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The Influence of Malnutrition, Diabetes Mellitus, and Helminth Infections on Biosignatures in Latent Tuberculosis in a South Indian Population

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04526613
Recruitment Status : Active, not recruiting
First Posted : August 26, 2020
Last Update Posted : September 14, 2022
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) )

Brief Summary:

About 2 billion people worldwide are infected with tuberculosis (TB). Ninety percent of those people have latent TB infection (LTBI). Risk factors like malnutrition, diabetes mellitus (DM), and helminth infection can affect the development of active TB. Researchers want to study LTBI individuals with these issues to see how they may contribute to a person s higher risk for developing active TB. This study will take place in Chennai, India.

Objective:

To estimate the prevalence of malnutrition, DM, and helminth infections in people with LTBI.

Eligibility:

People age 14 65 with or without LTBI.

Design:

Participants will be screened with a medical history and physical exam focused on symptoms of active TB. Those who have TB symptoms will not take part in the study. Those who do not have TB symptoms will have a physical exam with vital signs, height, and weight. They will give blood and stool samples.

Participants will be assigned to 1 of 6 groups. They will repeat some of the screening tests. They will give urine samples. Some groups will have a chest X-ray. Some groups will have an ultrasound of the abdomen.

Participants will complete a survey about their history of smoking and drug and alcohol use.

Participants will have data collected about their nutritional status and body composition. Their skinfold thickness, ratio of waist/hip circumference, and grip strength will be measured.

Participants with DM, malnutrition, or helminth infection will be given standard of care or referred for follow-up treatment.

Participation will last up to 6 months.

...


Condition or disease
Mycobacterium Tuberculosis LTBI (Latent TB Infection) Malnutrition Diabetes Mellitus Helminth Infections

Detailed Description:

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.

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Study Type : Observational
Actual Enrollment : 626 participants
Observational Model: Cohort
Time Perspective: Prospective
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
Actual Study Start Date : April 19, 2021
Estimated Primary Completion Date : June 25, 2025
Estimated Study Completion Date : June 25, 2025


Group/Cohort
'healthy' LTBI+ controls who are negative for all of the conditions
'healthy' LTBI+ controls who are negative for all of the listed conditions
healthy LTBI negative controls with none of the above conditio
healthy LTBI negative controls with none of the above conditions
LTBI+ and helminth infection (positive stool qPCR and/or serol
LTBI+ and helminth infection (positive stool qPCR and/or serology)
LTBI+ and severe to moderate malnutrition (BMI <17 kg/m2)
LTBI+ and severe to moderate malnutrition (BMI <17 kg/m2)
LTBI+ and uncontrolled DM (HbA1c >8%)
LTBI+ and uncontrolled DM (HbA1c >8%)
LTBI+ with more than one of the conditions defined in groups 1
LTBI+ with more than one of the conditions defined in groups 1-3



Primary Outcome Measures :
  1. Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures [ Time Frame: Study Phase visit ]
    Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   14 Years to 65 Years   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Participants will be recruited from villages in the Kancheepuram District in south India. The census in villages in the Kancheepuram District is updated annually by local health workers employed by the Department of Public Health and the field teams of the NIRT in Chennai, India. The villages will be chosen in consultation with the Department of Public Health in Tamil Nadu.
Criteria
  • PARTICIPANT INCLUSION CRITERIA (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.

PARTICIPANT EXCLUSION CRITERIA (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).

PARTICIPANT INCLUSION CRITERIA (Study Phase)

Individuals are eligible for the study phase if they meet the requirements for one of the study groups, as follows:

  1. LTBI+ and severe to moderate malnutrition (BMI <17 kg/m2);
  2. LTBI+ and uncontrolled DM (HbA1c >8%);
  3. LTBI+ and helminth infection (positive stool qPCR and/or serology);
  4. LTBI+ with more than one of the conditions defined in groups 1 3;
  5. healthy LTBI+ controls who are negative for all of the above conditions; and
  6. healthy LTBI-negative controls with none of the above conditions.

PARTICIPANT EXCLUSION CRITERIA (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.

Information from the National Library of Medicine

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): NCT04526613


Locations
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India
National Institute for Research In Tuberculosis, International Centers for Exel
Chennai, India
Sponsors and Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
Investigators
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Principal Investigator: Thomas B Nutman, M.D. National Institute of Allergy and Infectious Diseases (NIAID)
Publications:
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Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT04526613    
Other Study ID Numbers: 999920144
20-I-N144
First Posted: August 26, 2020    Key Record Dates
Last Update Posted: September 14, 2022
Last Verified: September 6, 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: .This is a sample/data collection study to estimate the prevalence of malnutrition. DM and helminth infections in LBTI subjects. There is no plan to share individual participant data

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Allergy and Infectious Diseases (NIAID) ):
MALNUTRITION
Diabetes Mellitus
Helminth Infections
Pathogenesis
Immunological Assays
Additional relevant MeSH terms:
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Infections
Communicable Diseases
Tuberculosis
Latent Tuberculosis
Helminthiasis
Diabetes Mellitus
Malnutrition
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Disease Attributes
Pathologic Processes
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Bacterial Infections and Mycoses
Nutrition Disorders
Latent Infection
Parasitic Diseases