Meningitis, BacterialLac5-NasalNCT04135053
A Controlled Study to Assess Safety, Colonisation and Immunogenicity of Reconstituted Lyophilised Neisseria Lactamica
A study testing Lyophilised Neisseria lactamica in people with Meningitis, Bacterial, run by University of Southampton at 1 site in United Kingdom.
Trial summary
This study is part of a series of projects to develop and test new vaccines for meningitis. Previously researchers have given nose drops containing N. lactamica to over 350 volunteers, and shown that many of them (35-60%) can become colonised with N. Read more about this study
- Who is it for?
- Ages 18 to 45 yearsHealthy volunteers can take part
- Conditions the study is for
- Meningitis, Bacterial
- What is being tested?
- Lyophilised Neisseria lactamica
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 35 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Feb 2019to 31 Dec 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- Healthy adults aged 18 to 45 years inclusive on the day of enrolment
- Fully conversant in the English language
- Able and willing (in the investigator's opinion) to comply with all study requirements
- Provide written informed consent to participate in the trial
- For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and inoculation
- TOPS registration completed and no conflict found
Who cannot join
- Current active smokers defined as having smoked a cigarette or cigar in the last four weeks
- N. lactamica or N. meningitidis detected on throat swab or nasal wash taken at screening
- Individuals who have a current infection at the time of inoculation
- 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 been involved in clinical trials investigating meningococcal vaccines or experimental challenge with N. lactamica
- Use of systemic antibiotics within the period 30 days prior to the challenge
Show all 14Show fewer
- 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, specifically soya.
- Contraindications to the use of ciprofloxacin, specifically a history of epilepsy, prolonged QT interval, hypersensitivity to quinolones or a history of tendon disorders related to quinolone use
- Any clinically significant abnormal finding on clinical examination or screening investigations
- 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
- Occupational, household or intimate contact with immunosuppressed persons
- Pregnancy or lactation
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
NIHR Southampton Clinical Research Facility
Southampton
UHS.recruitmentCRF@nhs.net
About this study
Official title: A Human Controlled Infection Study to Assess Safety, Colonisation and Immunogenicity Following Nasal Inoculation With Reconstituted Lyophilised Wild Type Neisseria Lactamica
This study is part of a series of projects to develop and test new vaccines for meningitis. Previously researchers have given nose drops containing N. lactamica to over 350 volunteers, and shown that many of them (35-60%) can become colonised with N. lactamica and become resistant to becoming colonised with N.meningitidis without causing any illness or disease. In the future the study team would like to find out how N.lactamica helps children resist N.meningitidis, and develop new vaccines that exploit that mechanism.
Read the detailed description
In this pilot research, the research team will develop and validate a modification of the methodology previously used in another UK-based human challenge experiments. The research to be conducted in this study will inform the study team whether intranasal inoculation of reconstituted lyophilised Nlac (hereafter, lyoNlac), can result in immunising colonisation of participants and the optimal dose to achieve this.
Previous challenges have been conducted using frozen stocks of Nlac but this is relatively unsatisfactory because of instability of frozen stocks, and will not be practical in Mali. The facility to reconstitute dry powdered lyoNlac into water and inoculate as a nose drop will greatly simplify the experimental method. However, it is not known whether lyoNlac can be inoculated directly into volunteers and induce successful colonisation.
In summary this is a pilot study of the safety, efficacy and immunogenicity of the intranasal inoculation of healthy human volunteers with lyoNlac. This study will determine the efficacy of lyoNlac as an agent for inducing nasopharyngeal colonisation with this organism, which is an important methodological development for ease of administration of Nlac in experimental human challenge studies. The study team will aim to determine the dose of inoculum required to induce colonisation in 80% of volunteers (the Standard Inoculum or SI). This SI will be used in future studies aiming to optimise duration of colonisation and immunogenicity induced by lyoNlac.
- Conditions
- Meningitis, Bacterial
- Being tested
- Lyophilised Neisseria lactamica
- Keywords
- meningitis, healthy volunteer
- Medical subject headings
- Meningitis, Bacterial, Meningitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Lyophilised Neisseria lactamicaBiological
Previously lyophilised Neisseria lactamica will be reconstituted and intranasally given to participants
| Study group | Role | What they receive |
|---|---|---|
| Challenge | Experimental | Challenge participants will inoculated intranasallly with reconstituted lyophilised Neisseria lactamica (lyoNlac). The initial dose will be 10^5 colony-forming units (CFU) and will be escalated or de-escalated by 1/2 - 1 log depending upon the proportion of volunteers colonies with viable N. lactamica. Receives: Biological: Lyophilised Neisseria lactamica |
What is being measured
The primary outcome is the main question the study is designed to answer.
