Meningitis, BacterialEarly Phase 1Lac-7NCT03633474
Defining the Immune Response to Nasopharyngeal Colonisation by the Commensal Neisseria Lactamica
A Early Phase 1 study testing N. lactamica and PBS only in people with Meningitis, Bacterial, run by University of Southampton at 1 site in United Kingdom.
Trial summary
Neisseria meningitidis is a 'bad bacteria' which lives harmlessly in the nose and throat of many young adults (a process called colonisation). However, it can occasionally cause serious disease including meningitis. 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?
- N. lactamica and PBS only
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 31 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Sep 2018to 1 Sep 2019
- Phase
- Early Phase 1
- 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.
- Written informed consent to participate in the study.
- For females only, willingness to practice continuous effective contraception (see below) during the study and negative pregnancy test at visit 1 (screening).
Who cannot join
- Active smokers.
- N. meningitidis or N. lactamica detected following culture of throat swab or nasal wash taken before the challenge.
- Individuals who have a current infection at the time of inoculation.
- Individuals who have been involved in other clinical studies/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 studies/trials investigating meningococcal vaccines or experimental challenge with N. lactamica.
- Use of oral or intravenous antibiotics within the period 30 days prior to the challenge.
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- Any confirmed or suspected immunosuppressive or immunocompromised state, including HIV infection, asplenia, history of recurrent severe infections or use (more than 14 days) of immunosuppressant medication within the past 6 months (topical/inhaled steroids are allowed).
- Use of immunoglobulins or blood products within 3 months prior to enrolment.
- History of blood donation within the past 12 weeks for male volunteers, or 16 weeks for female volunteers.
- Allergy to yeast extract.
- 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
NIHR Southampton Clinical Research Facility
Southampton
About this study
Official title: Lactamica 7: Defining the Immune Response to Nasopharyngeal Colonisation by the Commensal Neisseria Lactamica
Neisseria meningitidis is a 'bad bacteria' which lives harmlessly in the nose and throat of many young adults (a process called colonisation). However, it can occasionally cause serious disease including meningitis. Vaccines have proven effective in preventing disease associated with a number of strains of this bacterium, however some disease-causing strains are not covered by currently available vaccines. This research is focused on exploring new approaches to preventing colonisation and disease caused by this bacterium.
Neisseria lactamica is a 'good bacteria' that colonises the nose and throat of young children. It does not cause disease in healthy people. In a previous study it has been demonstrated that the introduction of Neisseria lactamica into the noses of healthy adult volunteers resulted in a significant decrease in Neisseria meningitidis colonisation. However, it is not yet understood why this effect occurs. One theory is that the immune response the body mounts in response to colonisation with the 'good bacteria' cross-reacts with the 'bad bacteria' and in so doing eradicates the bad bacteria from the nose and throat. This study aims to outline the nature of the immune responses mounted in response to colonisation with the good bacteria, N. lactamica, after introducing it into the noses of healthy adult volunteers. In addition, the study aims to establish how the introduction of the good bacteria changes the other bacterial populations that live in the nose and throat.
Read the detailed description
The clinical trial is a controlled, volunteer blinded, N. lactamica human challenge study to enable N. lactamica-specific cellular immune responses to be outlined in detail. In addition, The aim is to determine whether responses directed towards N. lactamica are cross-reactive with N. meningitidis.
Following enrolment onto the study, non-meningococcal carriers (as determined by microbiological culture of nasopharyngeal wash and retropharyngeal swab) will be challenged intra-nasally with either 10-5 cfu of N. lactamica wild-type strain Y92-1009 (30,31) suspended in sterile phosphate buffered saline (PBS), as used in previous studies, or PBS alone (control group).
Following inoculation on Day 0, biological samples (nasal wash, nasal secretion, throat swabs and blood) will be taken from all volunteers on days +7 (+/-3), +14(+/-3) and +28(+/-5) post-challenge. On the day of inoculation (Day 0) the biological samples listed will be taken except for the nasal wash.
