Quorum SensingPhase 1NCT01201577
Biological Modulation of Bacterial QSSMs, Innate and Adaptive Immunity by Antibiotics, Probiotics and Prebiotics in Healthy Individuals
A Phase 1 study testing Bifidobacterium longum BB536, Active hexose correlated compound (AHCC) and Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC) in people with Quorum Sensing and Prebiotics, run by University of Nottingham at 1 site in United Kingdom.
Trial summary
It has recently been discovered that bacteria are able to communicate using specialised molecules known as Quorum Sensing Signalling Molecules (QSSMs). An accumulation of QSSMs in their surrounding environment allow for the bacteria to quantify the size of colonies. Read more about this study
- Who is it for?
- Ages 18 to 75 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Quorum Sensing, Prebiotics, Probiotics
- What is being tested?
- Bifidobacterium longum BB536, Active hexose correlated compound (AHCC) and Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC)
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Oct 2009to May 2011
- Phase
- 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 75 years
- Men only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Male volunteers
- Age 18-55 years
- Willing to participate and able to give informed consent
- Alcohol abstinence during study
Who cannot join
- Smokers/substance abusers
- Individuals with diabetes mellitus
- Oral/Intravenous steroids
- Allergy to azithromycin
- Individuals already taking regular medications/probiotics/nutritional supplements
- Individuals with chronic disease or currently under investigation
- Individuals with ≤3 bowel movements/week
- Individuals with ≥2 bowel movements/day
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
University of Nottingham
Nottingham, Nottinghamshire, NG7 2UH
About this study
It has recently been discovered that bacteria are able to communicate using specialised molecules known as Quorum Sensing Signalling Molecules (QSSMs). An accumulation of QSSMs in their surrounding environment allow for the bacteria to quantify the size of colonies. At specific colony sizes the concentration of QSSMs reaches a critical threshold leading to the activation of genes that cause an infection. It is by this mechanism that bacteria within a colony coordinate behaviour to activate infectivity when colony sizes are large enough to withstand defensive measures from the host's immune system. A disruption of quorum sensing may reduce the severity of infection and this has led to the development of inhibitors of quorum sensing as a new strategy in antibacterial therapy.
QSSMs are also thought to facilitate infection by other mechanisms and are able to influence the number and function of a specific type of immune cell known as an 'antigen presenting cell'. These cells are pivotal in allowing the immune system to recognise components of bacteria as foreign and thereby mount the appropriate response. It was found that large numbers of these types of cells underwent programmed cell death (cell suicide) in the presence of QSSMs compared to when QSSMs were absent. This mirrors the situation in blood sampled from patients with severe infections where there is a greater proportion of cell deaths among antigen presenting cells than other types of immune cell.
Read more
This study aims to establish in healthy volunteers, the mechanisms by which QSSMs affect immune cells and facilitate the spread of infection. Antibiotic administration in humans can alter the environment of the intestine and can lead to an overgrowth of harmful bacteria to potentially cause an infection. Probiotics supplements can prevent bacterial overgrowth and potentially reduce infective complications. The mechanism, which we aim to clarify, may involve changes in both the production of QSSMs and the function of immune cells.
Hypothesis
- Antibiotic use alters gut flora, leading to the appearance in the systemic circulation of bacterial QSSMs and changes in immune function of the host.
- Probiotics and/or prebiotics have beneficial effects by preserving the normal resident gut flora, thereby, modulating bacterial QSSMs and preserving the immune function of the host.
Aims
The aims of our study are 2 fold:
- Firstly, to study the effect of orally administered antibiotic on QSSMs (in faeces and blood) and on innate and adaptive immunity in healthy humans.
- Secondly, to study the effect of orally administered combinations of prebiotic, probiotic and antibiotic on QSSMs (in faeces and blood) and on innate and adaptive immunity in healthy humans.
- Conditions
- Quorum Sensing, Prebiotics, Probiotics, Sepsis
- Being tested
- Bifidobacterium longum BB536, Active hexose correlated compound (AHCC), Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC), Corn starch placebo capsule, Azithromycin
- Keywords
- Quorum sensing, Prebiotics, Probiotics, Sepsis
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bifidobacterium longum BB536Dietary supplement
2 capsules od
Active hexose correlated compound (AHCC)Dietary supplement
One capsule tds
Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC)Dietary supplement
One capsule tds (prebiotic) and two capsules od (probiotic)
Corn starch placebo capsuleDietary supplement
One capsule tds and two capsules od
AzithromycinDrug
250mg od
| Study group | Role | What they receive |
|---|---|---|
| Placebo/Probiotic | Active comparator | Not described Receives: Dietary Supplement: Bifidobacterium longum BB536; Drug: Azithromycin |
| Placebo/Prebiotic | Active comparator | Not described Receives: Dietary Supplement: Active hexose correlated compound (AHCC); Drug: Azithromycin |
| Prebiotic/Probiotic | Active comparator | Not described Receives: Dietary Supplement: Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC); Drug: Azithromycin |
| Placebo/Placebo | Placebo comparator | Not described Receives: Dietary Supplement: Corn starch placebo capsule; Drug: Azithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum QSSM level
Measured: 14 days
Secondary outcomes (1)
T cell Th1/Th2 ratio
Measured: 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Sep 2010 (estimated)
- Study startOct 2009
- Primary completionMay 2011
- Study completionMay 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Quorum SensingStudies of the same condition, open and under way.
- More trials run by University of NottinghamThe sponsor's other registered studies.
