Case Control Study of Vitamin D Status and Adult Multidrug-resistant Pulmonary Tuberculosis in Maharashtra, India

Study Overview
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Brief Summary
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India has the highest incidence of and mortality from multi-drug resistant tuberculosis (MDR-TB) globally. Vitamin D status may be an important determinant of MDR-TB infection and treatment outcomes; however, observational evidence is insufficient to support its use as an adjunct therapy or prophylaxis. Using a case-control design, this study will evaluate the relationship between vitamin D status and active MDR-TB disease among adult outpatient pulmonary MDR-TB cases, household contact controls, and matched controls from the general population (non-household controls) in Mumbai, India. This study will also evaluate the cross-sectional association between vitamin D status and TB infection among household contact controls and non-household controls, and collect formative data in preparation for future randomized controlled trials of vitamin D in MDR-TB prevention and treatment in India.

Detailed Description
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To combat the substantial global burdens of TB and MDR-TB, novel treatment strategies and expanded prevention efforts are critical. Although vitamin D supplementation shows promise in both of these areas, additional observational evidence is needed to support future randomized clinical trials. This case-control study in Mumbai, India will clarify associations between vitamin D status, active MDR-TB disease and TB infection to expand the evidence-base and inform the design of future trials of vitamin D supplementation for use in MDR-TB infection. This study will assess vitamin D status, diet, and anthropometry among adult outpatient MDR-TB cases and controls in Mumbai, India and assess TB infection among controls. The specific aims are: 1) evaluate the association between vitamin D status and active MDR-TB infection; 2) evaluate the association between vitamin D status and TB infection among controls; 3) collect formative data to inform the design of future randomized clinical trials evaluating vitamin D supplementation and other interventions in MDR-TB treatment and prevention. To fulfill the first aim, a case-control study will be conducted comparing vitamin D status between pulmonary MDR-TB cases (including extensively drug-resistant (XDR) and pre-XDR cases) and two sets of controls: 1) household controls (recruited from the cases' household contacts) and 2) non-household controls (recruited from non-respiratory departments of local hospitals). The second aim will involve a cross-sectional study among controls assessing the association between vitamin D status and TB infection using QuantiFERON-TB (QFT-TB) interferon-gamma release assays.

Official Title
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Case Control Study of Vitamin D Status and Adult Multidrug-resistant Pulmonary Tuberculosis in Maharashtra, India

Conditions
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Multi-drug Resistant Tuberculosis

Intervention / Treatment
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* Other: Serum Vitamin D


Participation Criteria
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Eligibility Criteria
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Inclusion criteria for cases: Currently receiving outpatient treatment for MDR-TB according to standard of care (including new cases and those who have been on treatment for no more than one month) Residence in Mumbai M/E, M/W or H/E ward for at least six months 18-60 years old Permanently living with at least two eligible controls Confirmation that they have disclosed their TB status to household and will allow inclusion of their household members in the study Inclusion criteria for household contact controls: Was a permanent member of the index case's household for at least one year prior to the case's DR TB diagnosis No symptoms of active TB disease Residence in Mumbai M/E, M/W or H/E ward for at least six months 18-60 years old Inclusion criteria for non-household controls: 18 - 60 years of age Residence in Mumbai M/E, M/W or H/E ward for at least six months No symptoms of active TB disease No history of household contact with a TB patient in last 2 years Exclusion criterion for both cases and controls: • Pregnancy.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult outpatient pulmonary MDR-TB patients<br> | Other: Serum Vitamin D<br>* Primary exposure assessed will be serum vitamin D (25(OH)D). Diet will also be assessed via Food Frequency Questionnaire.<br>* Other names: Diet;|
| Household contact controls<br> | Other: Serum Vitamin D<br>* Primary exposure assessed will be serum vitamin D (25(OH)D). Diet will also be assessed via Food Frequency Questionnaire.<br>* Other names: Diet;|
| Non-household contact controls<br> | Other: Serum Vitamin D<br>* Primary exposure assessed will be serum vitamin D (25(OH)D). Diet will also be assessed via Food Frequency Questionnaire.<br>* Other names: Diet;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adult pulmonary multi-drug resistant tuberculosis | Defined by the Guidelines on Programmatic Management of Drug-Resistant TB in India. Includes cases with MDR-TB (resistant to both isoniazid and rifampicin with or without resistance to other first-line drugs), pre-XDR-TB(MDR-TB patients with additional resistance to any/all fluoroquinolones or any/all second-line drugs, or XDR-TB (MDR-TB patients who are additionally resistant to at least one fluoroquinolone and a second-line drug). | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Latent TB infection among controls | Assessed using QuantiFERON-TB (QFT-TB) interferon-gamma release assays. | Baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Multi-drug resistant tuberculosis, Extensively drug-resistant tuberculosis, Vitamin D, Vitamin D deficiency, Tuberculosis, Latent tuberculosis infection, Diet