- lactamica-specific B-cell and CD4+ memory T-cell responses will be measured in blood using a selection of in vitro assays and the results compared longitudinally in N. lactamica challenged (colonised or non-colonised) vs. control challenged subjects. The experiments will establish the nature of T-cell and B-cell memory responses and plasma B-cell responses induced in response to N. lactamica colonisation and will determine if these responses are cross-reactive with N. meningitidis. Mucosal immune profiling and microbiome analyses will be performed on nasal secretion and nasal bacterial samples, respectively. Any remaining biological samples (following experiments performed to meet the current study objectives) will be transferred to our registered human tissue bank to enable future studies following additional ethics approval by the relevant bodies.
- Conditions
- Meningitis, Bacterial
- Being tested
- N. lactamica, PBS only
- Keywords
- Healthy volunteer, Human Challenge study
- Medical subject headings
- Meningitis, Bacterial
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N. lactamicaBiological
Stocks of N. lactamica (strain Y92-1009, sequence type 3493, clonal complex 613) in Frantz medium containing 30% (v/v) glycerol have been previously prepared using the Good Manufacturing Practices pharmaceutical manufacturing facilities at Public Health England (Porton Down, United Kingdom).
PBS onlyOther
Sterile PBS only containing no bacteria
| Study group | Role | What they receive |
|---|---|---|
| N. Lactamica in PBS | Experimental | Wild-type Neisseria lactamica (strain Y92-1009, sequence type 3493, clonal complex 613) will be used for this human challenge experiment. This strain is identical to that utilised in our previous challenge experiments (>350 volunteers to date). Receives: Biological: N. lactamica |
| PBS Control | Placebo comparator | PBS only control. Volunteers randomized to this arm will receive a PBS only solution which contains no bacteria. Receives: Other: PBS only |
What is being measured
The primary outcome is the main question the study is designed to answer.
To measure host T-cell and B-cell memory responses and plasma B-cell responses in blood to experimentally-induced nasopharyngeal colonisation with N. lactamica.
Measurements from baseline will compare the host T and B-cell memory response (ug/mL) to samples taken post inoculation.
Measured: Up to Day 33
Secondary outcomes (1)
Determine if N. lactamica-specific CD4+ T-cell memory responses detected in blood cross-react with N. meningitidis.
From PBMC isolation of participants blood, measure if the T-cell response reacts when presented with N. meningitidis (ug/mL)
Measured: Up to Day 33
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2018
- Study start1 Sep 2018
- Primary completion1 Sep 2019
- Study completion1 Sep 2019
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
- Early Phase 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Volunteers will be blinded to the inoculum type received (i.e. N. lactamica or PBS control) throughout the study duration. Nasal secretion and throat swabs will be taken to enable mucosal immune profiling and microbiome analyses to be performed. Subjects will be screened for nasopharyngeal N. meningitidis carriage -28 to -7 days (visit 1) and non-Neisseria spp. carriers will be challenged with either 105 cfu N. lactamica suspended in PBS or PBS only control (day 0, visit 2). Volunteers identified as carriers of N. meningitidis at visit 1 will be excluded from the study and will not progress to experimental human challenge. Biological samples (nasal secretion, microbiome swab and blood) will be collected from volunteers who progress to the challenge (visit 2, Day 0) and on days +7 (+/-3), +14 (+/-3) and +28 (+/-5) post-challenge. Nasal wash sampling will not be taken at the challenge visit (Day 0) but will be taken on days +7(+/-3), +14 (+/-3) and +28 (+/-5) post-challenge.
