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Trial details imported from ClinicalTrials.gov
For full trial details, please see the original record at
https://clinicaltrials.gov/ct2/show/NCT06148025
Registration number
NCT06148025
Ethics application status
Date submitted
29/09/2023
Date registered
28/11/2023
Date last updated
4/04/2024
Titles & IDs
Public title
Antibiotics and Vaccine Immune Responses Study
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Scientific title
A Human Experimental Medicine Study to Assess Whether the Gut Microbiota Regulates Specific and Non-specific Immune Responses to Vaccination
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Secondary ID [1]
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2023/HREC00066
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Universal Trial Number (UTN)
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Trial acronym
AVIRS
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Linked study record
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Health condition
Health condition(s) or problem(s) studied:
Vaccine Response Impaired
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Condition category
Condition code
Intervention/exposure
Study type
Interventional
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Description of intervention(s) / exposure
Other interventions - BCG vaccine
Other interventions - Yellow Fever vaccine
Treatment: Drugs - Vancomycin Oral Capsule
Treatment: Drugs - Neomycin Oral Product
Experimental: Substudy 1 - BCG vaccine, antibiotics and 2nd BCG vaccine - Randomised to receive antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later
Experimental: Substudy 1 - BCG vaccine, no antibiotics and 2nd BCG vaccine - Randomised to receive no antibiotics and a BCG vaccine at visit 1 and a second BCG vaccine 6 months later
Experimental: Substudy 1 - BCG vaccine, antibiotics and placebo vaccine - Randomised to receive antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later
Experimental: Substudy 1 - BCG vaccine, no antibiotics and placebo vaccine - Randomised to receive no antibiotics, a placebo vaccine at visit 1 and a BCG vaccine 6 months later
Experimental: Substudy 2 - Yellow Fever vaccine, antibiotics and BCG vaccine - Randomised to receive antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later
Experimental: Substudy 2 - Yellow Fever vaccine, no antibiotics and BCG vaccine - Randomised to receive no antibiotics, a BCG vaccine at visit 1 and a Yellow Fever vaccine 3 months later
Experimental: Substudy 2 - Yellow Fever vaccine, antibiotics and placebo vaccine - Randomised to receive antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later
Experimental: Substudy 2 - Yellow Fever vaccine, no antibiotics and placebo vaccine - Randomised to receive no antibiotics, a placebo vaccine at visit 1 and a Yellow Fever vaccine 3 months later
Other interventions: BCG vaccine
0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus
Other interventions: Yellow Fever vaccine
0.5ml injected subcutaneously
Treatment: Drugs: Vancomycin Oral Capsule
500mg every 6 hours for 3 days
Treatment: Drugs: Neomycin Oral Product
1000mg every 6 hours for 3 days
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Intervention code [1]
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Other interventions
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Intervention code [2]
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Treatment: Drugs
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Comparator / control treatment
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Control group
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Outcomes
Primary outcome [1]
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Sub-study 1 BCG re-challenge
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Assessment method [1]
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Mycobacterial load (Colony Forming Units (CFU)) in the skin biopsy site in BCG-vaccinated participants not exposed to antibiotics (BCG-No ABX) compared to BCG-vaccinated participants that were exposed to antibiotics (BCG-ABX)
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Timepoint [1]
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5 years
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Primary outcome [2]
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Sub-study 2 Yellow Fever vaccine
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Assessment method [2]
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Yellow Fever viremia (viral copies/ml blood) at D3-7 post YF vaccination in BCG-vaccinated participants not exposed to antibiotics (BCG-No ABX) compared to BCG-vaccinated participants that were exposed to antibiotics (BCG-ABX)
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Timepoint [2]
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5 years
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Secondary outcome [1]
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Sub-study 1 - Bacterial load
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Assessment method [1]
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Day 0 bacterial load (16S copies/g stool) in all ABX participants vs No-ABX participants
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Timepoint [1]
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5 years
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Secondary outcome [2]
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Sub-study 2 - Bacterial load
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Assessment method [2]
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Day 0 bacterial load (16S copies/g stool) in all ABX participants vs No-ABX participants
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Timepoint [2]
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5 years
