MDR-TB Free: Monitoring Adverse Effects, Utilizing Resources Optimally, Knowing Resistance Patterns, and Treatment Strategy

Post Date: 
2017-03-24
Clinical Site(s): 
Country: 
Summary: 

Purpose: To establish an observational cohort of MDR-TB cases and household contacts with accompanying biorepository at PD Hinduja National Hospital and Medical Research Centre

Primary Objectives:

  • Cohort A: To document participant outcomes including early treatment response, MDR-TB treatment-associated adverse events, mortality, and loss to follow-up.
  • Cohort B: To assess rates of prevalent and incident TB infection and disease in household contacts of MDR-TB cases.

    
Secondary Objectives:

Cohort A Secondary Objectives:

  1. To evaluate the impact of comorbid diseases including diabetes mellitus, prediabetes, HIV, COPD, smoking status, alcoholism, depression, quality of life, and malnutrition on treatment outcomes and TB treatment-associated adverse events.
  2. To assess the genotype-phenotype correlation among resistant TB isolates through MIC-based phenotypic drug susceptibility testing and next generation sequencing of TB isolates, including assessment of strain evolution, drug susceptibility pattern changes during treatment, and impact of strain on treatment outcomes.
  3. To derive pharmacokinetic parameters of second-line agents in participants receiving multidrug treatment regimens with particular attention to linezolid, clofazimine, high-dose moxifloxacin, aminoglycosides, and any new drugs that become available including bedaquiline and delamanid.
  4. To assess host biomarkers of treatment response and correlates of progression from exposure to TB disease using multiomics approaches (e.g. transcriptomics, metabolomics, cellular markers, and immunity- and inflammation-associated soluble biomarkers).
  5. To assess microbial markers of treatment response including smear and culture conversion, quantitative burden, and the time to conversion.
  6. To assess standard and novel imaging approaches to monitor treatment responses.
  7. To assess the impact of TB on the quality of life and mental health of subjects with MDR-TB, and in turn their impact on treatment adherence and outcomes.
  8. To assess host immune responses to and inflammation following TB exposure and TB treatment and correlate these responses with clinical outcomes.
  9. To ascertain true outcomes and self-reported barriers to treatment retention of MDR-TB participants lost to follow-up (>=2 consecutive months of missed visits) during treatment through prospective phone follow-up and/or home visits.
         

Cohort B Secondary Objectives:

  1. To evaluate the impact of comorbid diseases including diabetes mellitus, prediabetes, HIV, COPD, smoking status, alcoholism, depression, quality of life, and malnutrition on incident and prevalent TB among household contacts of MDR-TB cases.
  2. To assess the frequency with which household contacts of MDR-TB cases are found to have the same TB strain as the index case with whom they live.
  3. To assess biomarkers of incident TB and progression from exposure to TB disease using multiomics approaches (e.g. transcriptomics, metabolomics, cellular markers, and immunity- and inflammation-associated soluble biomarkers).
Collaborators: 
  • Christian Medical College (CMC) Vellore, Vellore, India
  • University of Massachusetts Medical School, Worcester, MA
  • Boston University School of Public Health, Boston, MA
  • LEPRA Society - Blue Peter Research Centre, Hyderabad, India
  • University of Texas Health Center, Tyler, TX
  • Institute of Bioinformatics, Bangalore, India