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

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.

Study Overview

• Status: Completed
• Conditions: Multi-drug Resistant Tuberculosis
• Intervention / Treatment: Other: Serum Vitamin D

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.

• Study Type: Observational
• Enrollment (Actual): 352

Contacts and Locations

Study Locations

• India
  • Maharashtra
    • Mumbai, Maharashtra, India, 400 018
      • Foundations for Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• 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

Description

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.

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Harvard School of Public Health (HSPH)
• Collaborators: Foundation for Medical Research; Municipal Corporation of Greater Mumbai, India

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 27, 2020
• Primary Completion (ACTUAL): December 17, 2020
• Study Completion (ACTUAL): December 17, 2020

Study Registration Dates

• First Submitted: April 7, 2020
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (ACTUAL): April 13, 2020

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2021
• Last Update Submitted That Met QC Criteria: February 24, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Vitamin D; Diet; Tuberculosis; Vitamin D deficiency; Latent tuberculosis infection; Multi-drug resistant tuberculosis; Extensively drug-resistant tuberculosis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Tuberculosis, Multidrug-Resistant; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: IRB19-0237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No