BCG Revaccination Study in Diabetic and Non-Diabetic Adults

NCT06246851 | Active Not Recruiting DMC

• 1 other identifier: TB046
• Study Type: interventional
• Target: 36
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to:

1. 1.explore whether investigators can make BCG more effective by giving it in a different way. For this, aerosol inhaled BCG will be compared against the conventional BCG injection.
2. 2.explore if there are differences in response to re-vaccination in healthy volunteers with and without Type 2 Diabetes.

Conditions

Tuberculosis

Outcome Measures

Primary Outcomes (2)

• Intradermal vs. aerosol BCG in non-type 2 diabetics

  To compare the immunological response of BCG re-vaccination by the aerosol inhaled route to the intradermal route in healthy historically intradermally BCG-vaccinated volunteers. This will be measured using laboratory markers of innate and adaptive immunity, which may include ex-vivo ELISpot and ELISAs, RNA sequence analysis and intracellular cytokine staining of blood. This will also be measured using flow cytometry, ELISA and cytokine staining of BAL samples. This will be achieved by blood test done at each follow up visit and bronchoscopy to retrieve BAL sample at Day 14 visit for non- diabetic volunteers.

  Up to day 168

• Intradermal (in type 2 diabetics) vs intradermal (in non-type 2 diabetics)

  To compare the immunological response of BCG re-vaccination by the intradermal route in historically intradermally BCG-vaccinated volunteers with Type 2 Diabetes and non-diabetic healthy adults. This will be measured using laboratory markers of innate and adaptive immunity, which may include ex-vivo ELISPOT and ELISAs, RNA sequence analysis and intracellular cytokine staining of blood. This will be achieved through the blood test done at each follow up visit.

  Up to day 168

Secondary Outcomes (1)

• Intradermal or aerosol BCG re-vaccination safety in healthy volunteers

  Up to day 168

Other Outcomes (1)

• Examination of immunological and microbiological markers

  Up to day 168

Study Arms (3)

Group A: A1: 2-8 x 10^5 cfu or 1 x 10^5 cfu intradermal BCG (non-type 2 diabetic group)

EXPERIMENTAL

A1: 6 historically BCG-vaccinated volunteers without type 2 diabetes will receive 2-8 X 10\^5 cfu intradermally injected BCG. A2: 6 historically BCG-vaccinated volunteers without type 2 diabetes will receive 1 x 10\^5 cfu intradermally injected BCG. All Group A volunteers will have a bronchoscopy 14 days post challenge.

Biological: BCG Danish

Group B: 2-8 x 10^6 cfu or 1 x 10^6 cfu aerosol inhaled BCG (non-type 2 diabetic group)

EXPERIMENTAL

B1: 6 historically BCG-vaccinated volunteers without type 2 diabetes will receive 2-8 X 10\^6 cfu aerosol inhaled BCG. B2: 6 historically BCG-vaccinated volunteers without type 2 diabetes will receive 1 X 10\^6 cfu aerosol inhaled BCG. All Group B volunteers will have a bronchoscopy 14 days post challenge.

Biological: BCG Danish

Group C: 2-8 x 10^5 cfu or 1 x 10^5 cfu intradermal BCG (type 2 diabetic group)

EXPERIMENTAL

C1: 6 historically BCG-vaccinated volunteers with confirmed type 2 diabetes will receive 2-8 X 10\^5 cfu intradermally injected BCG. C2: 6 historically BCG-vaccinated volunteers with confirmed type 2 diabetes will receive 1 X 10\^5 cfu intradermally injected BCG. All Group C volunteers will not have a bronchoscopy.

Biological: BCG Danish

Interventions

BCG Danish BIOLOGICAL

BCG Danish 1331 is on the WHO list of pre-qualified vaccines and has a well-defined side effect profile. BCG is licensed for delivery via the intradermal route. It is not licensed for delivery via the aerosol route.

