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
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures
研究概览
简要总结
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.
详细描述
Study Design: This is a cross-sectional study to identify individuals with LTBI and coinfections/comorbidities: malnutrition; DM; and helminth infections. Individuals will first be evaluated clinically for symptoms of active TB. Individuals with symptoms of active TB will be excluded from the study and referred for treatment. Individuals who are asymptomatic for active TB will be screened for LTBI by interferon gamma (IFNγ) release assay (IGRA) and clinically assessed for malnutrition (by body mass index [BMI]), evaluated for DM status (by hemoglobin A1c [HbA1c] levels), and evaluated for helminth infection (by serology and stool quantitative polymerase chain reaction [qPCR]).
Individuals who are eligible will be assigned to one of six study groups based on LTBI status and presence of coinfections/comorbidities. Participants will have an additional study visit within 6 months of screening for clinical assessment and provide blood (30 ml), urine, and stool samples for experimental studies and storage for future research. Key research evaluations will include gene expression analyses and immunophenotyping on blood samples.
Sample Size:
Primary Objective: N=5000
Secondary Objective: N=300; n=50 for each of the following groups:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 14 Years 至 65 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures
时间窗: 6 months
Prevalence of malnutrition, DM and helminth infections in LTBI individuals and their effects on biosignatures
次要结局
未报告次要终点