Comorbidities and Coinfections in Latent TB

NCT04642755 | Recruiting DMC

• 2 other identifiers: 2020005AI001065-08
• Study Type: observational
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Latent Tuberculosis; Diabete Mellitus; Malnutrition; Helminth Infection

Outcome Measures

Primary Outcomes (1)

• Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures

  Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures

  6 months

Study Arms (6)

Group 1

LTBI+ and severe to moderate malnutrition

Group 2

LTBI+ and uncontrolled DM

Group 3

LTBI+ and helminth infection

Group 4

LTBI+ with more than one of the above conditions (severe to moderate malnutrition, DM, helminth infection)

Group 5

"Healthy" LTBI+ controls who are negative for all of the above conditions (severe to moderate malnutrition, DM, helminth infection)

Group 6

Healthy LTBI negative controls with none of the above conditions (severe to moderate malnutrition, DM, helminth infection).

Eligibility Criteria

• Age: 14 Years - 65 Years
• Sex: all
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

The screening phase of this study will be a community-based study in South India. Participants will be recruited from villages in the Kancheepuram District, where approximately 50% of the adult population tests positive for LTBI by IGRA based on our previous study (unpublished data). We also anticipate based on our previous study that the percentage of the adult population positive for malnutrition is 35%, for DM is 20%, and for helminth infection is 20% (unpublished data).

You may qualify if:

• Screening Phase:
• Individuals who meet the following criteria are eligible to participate in the screening phase:
• Aged 14 to 65 years.
• Willingness to provide blood, urine, and stool samples for examination.
• Willingness to have samples and data stored.
• Able to provide informed consent.
• Study Phase:
• Individuals are eligible for the study phase if they meet the requirements for one of the study groups, as follows:
• LTBI+ and severe to moderate malnutrition (BMI \<17 kg/m2);
• LTBI+ and uncontrolled DM (HbA1c \>8%);
• LTBI+ and helminth infection (positive stool qPCR and/or serology);
• LTBI+ with more than one of the conditions defined in groups 1-3;
• "healthy" LTBI+ controls who are negative for all of the above conditions; and
• healthy LTBI negative controls with none of the above conditions.

You may not qualify if:

• Screening Phase:
• Pulmonary symptoms suggestive of TB (cough \>2 weeks in duration and/or intermittent fever \>1 week in duration and/or hemoptysis).
• Two IGRA tests with indeterminate results (mitogen values \<10 IU).
• Study Phase:
• Pulmonary symptoms suggestive of TB (cough \>2 weeks in duration and/or intermittent fever \>1 week in duration and/or hemoptysis).
• Pregnant or lactating women.
• Previous treatment for LTBI.
• Anemia with hemoglobin \<8 g/dl (evaluated at the screening phase visit).
• For LTBI+ participants, clinically indicated chest X-ray positive for pulmonary TB.
• For malnourished participants, clinically indicated abdominal ultrasound positive for abdominal TB.
• Known documented cases of cancer, acquired immune deficiency syndrome, or other immunosuppressive illness.
• History of any other illness or condition which, in the investigator's judgment, may substantially increase the risk associated with the participant's participation in the protocol, or compromise the scientific objectives.

Sponsors & Collaborators

• Tuberculosis Research Centre, India: lead
• National Institutes of Health (NIH): collaborator

Study Sites (1)

National Institute for Research in Tuberculosis

Chennai, Tamil Nadu, 600031, India

RECRUITING

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.

MeSH Terms

Conditions

Latent Tuberculosis; Diabetes Mellitus; Malnutrition; Trematode Infections

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Nutrition Disorders; Helminthiasis; Parasitic Diseases

Study Officials

• Subash Babu, MBBS, PhD

  National Institute for Research in Tuberculosis

  PRINCIPAL INVESTIGATOR

• Thomas B Nutman, MD

  National Institutes of Health (NIH)

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Subash Babu, MBBS, PhD

CONTACT

044-28369711; sbabu@icerindia.org

Pradeep Menon, MBBS,DPM,MPH

CONTACT

9444294262; menonpa@nirt.res.in

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: CROSS SECTIONAL
• Target Duration: 6 Months
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 18, 2020
• First Posted: November 24, 2020
• Study Start: April 19, 2021
• Primary Completion: March 1, 2026
• Study Completion: March 1, 2026
• Last Updated: November 22, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

IN (1)