CASE.EDU:    HOME | DIRECTORIES | SEARCH
Case Western Reserve University Tuberculosis Research Unit
  Integrating research to combat the global TB epidemic
 
 

 

TBRU Studies

Oversight by Scientific Working Groups (SWG)

TBRU Statement of Work -
Research Questions Addressed
by TBRU Multi-Disciplinary Research Studies

Kawempe Community Health Study

Innate Immunity Study & Infant Predictor Study

BCG Study

Nucleic Acid Amplification & Pilot Immunology Study

Immunology SWG

Genetics SWG

Surrogate Markers of Response to TB Therapy SWG

MTB Strains Working Group

GENERAL SCOPE

1a) Design, conduct, and direct clinical studies in human TB to establish markers to identify individuals at highest risk for progression to TB disease after infection with MTB

 

 

I

G

 

M

1b) Design, conduct, and direct clinical studies in human TB to establish markers to characterize correlates of response to therapy and vaccination that can establish useful early estimates of clinical efficacy of new health care interventions

 

I

G

S

M

1c) Design, conduct, and direct clinical studies in human TB to establish markers to eventually contribute to the identification of new diagnostic tests and improved therapeutic and vaccination strategies

I

 

S

M

CLINICAL STUDY PLAN – DESIGN & CONDUCT STUDIES IN THE FOLLOWING AREAS:

2a) Characterization of the human immune response to BCG in target populations, such as children, to better define expectation and clinical endpoints for new TB vaccines in general

 

 

I

G

 

 

2b) Characterization of immune responses in persons who successfully control infection with MTB versus those who progress to active disease to facilitate selection of at-risk persons for clinical studies and the development of diagnostics

 

 

I

G

 

M

2c) Characterization of human immune responses or other biological markers in response to drug therapy to define early markers of efficacy and possible approaches for combining drug therapy with vaccination strategies

 

 

I

 

S

 

2d) Kinetics of human immune responses after vaccination and infection to facilitate selection of boosting strategies for vaccine studies

 

I

 

 

 

ADDITIONAL RESEARCH QUESTIONS TO BE ADDRESSED:

1)  Why do most HIV negative persons successfully control MTB infection while some progress to active TB disease?

 

I

G

 

 

1a) Study design shall allow longitudinal assessment, in one or more TB endemic countries, of immunological biochemical, microbiological, host genetic or other biochemical markers that identify various stages of infection and disease in HIV negative adult and pediatric populations

 

 

 

I

G

 

M

1b) Study outcomes shall provide epidemiological data for the characterization of disease prevalence and incidence, and transmission dynamics of MTB strains

 

 

 

 

 

M

1c) Studies may include evaluation of one or more promising diagnostic tests made available through collaborations with the research community to maximize information obtained from clinical studies

 

I

 

S

 

1d) Studies shall maximize utilizaton of local expertise to conduct assays and anlyses with human derived specimens. 

I

G

S

M

1e) Study endpoints shall be of sufficient practical nature to have the potential to aid in the development of diagnostic test(s) to identify persons at highest risk for progressing from MTB infection to active TB disease

 

 

 

S

 

2) Why does BCG protect some individuals and not others from TB disease and what are the kinetics of the immune response after vaccination with BCG versus after infection with MTB?

 

I

G

 

 

2a) Studies shall be conducted in one or more TB endemic countries that routinely use BCG vaccination as part of their control strategies

 

I

G

 

 

2b) Study design shall include pediatric populations and may include HIV+ or HIV- TB co-infected individuals

 

 

I

G

 

 

2c) Study design shall include identification and characterization of the kinetics of the immune response after vaccination versus after infection with MTB

 

I

 

 

 

2d) Study results should provide data that have the potential to inform local TB care practices.

I

 

 

 

2e) Study endpoints shall be of sufficient practical nature to have the potential to aid in the development of clinical endpoints for the evaluation of novel vaccine candidates and to inform expectations for benchmarks in clinical vaccine development for TB

I

 

 

 

2f) Study endpoints shall be of sufficient practical nature to have the potential to aid in the development of diagnostic tests to identify immune competent persons infected with MTB and not be compromised by standard BCG vaccination or presence of other mycobacteria

 

 

G

 

 

2g) Study design shall not include extended observational studies of TB incidence as a result of BCG vaccination

I

 

 

 

3) What immune responses or other biological markers that predict relevant clinical outcomes can be measured in response to drug therapy or vaccines?

 

 

I

G

S

 

3a) Clinical studies shall be conducted in one or more TB endemic countries

I

G

S

 

3b) Study design may include HIV co-infected individuals

 

I

G

S

 

3c) Studies may be conducted with existing or novel drugs or vaccines, available through the research community, as part of early stage human clinical studies or as part of Phase I or Phase II clinical trials

 

 

S

 

3d) Study design shall include a comprehensive panel of immunological and other biological evaluations to maximize information content derived from these studies.  These laboratory studies may be conducted in TB non-endemic countries, if appropriate

I

G

 

 

3e) Study results are expected to contribute to the identification of early surrogate markers of efficacy.  It is expected that more than one marker will have to be utilized to estimate clinical efficacy of vaccines and/or drug therapies.

 

 

S

M