- 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 1
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Nottingham
- Sponsor type
- University, hospital or other
- Investigators
- Abeed Chowdhury, MB ChB BSc MRCS, Principal investigator, University of NottinghamDileep Lobo, MBBS DM FRCS, Study director, University of Nottingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01201577
- Sponsor's protocol ID
- 09GA014
- Status last verified
- May 2011
- First submitted
- 13 Sep 2010
- Last updated
- 1 Jun 2011
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Jun 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biological Modulation of Bacterial QSSMs, Innate and Adaptive Immunity by Antibiotics, Probiotics and Prebiotics in Healthy Individuals
- ClinicalTrials.gov ID
- NCT01201577
- Acronym / sponsor ID
- 09GA014
- Conditions
- Quorum Sensing, Prebiotics, Probiotics, Sepsis
- Keywords
- Quorum sensing, Prebiotics, Probiotics, Sepsis
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (estimated)
- Lead sponsor
- University of NottinghamUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- May 2011 (actual)
- Study completion
- May 2011 (actual)
- First posted
- 14 Sep 2010 (estimated)
- 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.
It has recently been discovered that bacteria are able to communicate using specialised molecules known as Quorum Sensing Signalling Molecules (QSSMs). An accumulation of QSSMs in their surrounding environment allow for the bacteria to quantify the size of colonies. At specific colony sizes the concentration of QSSMs reaches a critical threshold leading to the activation of genes that cause an infection. It is by this mechanism that bacteria within a colony coordinate behaviour to activate infectivity when colony sizes are large enough to withstand defensive measures from the host's immune system. A disruption of quorum sensing may reduce the severity of infection and this has led to the development of inhibitors of quorum sensing as a new strategy in antibacterial therapy.
QSSMs are also thought to facilitate infection by other mechanisms and are able to influence the number and function of a specific type of immune cell known as an 'antigen presenting cell'. These cells are pivotal in allowing the immune system to recognise components of bacteria as foreign and thereby mount the appropriate response. It was found that large numbers of these types of cells underwent programmed cell death (cell suicide) in the presence of QSSMs compared to when QSSMs were absent. This mirrors the situation in blood sampled from patients with severe infections where there is a greater proportion of cell deaths among antigen presenting cells than other types of immune cell.
This study aims to establish in healthy volunteers, the mechanisms by which QSSMs affect immune cells and facilitate the spread of infection. Antibiotic administration in humans can alter the environment of the intestine and can lead to an overgrowth of harmful bacteria to potentially cause an infection. Probiotics supplements can prevent bacterial overgrowth and potentially reduce infective complications. The mechanism, which we aim to clarify, may involve changes in both the production of QSSMs and the function of immune cells.
Hypothesis
- Antibiotic use alters gut flora, leading to the appearance in the systemic circulation of bacterial QSSMs and changes in immune function of the host.
- Probiotics and/or prebiotics have beneficial effects by preserving the normal resident gut flora, thereby, modulating bacterial QSSMs and preserving the immune function of the host.
Aims
The aims of our study are 2 fold:
- Firstly, to study the effect of orally administered antibiotic on QSSMs (in faeces and blood) and on innate and adaptive immunity in healthy humans.
- Secondly, to study the effect of orally administered combinations of prebiotic, probiotic and antibiotic on QSSMs (in faeces and blood) and on innate and adaptive immunity in healthy humans.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Factorial
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo/Probiotic | Active comparator | Dietary Supplement: Bifidobacterium longum BB536, Drug: Azithromycin |
| Placebo/Prebiotic | Active comparator | Dietary Supplement: Active hexose correlated compound (AHCC), Drug: Azithromycin |
| Prebiotic/Probiotic | Active comparator | Dietary Supplement: Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC), Drug: Azithromycin |
| Placebo/Placebo | Placebo comparator | Dietary Supplement: Corn starch placebo capsule, Drug: Azithromycin |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Male volunteers
- Age 18-55 years
- Willing to participate and able to give informed consent
- Alcohol abstinence during study
Key exclusion criteria (8 listed)
- Smokers/substance abusers
- Individuals with diabetes mellitus
- Oral/Intravenous steroids
- Allergy to azithromycin
- Individuals already taking regular medications/probiotics/nutritional supplements
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 |
|---|---|---|
| Bifidobacterium longum BB5362 capsules od | Dietary supplement | Placebo/Probiotic |
| Active hexose correlated compound (AHCC)One capsule tds | Dietary supplement | Placebo/Prebiotic |
| Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC)One capsule tds (prebiotic) and two capsules od (probiotic) | Dietary supplement | Prebiotic/Probiotic |
| Corn starch placebo capsuleOne capsule tds and two capsules od | Dietary supplement | Placebo/Placebo |
| Azithromycin250mg od | Drug | Placebo/Placebo, Placebo/Prebiotic, Placebo/Probiotic, Prebiotic/Probiotic |
Primary outcome
Serum QSSM level
Time frame: 14 days
1 secondary outcome
T cell Th1/Th2 ratio
Time frame: 14 days
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 1 Jun 2011.
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.
Abeed Chowdhury, MB ChB BSc MRCS principal investigator
University of Nottingham
Dileep Lobo, MBBS DM FRCS study director
University of Nottingham
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Bifidobacterium longum BB536, Active hexose correlated compound (AHCC) and Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC) in people with Quorum Sensing and Prebiotics, run by University of Nottingham 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 4 inclusion and 8 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 1 Jun 2011. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Serum QSSM level (time frame: 14 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Jun 2011.