Via the hospital Pathology service, analyse the haematology blood results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests haematology- haemoglobin - g/L,
Measured: 1 year
Via the hospital Pathology service, analyse the White Cell Count of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include haematology - White Cell Count - x10^9/L
Measured: 1 Year
Via the hospital Pathology service, analyse the Platelet Count of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include haematology - Platelet Count - x10^9/L
Measured: 1 Year
Via the hospital Pathology service, analyse the Biochemistry results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include Biochemistry - Sodium - mmol/L
Measured: 1 Year
Via the hospital Pathology service, analyse the CRP results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include Biochemistry - C-reactive protein - mg/L
Measured: 1 Year
Secondary outcomes (1)
The dose of lyophilised Neisseria lactamica required for nasopharyngeal colonisation in 80% of inoculees.
The dose will be confirmed by nasal swabs and nasal washes taken from participants and analysed for bacteria by CFU counts. The desired dose will be confirmed when 80% of participants are colonised.
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Oct 2019
- Study start1 Feb 2019
- Primary completion1 Feb 2020 (estimated)
- Study completion31 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Meningitis, BacterialStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- A prospective dose ranging human challenge study. Nasal inoculation with reconstituted, previously lyophilised Neisseria lactamica with dose escalation / de-escalation.
- Masking
- None (open label)
- Enrolment
- 35 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southampton
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital Southampton NHS Foundation Trust
- Responsible party
- Sponsor
- Investigators
- Robert C Read, Principal investigator, University of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04135053
- Sponsor's protocol ID
- Lac5-Nasal
- Acronym
- Lac5-Nasal
- Status last verified
- Oct 2019
- First submitted
- 27 Sep 2019
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gbesemete DF, Haidara F, Laver JR, Ibrahim M, MacLennan J, Dale AP, Gorringe AR, Traore Y, Diallo F, Badji H, Traore A, Onwuchekwa U, Jones E, Webb C, Guy J, Theodosiou AA, Faust SN, Sow SO, Heyderman RS, Tapia MD, Read RC. Controlled Human Infection of Healthy Adults With Lyophilized Neisseria lactamica Induces Asymptomatic, Immunogenic Nasopharyngeal Carriage in the United Kingdom and Mali. Open Forum Infect Dis. 2026 Jan 7;13(1):ofaf809. doi: 10.1093/ofid/ofaf809. eCollection 2026 Jan.
PubMed 41574175
Study at a glance
From the registry record, last updated by the sponsor on 22 Oct 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Human Controlled Infection Study to Assess Safety, Colonisation and Immunogenicity Following Nasal Inoculation With Reconstituted Lyophilised Wild Type Neisseria Lactamica
- ClinicalTrials.gov ID
- NCT04135053
- Acronym / sponsor ID
- Lac5-Nasal / Lac5-Nasal
- Conditions
- Meningitis, Bacterial
- Keywords
- meningitis, healthy volunteer
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 35 participants (estimated)
- Lead sponsor
- University of SouthamptonUniversity, hospital or other
- Collaborators
- University Hospital Southampton NHS Foundation Trust
- Study start
- 1 Feb 2019 (actual)
- Primary completion
- 1 Feb 2020 (estimated)
- Study completion
- 31 Dec 2021 (estimated)
- First posted
- 22 Oct 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is part of a series of projects to develop and test new vaccines for meningitis. Previously researchers have given nose drops containing N. lactamica to over 350 volunteers, and shown that many of them (35-60%) can become colonised with N. lactamica and become resistant to becoming colonised with N.meningitidis without causing any illness or disease. In the future the study team would like to find out how N.lactamica helps children resist N.meningitidis, and develop new vaccines that exploit that mechanism.
Detailed description
In this pilot research, the research team will develop and validate a modification of the methodology previously used in another UK-based human challenge experiments. The research to be conducted in this study will inform the study team whether intranasal inoculation of reconstituted lyophilised Nlac (hereafter, lyoNlac), can result in immunising colonisation of participants and the optimal dose to achieve this.
Previous challenges have been conducted using frozen stocks of Nlac but this is relatively unsatisfactory because of instability of frozen stocks, and will not be practical in Mali. The facility to reconstitute dry powdered lyoNlac into water and inoculate as a nose drop will greatly simplify the experimental method. However, it is not known whether lyoNlac can be inoculated directly into volunteers and induce successful colonisation.
