Clinical trial NCT04342598: Case Control Study of Vitamin D Status and Adult Multidrug-resistant Pulmonary Tuberculosis in Maharashtra, India
Official title: Case Control Study of Vitamin D Status and Adult Multidrug-resistant Pulmonary Tuberculosis in Maharashtra, India
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Multi-drug Resistant Tuberculosis
Keywords: Multi-drug resistant tuberculosis
Extensively drug-resistant tuberculosis
Vitamin D
Vitamin D deficiency
Tuberculosis
Latent tuberculosis infection
Diet
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
Collaborators: name: Foundation for Medical Research
name: Municipal Corporation of Greater Mumbai, India
First posted: 2020-04-13
Enrollment: 352
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Adult pulmonary outpatient MDR-TB cases, household contact controls and non-household controls residing in Mumbai in Maharashtra state, India

Brief summary: 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: 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.

Eligibility 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.

Primary outcomes:
measure: Adult pulmonary multi-drug resistant tuberculosis
timeFrame: Baseline
Secondary outcomes:
measure: Latent TB infection among controls
timeFrame: Baseline
Other outcomes:
Locations:
city: Mumbai
country: India
facility: Foundations for Medical Research
state: Maharashtra
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Wafaie W Fawzi, MBBS, MPH, MS, DrPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Mistry N, Hemler EC, Dholakia Y, Bromage S, Shukla A, Dev P, Govekar L, Tipre P, Shah D, Keshavjee SA, Fawzi WW. Protocol for a case-control study of vitamin D status, adult multidrug-resistant tuberculosis disease and tuberculosis infection in Mumbai, India. BMJ Open. 2020 Nov 12;10(11):e039935. doi: 10.1136/bmjopen-2020-039935.