citation: Pathan AA, Sander CR, Fletcher HA, Poulton I, Alder NC, Beveridge NE, Whelan KT, Hill AV, McShane H. Boosting BCG with recombinant modified vaccinia ankara expressing antigen 85A: different boosting intervals and implications for efficacy trials. PLoS One. 2007 Oct 24;2(10):e1052. doi: 10.1371/journal.pone.0001052.