Group A: A1: 2-8 x 10^5 cfu or 1 x 10^5 cfu intradermal BCG (non-type 2 diabetic group); Group B: 2-8 x 10^6 cfu or 1 x 10^6 cfu aerosol inhaled BCG (non-type 2 diabetic group); Group C: 2-8 x 10^5 cfu or 1 x 10^5 cfu intradermal BCG (type 2 diabetic group)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy adults aged 18-65 years
• Resident in or near Oxford for the duration of the study period
• Provide written informed consent
• Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner (or review summary care record, if available)
• Allow the investigator to register volunteer details with a confidential database (The Over- volunteering Protection Service) to prevent concurrent entry into clinical studies/trials
• Agreement to refrain from blood donation during the course of the study
• For persons of child-bearing potential (POCBP) only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening, vaccination and bronchoscopy
• Able and willing (in the investigator's opinion) to comply with all study requirements
• No clinically relevant findings on physical examination
• Screening IGRA negative
• Willing to be tested for evidence of SARS-CoV-2 infection and to allow public health notification of the results if required
• Previously vaccinated with the BCG (at least 12 months prior to enrolment, as evidenced by a visible scar or documentation in medical or occupational health records)
• Group C only - Documented diagnosis of T2DM (made at least 12 months prior to enrolment) initiated on a management plan with medication including use of metformin

You may not qualify if:

• Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment or during the trial follow up period
• History of anaphylaxis to vaccination or any allergy likely to be exacerbated by any component of the study agent, any essential study procedure, sedative drugs, or any local or general anaesthetic agents
• Clinically significant history of skin disorder, allergy, atopy, cancer (except BCC of the skin or CIS of the cervix), bleeding disorder, cardiovascular disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder (excluding T2DM in Group C only), neurological illness, psychiatric disorder, drug or alcohol abuse
• Any significant autoimmune conditions or immunodeficiency (including HIV)
• Previous diagnosis or treatment for TB disease or latent TB infections
• Clinical, radiological, or laboratory evidence of current active TB disease or latent TB infection
• Previous receipt of any investigational TB vaccine or aerosolised BCG
• More than one previous BCG vaccination
• Positive HBsAg, HCV or HIV antibodies
• Concurrent use of oral, inhaled or systemic steroid medication or use for more than 14 days within the last 6 months (steroids used as a cream or ointment are permissible), or the use of other immunosuppressive agents concurrently or for more than 14 days within the last 6 months
• Administration of immunoglobulins and/or any blood products within the three months preceding the planned study vaccination date
• Administration of a live vaccine within the preceding 28 days prior to enrolment
• Administration of any other non-live vaccine within the preceding 14 days prior to enrolment
• Pregnancy, lactation or intention to become pregnant during study period
• Previously resident for more than 12 months concurrently in the rural areas of a tropical climate where significant non-tuberculous mycobacterial exposure is likely

Sponsors & Collaborators

• University of Oxford: lead

Study Sites (1)

Centre for Clinical Vaccinology and Tropical Medicine

Oxford, Oxfordshire, OX3 7LE, United Kingdom

Location

MeSH Terms

Conditions

Tuberculosis

Condition Hierarchy (Ancestors)

Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Study Officials

• Helen McShane, Professor

  University of Oxford

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a phase 1 study exploring differences between the immunological responses to revaccination with intradermal-BCG and aerosol-inhaled BCG in healthy adults and those with pre-existing T2DM. There will be three study groups with twelve volunteers in each group. Volunteers will be enrolled into groups based upon whether they have a diagnosis of T2DM. They will then be vaccinated with intradermal BCG (Groups A and C) or aerosolised BCG (Group B).

Study Record Dates

• First Submitted: December 19, 2023
• First Posted: February 7, 2024
• Study Start: April 3, 2024
• Primary Completion (Estimated): August 31, 2028
• Study Completion (Estimated): August 31, 2028
• Last Updated: April 24, 2026

Record last verified: 2026-04

Locations

GB (1)