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 31 participants (actual)
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
- Adam P Dale, Principal investigator, University of Southampton
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03633474
- Sponsor's protocol ID
- Lactamica-7
- Acronym
- Lac-7
- Status last verified
- Oct 2019
- First submitted
- 13 Aug 2018
- Last updated
- 22 Oct 2019
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Dale AP, Theodosiou AA, Gbesemete DF, Guy JM, Jones EF, Hill AR, Ibrahim MM, de Graaf H, Ahmed M, Faust SN, Gorringe AR, Polak ME, Laver JR, Read RC. Effect of colonisation with Neisseria lactamica on cross-reactive anti-meningococcal B-cell responses: a randomised, controlled, human infection trial. Lancet Microbe. 2022 Dec;3(12):e931-e943. doi: 10.1016/S2666-5247(22)00283-X.
PubMed 36462524
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
- Lactamica 7: Defining the Immune Response to Nasopharyngeal Colonisation by the Commensal Neisseria Lactamica
- ClinicalTrials.gov ID
- NCT03633474
- Acronym / sponsor ID
- Lac-7 / Lactamica-7
- Conditions
- Meningitis, Bacterial
- Keywords
- Healthy volunteer, Human Challenge study
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 31 participants (actual)
- Lead sponsor
- University of SouthamptonUniversity, hospital or other
- Collaborators
- University Hospital Southampton NHS Foundation Trust
- Study start
- 1 Sep 2018 (actual)
- Primary completion
- 1 Sep 2019 (actual)
- Study completion
- 1 Sep 2019 (actual)
- First posted
- 16 Aug 2018 (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.
Neisseria meningitidis is a 'bad bacteria' which lives harmlessly in the nose and throat of many young adults (a process called colonisation). However, it can occasionally cause serious disease including meningitis. Vaccines have proven effective in preventing disease associated with a number of strains of this bacterium, however some disease-causing strains are not covered by currently available vaccines. This research is focused on exploring new approaches to preventing colonisation and disease caused by this bacterium.
Neisseria lactamica is a 'good bacteria' that colonises the nose and throat of young children. It does not cause disease in healthy people. In a previous study it has been demonstrated that the introduction of Neisseria lactamica into the noses of healthy adult volunteers resulted in a significant decrease in Neisseria meningitidis colonisation. However, it is not yet understood why this effect occurs. One theory is that the immune response the body mounts in response to colonisation with the 'good bacteria' cross-reacts with the 'bad bacteria' and in so doing eradicates the bad bacteria from the nose and throat. This study aims to outline the nature of the immune responses mounted in response to colonisation with the good bacteria, N. lactamica, after introducing it into the noses of healthy adult volunteers. In addition, the study aims to establish how the introduction of the good bacteria changes the other bacterial populations that live in the nose and throat.
Detailed description
The clinical trial is a controlled, volunteer blinded, N. lactamica human challenge study to enable N. lactamica-specific cellular immune responses to be outlined in detail. In addition, The aim is to determine whether responses directed towards N. lactamica are cross-reactive with N. meningitidis.
Following enrolment onto the study, non-meningococcal carriers (as determined by microbiological culture of nasopharyngeal wash and retropharyngeal swab) will be challenged intra-nasally with either 10-5 cfu of N. lactamica wild-type strain Y92-1009 (30,31) suspended in sterile phosphate buffered saline (PBS), as used in previous studies, or PBS alone (control group).
Following inoculation on Day 0, biological samples (nasal wash, nasal secretion, throat swabs and blood) will be taken from all volunteers on days +7 (+/-3), +14(+/-3) and +28(+/-5) post-challenge. On the day of inoculation (Day 0) the biological samples listed will be taken except for the nasal wash.
