Ignite Creation Date:
2024-05-05 @ 10:16 PM
Last Modification Date:
2024-10-26 @ 10:16 AM
Study NCT ID:
NCT01074775
Status:
COMPLETED
Last Update Posted:
2010-02-24
First Post:
2010-02-23
Brief Title:
Human Innate Immune Responses To Mycobacterial Aerodigestive Tract Infection
Sponsor:
St Georges University of London
Organization:
St Georges University of London
Study Overview
Official Title:
An Investigation Of In Vivo Human Innate Immune Responses To Mycobacterial Aerodigestive Tract Infection
Status:
COMPLETED
Status Verified Date:
2010-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
UBC-INNATE01
Brief Summary:
The approach we will use is to employ measurement of the activation of white blood cells to look at patterns of responses during a controlled infection of the gut with Mycobacterium bovis M bovis can be conveniently obtained in a safe and pure form as an oral vaccine By giving three challenges of M bovis to the gut we will simulate repeated gut infections with this organism We can then compare the activation of cells in the blood to the immune responses seen after each challenge to determine whether the non-specific defences of the gut can block each subsequent infection
Detailed Description:
The approach we will use is to employ immune readouts and genomics to look at patterns of responses during a controlled infectious challenge of the human gut
Genomics uses Affymetrix gene arrays and other techniques to determine the profile of gene expression When a gene is switched on it makes mRNA that the body uses as a template to make proteins We will extract all the mRNA from white blood cells before during and after an infection The gene chips have hundreds or thousands of mini-sensors that can measure how much mRNA from any particular gene is present in the sample Thus we can begin to see which genes are switch on or off or unaffected inside white blood cells during the stages of a developing innate immune response This allows us to monitor the bodys response to an infection and to see which families of genes are important at the different stages of gut infection
The BCG vaccine is derived from Mycobacterium bovis the full name of the organism is Mycobacterium bovis Baccille Calmette Guérin In this study we propose to use an oral BCG preparation produced as a prophylactic and therapeutic oral vaccine as a safe model for natural gut infection with pathogenic Mycobacterium bovis The cell wall of mycobacteria such as BCG is a powerful immune adjuvant an adjuvant is a substance that enhances an immune response as the lipids sugars and proteins in the cell wall interact strongly with the molecules of the innate immune system It therefore provides a safe but highly effective way to stimulate innate immunity under natural conditions of gut infection This first model has been selected as it reflects a real world high priority area of disease prevention while having a high level of safety and reproducibility in the oral BCG model
By carefully delivering oral BCG challenges to healthy volunteers under controlled conditions we can reduce the noise and background activity in the proteomic and genomic assays we will use to profile the developing innate immune response We can check that the BCG has indeed colonised and infected the subject by measuring the specific adaptive T cell and antibody responses using sensitive assays we have developed in previous studies to detect these immune responses This is a critical aspect of the study if we detect the BCG-specific T cell responses we can be assured that the infection has taken place and so can interpret the profiles we see in the immunology and genomics
If we see an immune response we can relate any innate immune activation to colonisation with BCG In contrast even if we see no immune responses but can be sure that the vaccine was delivered properly in a viable formulation which we will do by adhering to strict Good Clinical Practice then we can look at features in the genomic and proteomic profiles in the baseline measurements before infection that may predict the failure of the organisms to infect
By collecting data of other events such as intercurrent illnesses or other adverse events we can also determine whether changes in the proteomic or gene expression profiles are indeed due to the model infection or extraneous events This preliminary study will enable us to refine expensive techniques protocols and assays to let us focus in more detail in subsequent studies
This study will be conducted according to the Standard Operating Procedures SOPs of the St Georges Vaccine Institute Up to 10 subjects will be included in this study The study will consist of a pre-study screening visit and 23 visits over a period of 12 month at the times indicated in the schedule for investigation
Genomics uses Affymetrix gene arrays and other techniques to determine the profile of gene expression When a gene is switched on it makes mRNA that the body uses as a template to make proteins We will extract all the mRNA from white blood cells before during and after an infection The gene chips have hundreds or thousands of mini-sensors that can measure how much mRNA from any particular gene is present in the sample Thus we can begin to see which genes are switch on or off or unaffected inside white blood cells during the stages of a developing innate immune response This allows us to monitor the bodys response to an infection and to see which families of genes are important at the different stages of gut infection
The BCG vaccine is derived from Mycobacterium bovis the full name of the organism is Mycobacterium bovis Baccille Calmette Guérin In this study we propose to use an oral BCG preparation produced as a prophylactic and therapeutic oral vaccine as a safe model for natural gut infection with pathogenic Mycobacterium bovis The cell wall of mycobacteria such as BCG is a powerful immune adjuvant an adjuvant is a substance that enhances an immune response as the lipids sugars and proteins in the cell wall interact strongly with the molecules of the innate immune system It therefore provides a safe but highly effective way to stimulate innate immunity under natural conditions of gut infection This first model has been selected as it reflects a real world high priority area of disease prevention while having a high level of safety and reproducibility in the oral BCG model
By carefully delivering oral BCG challenges to healthy volunteers under controlled conditions we can reduce the noise and background activity in the proteomic and genomic assays we will use to profile the developing innate immune response We can check that the BCG has indeed colonised and infected the subject by measuring the specific adaptive T cell and antibody responses using sensitive assays we have developed in previous studies to detect these immune responses This is a critical aspect of the study if we detect the BCG-specific T cell responses we can be assured that the infection has taken place and so can interpret the profiles we see in the immunology and genomics
If we see an immune response we can relate any innate immune activation to colonisation with BCG In contrast even if we see no immune responses but can be sure that the vaccine was delivered properly in a viable formulation which we will do by adhering to strict Good Clinical Practice then we can look at features in the genomic and proteomic profiles in the baseline measurements before infection that may predict the failure of the organisms to infect
By collecting data of other events such as intercurrent illnesses or other adverse events we can also determine whether changes in the proteomic or gene expression profiles are indeed due to the model infection or extraneous events This preliminary study will enable us to refine expensive techniques protocols and assays to let us focus in more detail in subsequent studies
This study will be conducted according to the Standard Operating Procedures SOPs of the St Georges Vaccine Institute Up to 10 subjects will be included in this study The study will consist of a pre-study screening visit and 23 visits over a period of 12 month at the times indicated in the schedule for investigation
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None