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

President and Fellows of Harvard College

Status: Completed

Conditions: Multi-drug Resistant Tuberculosis

Treatments: Other: Serum Vitamin D

Study type: Observational

Funder types: Other

Identifiers

NCT04342598

IRB19-0237

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 352 patients

Sex: All

Ages: 18 to 60 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

1. 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

2. 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

3. 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.

Trial design

352 participants in 3 patient groups

Adult outpatient pulmonary MDR-TB patients

Treatment:

Other: Serum Vitamin D

Household contact controls

Treatment:

Other: Serum Vitamin D

Non-household contact controls

Treatment:

Other: Serum Vitamin D