Biological Modulation of Bacterial QSSMs, Innate and Adaptive Immunity by Antibiotics, Probiotics and Prebiotics in Healthy Individuals

NCT01201577 | Completed Phase 1

• 1 other identifier: 09GA014
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief 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. 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

1. 1.Antibiotic use alters gut flora, leading to the appearance in the systemic circulation of bacterial QSSMs and changes in immune function of the host.
2. 2.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.
3. 3.Firstly, to study the effect of orally administered antibiotic on QSSMs (in faeces and blood) and on innate and adaptive immunity in healthy humans.
4. 4.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

Keywords

Quorum sensing; Prebiotics; Probiotics; Sepsis

Outcome Measures

Primary Outcomes (1)

• Serum QSSM level

  14 days

Secondary Outcomes (1)

• T cell Th1/Th2 ratio

  14 days

Study Arms (4)

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

Interventions

Bifidobacterium longum BB536 DIETARY_SUPPLEMENT

2 capsules od

Placebo/Probiotic

Active hexose correlated compound (AHCC) DIETARY_SUPPLEMENT

One capsule tds

Placebo/Prebiotic

Bifidobacterium longum BB536 and Active hexose correlated compound (AHCC) DIETARY_SUPPLEMENT

One capsule tds (prebiotic) and two capsules od (probiotic)

Prebiotic/Probiotic

Corn starch placebo capsule DIETARY_SUPPLEMENT

One capsule tds and two capsules od

Placebo/Placebo

Azithromycin DRUG

250mg od

Placebo/Placebo; Placebo/Prebiotic; Placebo/Probiotic; Prebiotic/Probiotic

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male volunteers
• Age 18-55 years
• Willing to participate and able to give informed consent
• Alcohol abstinence during study

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

University of Nottingham

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

MeSH Terms

Conditions

Sepsis

Interventions

Active Hexose Correlated Compound; Azithromycin

Condition Hierarchy (Ancestors)

Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Abeed Chowdhury, MB ChB BSc MRCS

  University of Nottingham

  PRINCIPAL INVESTIGATOR

• Dileep Lobo, MBBS DM FRCS

  University of Nottingham

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: September 13, 2010
• First Posted: September 14, 2010
• Study Start: October 1, 2009
• Primary Completion: May 1, 2011
• Study Completion: May 1, 2011
• Last Updated: June 1, 2011

Record last verified: 2011-05

Locations

GB (1)