Comorbidities and Coinfections in Latent TB (COMBINE-TB)
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|ClinicalTrials.gov Identifier: NCT04642755|
Recruitment Status : Not yet recruiting
First Posted : November 24, 2020
Last Update Posted : November 24, 2020
Approximately 2 billion people worldwide are infected with Mycobacterium tuberculosis (TB), with 90% of individuals having latent infection (LTBI). The control of TB requires clearly delineated helper T cell (Th) 1 responses and, to a lesser extent, Th17 responses, which both play important roles in the induction and maintenance of protective immune responses in mouse models of TB infection and in the prevention of active disease, as seen in LTBI. During latency, M. tuberculosis is contained in localized granulomas. Mycobacteria specific T cells mediate delayed type hypersensitivity reactions to purified protein derivative (PPD), and this reaction is generally considered to indicate an LTBI status in the absence of demonstrable active infection.
Among the various risk factors that are known to play a role in promoting active TB, HIV is the most well studied and described. However, in low-HIV-endemic countries like India, other risk factors might play a more prominent role in active TB pathogenesis. These include malnutrition, diabetes mellitus (DM), and helminth infections. LTBI individuals with these comorbidities or coinfections could be at a higher risk for developing active TB than their "healthy" LTBI counterparts without these comorbidities. Thus, it is imperative to study the pathogenesis of TB infection and disease in these "at risk" populations.
In this study, we will estimate the prevalence of severe to moderate malnutrition, uncontrolled DM, and helminth infections in LTBI-positive individuals. We will collect samples from a cohort of individuals with LTBI, those with LTBI and coexistent malnutrition, DM, or helminth coinfection, and those without any of these conditions. Individual participation may last up to 6 months. The main objective of the study is to estimate the prevalence of malnutrition, DM, and helminth infections in LTBI individuals.
Simultaneously, we will perform transcriptomic, proteomic, and metabolomic assays, including profiles in serum and urine, to determine the biosignature portfolio of these individuals. In addition, immunological assays examining cytokine/chemokine signatures as well as other immune parameters related to innate and adaptive responses will be performed to enhance the understanding of the immunological cross talk between LTBI and malnutrition, DM, and helminth infections.
|Condition or disease|
|Latent Tuberculosis Diabete Mellitus Malnutrition Helminth Infection|
|Study Type :||Observational [Patient Registry]|
|Estimated Enrollment :||300 participants|
|Target Follow-Up Duration:||6 Months|
|Official Title:||A Cross-sectional Study to Estimate the Influence of Malnutrition, Diabetes Mellitus and Helminth Infections on Biosignatures in Latent Tuberculosis in a South Indian Population|
|Estimated Study Start Date :||January 2021|
|Estimated Primary Completion Date :||December 2025|
|Estimated Study Completion Date :||December 2025|
LTBI+ and severe to moderate malnutrition
LTBI+ and uncontrolled DM
LTBI+ and helminth infection
LTBI+ with more than one of the above conditions (severe to moderate malnutrition, DM, helminth infection)
"Healthy" LTBI+ controls who are negative for all of the above conditions (severe to moderate malnutrition, DM, helminth infection)
Healthy LTBI negative controls with none of the above conditions (severe to moderate malnutrition, DM, helminth infection).
- Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures [ Time Frame: 6 months ]Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures
Biospecimen Retention: Samples With DNA
Tempus or PAXgene tube blood collection for DNA and RNA isolation for experimental studies and storage for future research. No human genetic testing will be performed under this protocol.
Stool samples will be collected in specialized containers and will be used for DNA extraction and storage. At screening, stool DNA for qPCR diagnostics to detect hookworms, Ascaris, Strongyloides, and Trichuris.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04642755
|Contact: Subash Babu, MBBS, PhDemail@example.com|
|Contact: Pradeep Menon, MBBS,DPM,MPHfirstname.lastname@example.org|
|Principal Investigator:||Subash Babu, MBBS, PhD||National Institute for Research in Tuberculosis|
|Principal Investigator:||Thomas B Nutman, MD||National Institutes of Health (NIH)|