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Secondary outcome [3]
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Sub-study 1 - Microbiota diversity
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Assessment method [3]
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Day 0 microbiota diversity (Shannon diversity index) in all ABX participants vs No-ABX participants
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Timepoint [3]
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5 years
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Secondary outcome [4]
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Sub-study 2 - Microbiota diversity
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Assessment method [4]
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Day 0 microbiota diversity (Shannon diversity index) in all ABX participants vs No-ABX participants
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Timepoint [4]
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5 years
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Secondary outcome [5]
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Sub-study 1 - Mycobacterial load
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Assessment method [5]
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Mycobacterial load (CFU) in the skin biopsy site in BCG-vaccinated participants compared to placebo-vaccinated participants
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Timepoint [5]
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5 years
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Secondary outcome [6]
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Sub-study 1 - Mycobacterial IFN? responses
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Assessment method [6]
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IFN? production in pg/mL following stimulation of PBMC with mycobacteria in BCG-ABX participants versus BCG-No ABX participants
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Timepoint [6]
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5 years
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Secondary outcome [7]
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Sub-study 1 - Mycobacterial T cell activation marker responses
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Assessment method [7]
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% of CD69+CD137+ CD4 T cells following stimulation of PBMC with mycobacteria in BCG-ABX participants versus BCG-No ABX participants
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Timepoint [7]
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5 years
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Secondary outcome [8]
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Sub-study 2 - Peak viraemia
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Assessment method [8]
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Peak viraemia (viral copies/ml blood) at D3-7 post YF vaccination in BCG-vaccinated participants compared to placebo-vaccinated participants
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Timepoint [8]
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5 years
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Secondary outcome [9]
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Sub-study 2 - Heterologous TNFa responses following R848 stimulation
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Assessment method [9]
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D90 PBMC TNFa responses (pg/mL) following in vitro stimulation with viral ligand R848 in BCG-ABX participants versus BCG-No ABX participants
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Timepoint [9]
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5 years
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Secondary outcome [10]
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Sub-study 2 - Heterologous TNFa responses following LPS stimulation
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Assessment method [10]
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D90 PBMC TNFa responses (pg/mL) following in vitro stimulation with bacterial ligand LPS in BCG-ABX participants versus BCG-No ABX participants
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Timepoint [10]
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5 years
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Secondary outcome [11]
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Sub-study 2 - Heterologous TNFa responses following fungal stimulation
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Assessment method [11]
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D90 PBMC TNFa responses (pg/mL) following in vitro stimulation with fungal ligand heat-killed C. albicans in BCG-ABX participants versus BCG-No ABX participant
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Timepoint [11]
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5 years
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Eligibility
Key inclusion criteria
- 18-35 years old
- Provided a signed and dated informed consent form
- BCG naïve (Arm 1) and BCG and YF vaccine naïve (Arm 2)
- Willing to take short antibiotic course
- Willing to undergo a punch biopsy (Arm 1)
- Willing to have up to 7 blood samples and 3 stool samples collected over 5-7 months
- Not pregnant or intending to get pregnant for the duration of the study (a pregnancy
test will be offered to females)
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Minimum age
18
Years
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Maximum age
35
Years
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Sex
Both males and females
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Can healthy volunteers participate?