In summary this is a pilot study of the safety, efficacy and immunogenicity of the intranasal inoculation of healthy human volunteers with lyoNlac. This study will determine the efficacy of lyoNlac as an agent for inducing nasopharyngeal colonisation with this organism, which is an important methodological development for ease of administration of Nlac in experimental human challenge studies. The study team will aim to determine the dose of inoculum required to induce colonisation in 80% of volunteers (the Standard Inoculum or SI). This SI will be used in future studies aiming to optimise duration of colonisation and immunogenicity induced by lyoNlac.
Study design
- Primary purpose
- Prevention
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- A prospective dose ranging human challenge study. Nasal inoculation with reconstituted, previously lyophilised Neisseria lactamica with dose escalation / de-escalation.
| Arm | Type | Receives |
|---|---|---|
| Challenge | Experimental | Biological: Lyophilised Neisseria lactamicaChallenge participants will inoculated intranasallly with reconstituted lyophilised Neisseria lactamica (lyoNlac). The initial dose will be 10^5 colony-forming units (CFU) and will be escalated or de-escalated by 1/2 - 1 log depending upon the proportion of volunteers colonies with viable N. lactamica. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- Healthy adults aged 18 to 45 years inclusive on the day of enrolment
- Fully conversant in the English language
- Able and willing (in the investigator's opinion) to comply with all study requirements
- Provide written informed consent to participate in the trial
- For females only, willingness to practice continuous effective contraception (see below) during the study and a negative pregnancy test on the day(s) of screening and inoculation
Key exclusion criteria (14 listed)
- Current active smokers defined as having smoked a cigarette or cigar in the last four weeks
- N. lactamica or N. meningitidis detected on throat swab or nasal wash taken at screening
- Individuals who have a current infection at the time of inoculation
- 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 been involved in clinical trials investigating meningococcal vaccines or experimental challenge with N. lactamica
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Lyophilised Neisseria lactamicaPreviously lyophilised Neisseria lactamica will be reconstituted and intranasally given to participants | Biological | Challenge |
Primary outcome
Via the hospital Pathology service, analyse the haematology blood results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Time frame: 1 year
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests haematology- haemoglobin - g/L,
Via the hospital Pathology service, analyse the White Cell Count of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Time frame: 1 Year
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include haematology - White Cell Count - x10^9/L
Via the hospital Pathology service, analyse the Platelet Count of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Time frame: 1 Year
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include haematology - Platelet Count - x10^9/L
Via the hospital Pathology service, analyse the Biochemistry results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Time frame: 1 Year
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include Biochemistry - Sodium - mmol/L
Via the hospital Pathology service, analyse the CRP results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points.
Time frame: 1 Year
Blood samples will be taken at standardised visits. Results will be compared to those results collected from baseline and pre-inoculation visits. Any change in results will be recorded and, if deemed required by the medical team, further tests requested. Standard tests include Biochemistry - C-reactive protein - mg/L
1 secondary outcome
The dose of lyophilised Neisseria lactamica required for nasopharyngeal colonisation in 80% of inoculees.
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Derived from this study: PubMed 41574175Gbesemete DF, Haidara F, Laver JR, Ibrahim M, MacLennan J, Dale AP, Gorringe AR, Traore Y, Diallo F, Badji H, Traore A, Onwuchekwa U, Jones E, Webb C, Guy J, Theodosiou AA, Faust SN, Sow SO, Heyderman RS, Tapia MD, Read RC. Controlled Human Infection of Healthy Adults With Lyophilized Neisseria lactamica Induces Asymptomatic, Immunogenic Nasopharyngeal Carriage in the United Kingdom and Mali. Open Forum Infect Dis. 2026 Jan 7;13(1):ofaf809. doi: 10.1093/ofid/ofaf809. eCollection 2026 Jan.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Robert C Read principal investigator
University of Southampton
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Lyophilised Neisseria lactamica in people with Meningitis, Bacterial, run by University of Southampton at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 22 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Diane Gbesemete (+44(0) 2381 204989, diane.gbesemete@uhs.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Via the hospital Pathology service, analyse the haematology blood results of healthy volunteers inoculated with reconstituted lyophilised wild type Neisseria lactamica, taken at specified time points. (time frame: 1 year). The study lists 5 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04135053, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Oct 2019.