Antibiotics and Vaccine Immune Responses Study

NCT ID: NCT06148025

Last Updated: 2025-12-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE4

Total Enrollment

348 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-11-23

Study Completion Date

2028-10-01

Brief Summary

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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?

Detailed Description

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The study is divided into two sub-studies. The first sub-study (BCG re-challenge) is an experimental medicine study in 168 healthy participants to determine if depletion of the gut microbiota leads to impaired BCG-induced protection against a subsequent Mycobacterium bovis BCG intradermal challenge.

The second sub-study (Yellow Fever vaccine) has a very similar experimental design to the first but will determine if depletion of the gut microbiota leads to impaired BCG-induced protection against other infections. To assess this, participants in this sub-study (n=180) will be re-challenged after 3 months with a live attenuated viral vaccine, the Yellow Fever vaccine, which induces a mild viremia.

In both sub-studies, participants will initially be randomised to receive a 3 day course of antibiotics or none (comparator group). The two groups in each sub-study will be randomised again to receive either BCG vaccine or 0.9% NaCl placebo injection in the left arm.

BCG re-challenge sub-study (Sub-study 1): Six months following randomisation, all participants will receive a BCG vaccine challenge in the right arm. A punch skin biopsy will be taken of this challenge site 2 weeks after the challenge to assess M. bovis BCG bacterial load in the skin.

Yellow Fever vaccine sub-study (Sub-study 2): Three months following randomisation, all participants will receive a Yellow Fever vaccine challenge in the right arm. Blood samples will be collected from Yellow Fever vaccinated participants at day 3, 5 and 7 following Yellow Fever vaccine challenge to quantify Yellow Fever viral load in blood.

All participants in both sub-studies will have blood samples collected at randomisation, before each vaccination, 2 weeks after each BCG vaccination and in the Yellow Fever vaccine sub-study at day 3, 5 and 7 following Yellow Fever vaccination. Stool samples will be collected prior to randomisation, and prior to each vaccination.

Conditions

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Vaccine Response Impaired

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Participants are allocated to Substudy 1 (BCG re-challenge) or Substudy 2 (Yellow Fever vaccine) Participants are randomised to receive

* antibiotics or comparator (unblinded) and
* BCG vaccine or placebo (blinded)
* BCG vaccine or Yellow Fever vaccine (unblinded)
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators
Participants and Investigator are blinded to BCG vaccine or placebo.

Study Groups

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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

Group Type EXPERIMENTAL

Yellow Fever vaccine

Intervention Type BIOLOGICAL

0.5ml injected subcutaneously

Vancomycin Oral Capsule

Intervention Type DRUG

500mg every 6 hours for 3 days

Neomycin Oral Product

Intervention Type DRUG

1000mg every 6 hours for 3 days

Metoclopramide (Maxolon)

Intervention Type DRUG

10mg every 8 hours

Loperamide HCl

Intervention Type DRUG

2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day

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

Group Type EXPERIMENTAL

Yellow Fever vaccine

Intervention Type BIOLOGICAL

0.5ml injected subcutaneously

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

Group Type EXPERIMENTAL

BCG vaccine

Intervention Type BIOLOGICAL

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

Vancomycin Oral Capsule

Intervention Type DRUG

500mg every 6 hours for 3 days

Neomycin Oral Product

Intervention Type DRUG

1000mg every 6 hours for 3 days

Metoclopramide (Maxolon)

Intervention Type DRUG

10mg every 8 hours

Loperamide HCl

Intervention Type DRUG

2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day

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

Group Type EXPERIMENTAL

BCG vaccine

Intervention Type BIOLOGICAL

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

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

Group Type EXPERIMENTAL

BCG vaccine

Intervention Type BIOLOGICAL

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

Vancomycin Oral Capsule

Intervention Type DRUG

500mg every 6 hours for 3 days

Neomycin Oral Product

Intervention Type DRUG

1000mg every 6 hours for 3 days

Metoclopramide (Maxolon)

Intervention Type DRUG

10mg every 8 hours

Loperamide HCl

Intervention Type DRUG

2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day

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

Group Type EXPERIMENTAL

BCG vaccine

Intervention Type BIOLOGICAL

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

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

Group Type EXPERIMENTAL

BCG vaccine

Intervention Type BIOLOGICAL

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

Yellow Fever vaccine

Intervention Type BIOLOGICAL

0.5ml injected subcutaneously

Vancomycin Oral Capsule

Intervention Type DRUG

500mg every 6 hours for 3 days

Neomycin Oral Product

Intervention Type DRUG

1000mg every 6 hours for 3 days

Metoclopramide (Maxolon)

Intervention Type DRUG

10mg every 8 hours

Loperamide HCl

Intervention Type DRUG

2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day

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

Group Type EXPERIMENTAL

BCG vaccine

Intervention Type BIOLOGICAL

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

Yellow Fever vaccine

Intervention Type BIOLOGICAL

0.5ml injected subcutaneously

Interventions

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BCG vaccine

0.1ml injected intradermally over the distal insertion of the deltoid muscle onto the humerus

Intervention Type BIOLOGICAL

Yellow Fever vaccine

0.5ml injected subcutaneously

Intervention Type BIOLOGICAL

Vancomycin Oral Capsule

500mg every 6 hours for 3 days

Intervention Type DRUG

Neomycin Oral Product

1000mg every 6 hours for 3 days

Intervention Type DRUG

Metoclopramide (Maxolon)

10mg every 8 hours

Intervention Type DRUG

Loperamide HCl

2mg tablets/capsules: 2 tablets/capsules initially, followed by 1 tablet after each loose motion, to a maximum of 8 tablets/capsules per day

Intervention Type DRUG

Other Intervention Names

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Firvanq Vancocin HCl Pulvules Neo-Fradin

Eligibility Criteria

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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)

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 or antibiotics
* 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)
Minimum Eligible Age

18 Years

Maximum Eligible Age

35 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Royal Adelaide Hospital

OTHER

Sponsor Role collaborator

Flinders University

OTHER

Sponsor Role collaborator

University of Sydney

OTHER

Sponsor Role collaborator

Telethon Kids Institute

OTHER

Sponsor Role collaborator

Centenary Institute

UNKNOWN

Sponsor Role collaborator

South Australian Health and Medical Research Institute

OTHER

Sponsor Role lead

Responsible Party

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David Lynn

Director, Computational & Systems Biology Program

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Simone Barry

Role: PRINCIPAL_INVESTIGATOR

Royal Adelaide Hospital

David Lynn

Role: PRINCIPAL_INVESTIGATOR

South Australian Health and Medical Research Institute

Locations

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South Australian Health and Medical Research Institute

Adelaide, South Australia, Australia

Site Status RECRUITING

Countries

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Australia

Central Contacts

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David Lynn

Role: CONTACT

+61 8 8128 4053

Facility Contacts

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David Lynn

Role: primary

+61 8 8128 4053

Other Identifiers

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2023/HREC00066

Identifier Type: -

Identifier Source: org_study_id

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