- lactamica-specific B-cell and CD4+ memory T-cell responses will be measured in blood using a selection of in vitro assays and the results compared longitudinally in N. lactamica challenged (colonised or non-colonised) vs. control challenged subjects. The experiments will establish the nature of T-cell and B-cell memory responses and plasma B-cell responses induced in response to N. lactamica colonisation and will determine if these responses are cross-reactive with N. meningitidis. Mucosal immune profiling and microbiome analyses will be performed on nasal secretion and nasal bacterial samples, respectively. Any remaining biological samples (following experiments performed to meet the current study objectives) will be transferred to our registered human tissue bank to enable future studies following additional ethics approval by the relevant bodies.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
- Model description
- Volunteers will be blinded to the inoculum type received (i.e. N. lactamica or PBS control) throughout the study duration. Nasal secretion and throat swabs will be taken to enable mucosal immune profiling and microbiome analyses to be performed. Subjects will be screened for nasopharyngeal N. meningitidis carriage -28 to -7 days (visit 1) and non-Neisseria spp. carriers will be challenged with either 105 cfu N. lactamica suspended in PBS or PBS only control (day 0, visit 2). Volunteers identified as carriers of N. meningitidis at visit 1 will be excluded from the study and will not progress to experimental human challenge. Biological samples (nasal secretion, microbiome swab and blood) will be collected from volunteers who progress to the challenge (visit 2, Day 0) and on days +7 (+/-3), +14 (+/-3) and +28 (+/-5) post-challenge. Nasal wash sampling will not be taken at the challenge visit (Day 0) but will be taken on days +7(+/-3), +14 (+/-3) and +28 (+/-5) post-challenge.
| Arm | Type | Receives |
|---|---|---|
| N. Lactamica in PBS | Experimental | Biological: N. lactamicaWild-type Neisseria lactamica (strain Y92-1009, sequence type 3493, clonal complex 613) will be used for this human challenge experiment. This strain is identical to that utilised in our previous challenge experiments (>350 volunteers to date). |
| PBS Control | Placebo comparator | Other: PBS onlyPBS only control. Volunteers randomized to this arm will receive a PBS only solution which contains no bacteria. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (5 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.
- Written informed consent to participate in the study.
- For females only, willingness to practice continuous effective contraception (see below) during the study and negative pregnancy test at visit 1 (screening).
Key exclusion criteria (13 listed)
- Active smokers.
- N. meningitidis or N. lactamica detected following culture of throat swab or nasal wash taken before the challenge.
- Individuals who have a current infection at the time of inoculation.
- Individuals who have been involved in other clinical studies/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 studies/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 |
|---|---|---|
| N. lactamicaStocks of N. lactamica (strain Y92-1009, sequence type 3493, clonal complex 613) in Frantz medium containing 30% (v/v) glycerol have been previously prepared using the Good Manufacturing Practices pharmaceutical manufacturing facilities at Public Health England (Porton Down, United Kingdom). | Biological | N. Lactamica in PBS |
| PBS onlySterile PBS only containing no bacteria | Other | PBS Control |
Primary outcome
To measure host T-cell and B-cell memory responses and plasma B-cell responses in blood to experimentally-induced nasopharyngeal colonisation with N. lactamica.
Time frame: Up to Day 33
Measurements from baseline will compare the host T and B-cell memory response (ug/mL) to samples taken post inoculation.
1 secondary outcome
Determine if N. lactamica-specific CD4+ T-cell memory responses detected in blood cross-react with N. meningitidis.
Time frame: Up to Day 33
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Oct 2019.
- Derived from this study: PubMed 36462524Dale AP, Theodosiou AA, Gbesemete DF, Guy JM, Jones EF, Hill AR, Ibrahim MM, de Graaf H, Ahmed M, Faust SN, Gorringe AR, Polak ME, Laver JR, Read RC. Effect of colonisation with Neisseria lactamica on cross-reactive anti-meningococcal B-cell responses: a randomised, controlled, human infection trial. Lancet Microbe. 2022 Dec;3(12):e931-e943. doi: 10.1016/S2666-5247(22)00283-X.
- Individual participant dataSharing planned: Undecided
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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.
Adam P Dale 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 Early Phase 1 study testing N. lactamica and PBS only 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 5 inclusion and 13 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: finished, 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To measure host T-cell and B-cell memory responses and plasma B-cell responses in blood to experimentally-induced nasopharyngeal colonisation with N. lactamica. (time frame: Up to Day 33). 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 NCT03633474, 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.