Yes
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Key exclusion criteria
- Previous BCG or YF vaccination
- Previous YF infection
- Evidence of latent TB infection (LTBI) (assessed through a questionnaire) (IGRA to
confirm if needed)
- People with contraindications for BCG vaccination:
- malignancies involving bone marrow or lymphoid systems, primary or secondary
immunodeficiencies, HIV infection
- moderate/severe skin disease including eczema, dermatitis or psoriasis
- requiring immunosuppressive drugs or other immune modifying drugs e.g.
corticosteroids, non-biological immunosuppressants, biological agents (such as
monoclonal antibodies against tumour necrosis factor (TNF)-alpha)
- People with contraindications to YF vaccination:
- History of thymus disease, including myasthenia gravis, thymoma, thymectomy,
DiGeorge syndrome, thymic damage from chemoradiotherapy or graft-versus-host
disease
- YF vaccination is contraindicated in immunocompromised individuals, including
individuals who have HIV infection, primary immunodeficiencies (including
inherited IFNAR1 deficiency), or are taking corticosteroids or other
immunosuppressive agents and haematopoietic stem cell transplant recipients
- People who have had a haematopoietic stem cell transplant
- Individuals with history of severe allergic reactions to egg or chicken proteins
- Pregnant or breastfeeding or planning to become pregnant
- History of renal disease/insufficiency
- Tattoo obscuring BCG vaccination site(s)
- Any history of severe allergic reaction or anaphylaxis to vaccination
- People with chronic serious underlying illness
- Have received any prescribed oral or intravenous antibiotic in the 28 days prior to
study visits 1 and 4 (including isoniazid, rifampicin, streptomycin and ethambutol as
these particular antibiotics have activity against M. bovis)
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Study design
Purpose of the study
Basic Science
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Allocation to intervention
Randomised controlled trial
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Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
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Methods used to generate the sequence in which subjects will be randomised (sequence generation)
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Masking / blinding
Blinded (masking used)
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Who is / are masked / blinded?
The people receiving the treatment/s
The people analysing the results/data
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Intervention assignment
Parallel
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Other design features
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Phase
Phase 4
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Type of endpoint/s
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Statistical methods / analysis
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Recruitment
Recruitment status
Recruiting
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Data analysis
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Reason for early stopping/withdrawal
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Other reasons
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Date of first participant enrolment
Anticipated
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Actual
23/11/2023
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Date of last participant enrolment
Anticipated
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Actual
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Date of last data collection
Anticipated
1/10/2028
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Actual
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Sample size
Target
348
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Accrual to date
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Final
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Recruitment in Australia
Recruitment state(s)
SA
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Recruitment hospital [1]
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South Australian Health and Medical Research Institute - Adelaide
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Recruitment postcode(s) [1]
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5000 - Adelaide
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Funding & Sponsors
Primary sponsor type
Other
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Name
South Australian Health and Medical Research Institute
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Address
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Country
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Other collaborator category [1]
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Other
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Name [1]
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Royal Adelaide Hospital
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Address [1]
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Country [1]
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Other collaborator category [2]
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Other
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Name [2]
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Flinders University
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Address [2]
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Country [2]
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Other collaborator category [3]
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Other
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Name [3]
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University of Sydney
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Address [3]
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Country [3]
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Other collaborator category [4]
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Other
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Name [4]
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Telethon Kids Institute
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Address [4]
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Country [4]
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Other collaborator category [5]
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Other
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Name [5]
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Centenary Institute of Cancer Medicine and Cell Biology
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Address [5]
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Country [5]
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Ethics approval
Ethics application status
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Summary
Brief summary
The goal of this clinical trial is to examine immune responses to the BCG vaccine in healthy
adults who have, or who have not, taken antibiotics to deplete their gut bacteria prior to
vaccination.
The main question it aims to answer is: does depletion of the gut microbiota lead to impaired
BCG-induced protection against specific and non-specific to challenges to the immune system?
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Trial website
https://clinicaltrials.gov/ct2/show/NCT06148025
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Trial related presentations / publications
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Public notes
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Contacts
Principal investigator
Name
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Simone Barry
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Address
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Royal Adelaide Hospital
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Country
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Phone
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Fax
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Email
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Contact person for public queries
Name
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David Lynn
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Address
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Country
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Phone
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+61 8 8128 4053
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Fax
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Email
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[email protected]
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Contact person for scientific queries
Summary Results
For IPD and results data, please see
https://clinicaltrials.gov/ct2/show/NCT06148025
Download to PDF