Human challenge with Bordetella pertussis and delayed antibiotic treatment

A Human Controlled Infection Study to Establish Safety of Infection With Bordetella Pertussis With Antibiotic Therapy Delayed for up to 6 Weeks

This study is testing how safe it is to give healthy volunteers a mild whooping cough infection and then treat them with antibiotics to see how the bacteria behave and how the body responds.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 72 (estimated)
• Ages: 18 Years to 55 Years
• Sex: All
• Sponsor: University of Southampton (Academic / other)
• Locations: 1 site (Southampton, Hampshire)
• Trial ID: NCT05847322 on ClinicalTrials.gov

What this trial studies

This study aims to evaluate the safety of nasal inoculation of healthy volunteers with Bordetella pertussis, the bacterium that causes whooping cough, while administering antibiotic therapy to eradicate the infection after six weeks or upon symptom onset. The study will also investigate the natural clearance rate of the bacteria, the density of colonization, and the immune responses generated during the infection. Participants will be closely monitored, and those who exhibit symptoms will receive early treatment. The goal is to better understand the dynamics of pertussis colonization and its transmission.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 18 to 55 who can comply with study protocols and infection control measures.

Not a fit: Patients living in institutional settings or those with close contact to vulnerable individuals may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved strategies for managing and preventing whooping cough infections.

How similar studies have performed: While this approach is novel, previous studies have explored similar human challenge methodologies with varying degrees of success.

Eligibility criteria

Inclusion Criteria:

* Healthy adults aged 18 to 55 years inclusive on the day of screening
* Fully conversant in the English language
* Able to communicate easily by both mobile telephone, email and text messaging
* Able and willing (in the investigator's opinion) to comply with all study requirements
* Written informed consent to participate in the study
* Willingness to take a curative antibiotic regimen if / when required according to the study protocol
* Willingness to abide by infection control guidelines during social contact for the duration of their participation in the study
* Willingness to attend to the National Institute for Health Research (NIHR) Clinical Research Facility (CRF) Southampton immediately if they become symptomatic
* Agreement to have no bedroom contacts other than their corresponding contact/challenge volunteer between inoculation and 6 weeks after inoculation
* Able to answer all questions on the pre-consent questionnaire correctly

Exclusion Criteria:

* Individuals living in the same households as:

  1. unimmunised or partially immunised children and infants aged \< 1 year
  2. pregnant women \>32 weeks who have not received pertussis vaccination at least a week prior to contact
  3. immunosuppressed individuals
  4. frail individuals
  5. healthcare workers regularly working with vulnerable individuals as above
* Individuals who have inviolable commitments within the study period (from day 0 to week 6 + 2 days) to be in close contact with:

  1. unimmunised or partially immunised children and infants aged \< 1 year
  2. pregnant women \>32 weeks who have not received pertussis vaccination at least a week prior to contact
  3. immunosuppressed individuals
  4. frail individuals
* Individuals who live in a boarding school or dormitory during the study.
* B. pertussis detected on nasal wash taken before the initial challenge
* Individuals with a confirmed or suspected infection at the time of inoculation with B. pertussis
* Individuals who have participated in other interventional clinical trials in the last 12 weeks
* Individuals who have a history of receiving B. pertussis vaccination in the last 5 years
* Individuals who have previously participated in a B. pertussis human challenge study
* Individuals who have had a proven B. pertussis infection in the last 5 years
* Individuals who have a history of never being vaccinated against B. pertussis
* Current smokers defined as having had a cigarette/cigar in the last week (including vaping)
* Use of systemic antibiotics within 30 days of or during the challenge
* Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)
* Use of immunoglobulins or blood products within 3 months prior to enrolment
* History of allergic disease or reactions likely to be exacerbated by any component of the inoculum
* Contraindications to the use of azithromycin or macrolides
* Pregnancy, lactation or intention to become pregnant during the study
* Any clinically significant abnormal finding on biochemistry, haematology, toxicology or serological blood tests, urinalysis (see The following reference ranges are provided for the purpose of guidance only. Results that fall outside of these ranges may not be of clinical significance but should be considered on an individual basis.) or clinical examination - in the event of abnormal test results, confirmatory repeat tests will be requested
* Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data, for example recent surgery to the nasopharynx

Exclusion criteria - Contact volunteers

* Individuals living in the same households as:

  1. unimmunised or partially immunised children and infants aged \< 1 year
  2. pregnant women
  3. immunosuppressed individuals
  4. frail individuals
  5. healthcare workers working with vulnerable individuals as above
* Individuals who have inviolable commitments within the study period (from day 0 to week 6 + 2 days) to be in close contact with:

  1. unimmunised or partially immunised children and infants aged \< 1 year
  2. pregnant women \>32 weeks who have not received pertussis vaccination at least a week prior to contact
  3. immunosuppressed individuals
  4. frail individuals
* Individuals who have been involved in other clinical trials involving receipt of an investigational product over the last 12 weeks or if there is planned use of an investigational product during the study period
* Individuals who have previously participated in a B. pertussis human challenge study
* Individuals who have a history of never being vaccinated against B. pertussis
* Any confirmed or suspected immunosuppressive or immune-deficient state, including HIV infection; malignancy, asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (topical steroids are allowed)
* Contraindications to the use of azithromycin or macrolides
* Any clinically significant abnormal finding on clinical examination
* Any other significant disease, disorder, or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
* Pregnancy, lactation or intention to become pregnant during the study

Where this trial is running

Southampton, Hampshire

• NIHR Clinical Research Facility — Southampton, Hampshire, United Kingdom (Recruiting)

Study contacts

• Study coordinator: Robert Read

Conditions Pertussis/Whooping Cough