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Completed

NCT Number: NCT02276755

Vitamin D Supplementation in TB Prevention

The goal of this clinical trial is to determine whether vitamin D supplementation reduces risk of acquiring latent tuberculosis infection (LTBI) in school age children in Mongolia. The investigators hypothesize that (1) vitamin D supplementation will reduce risk of acquisition of LTBI, (2) vitamin D supplementation will safely reduce risk of developing active TB and improve other secondary efficacy outcomes, and (3) children with the lowest vitamin D status at baseline will gain most from the intervention.

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Key information

Conditions

Latent Tuberculosis Actinomycetales Infections Bacterial Infections Bacterial Infections and Mycoses Gram-Positive Bacterial Infections Infections Latent Infection Mycobacterium Infections Tuberculosis

Age range

6 year–13 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

Mongolian Health Initiative

Ulaanbaatar, Mongolia

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Boys or girls aged 6 to 13 years at enrolment
  • Attending participating school in Ulaanbaatar at enrolment
  • Child gives informed assent to participate in the study
  • Child's parent/legal guardian gives informed consent for child to participate in study

Exclusion criteria

  • Chronic medical conditions
  • Presence of LTBI on screening, as evidenced by a positive QFT-G
  • Clinical signs of rickets, or diagnosis of any other condition requiring vitamin D supplementation
  • Known primary hyperparathyroidism or sarcoidosis
  • Taking immunosuppressant or cytotoxic therapy, or vitamin D supplement > 400IU / day
  • Plans to move away from study area within 3 years of enrolment

Treatment and study plan

Cholecalciferol (vitamin D3)

Dietary Supplement

14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA).

Placebo

Other

Placebo group will receive placebo (Tishcon, USA) weekly.

Primary outcomes

  1. Acquisition of latent tuberculosis infection

    Time frame: Three years

    The proportion of children who acquire LTBI during the 3 year period will be compared for children randomized to vitamin D3 vs. placebo using the Mantel-Haenszel risk ratio, stratified by school of attendance. The primary analysis will compare the proportion of children who are QuantiFERON-positive at the 0.35 IU/ml IFN-gamma threshold at the end of the study. Exploratory analyses will compare the proportion of children who are positive at the 4.0 IU/ml IFN-gamma threshold (denoting stable conversion) and mean / median antigen-stimulated IFN-gamma concentration analyzed as a continuous variable.

Secondary outcomes

  1. Incidence of active TB disease

    Time frame: Three years

    All participants

  2. Incidence of self-reported acute respiratory infection (upper, lower and both combined)

    Time frame: Three years

    All participants

  3. Incidence of acute respiratory infection requiring hospitalization

    Time frame: Three years

    All participants

  4. Incidence of acute respiratory infections requiring antibiotic treatment

    Time frame: Three years

    All participants

  5. Number of days off school (total number and number due to acute respiratory infection)

    Time frame: Three years

    All participants

  6. Incidence of acute asthma exacerbation requiring hospitalization

    Time frame: Three years

    Sub-set of participants with asthma at baseline

  7. Incidence of new asthma, allergic rhinitis and atopic dermatitis

    Time frame: Three years

    Sub-sets of participants without asthma, allergic rhinitis or atopic dermatitis at baseline

  8. Control of asthma, allergic rhinitis and atopic dermatitis

    Time frame: Three years

    Sub-sets of participants identified as having asthma, allergic rhinitis or atopic dermatitis at baseline

  9. Incidence of bone fracture

    Time frame: Three years

    All participants

  10. Anthropometric outcomes (z-scores for height-for-age, weight-for-age, weight-for-height, body mass index-for-age, and waist circumference and waist-to-height ratio)

    Time frame: Three years

    All participants

  11. Body composition: impedance, impedance%, fat mass fat %, and fat-free mass

    Time frame: Three years

    All participants

  12. Muscle strength: grip strength and long jump distance from standing

    Time frame: Three years

    All participants

  13. Serum 25-hydroxyvitamin D concentration

    Time frame: Three years

    All participants

  14. Bone mineral density at the radius

    Time frame: Three years

    Sub-set of participants

  15. Physical fitness (maximal oxygen consumption estimated from 20m shuttle run)

    Time frame: Three years

    Sub-set of participants

  16. Attention-related behavior scores (Connors III)

    Time frame: Three years

    Sub-set of participants

  17. Incidence of dental caries

    Time frame: Three years

    Sub-set of participants

  18. Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators

    Time frame: Three years

    Sub-set of participants

  19. Exam performance

    Time frame: Three years

    Sub-set of participants

  20. Self-reported pubertal development

    Time frame: Three years

    Sub-set of participants

  21. Spirometric lung volumes (FEV1 and FVC)

    Time frame: Three years

    Sub-set of participants

  22. Urinary metabolome profile

    Time frame: Three years

    Sub-set of participants

  23. Gut microbiome profile

    Time frame: Three years

    Sub-set of participants

Other outcomes

  1. Incidence of adverse events

    Time frame: Three years

    The proportion of participants experiencing death, one or more serious adverse events of any cause or one or more potential adverse reactions (hypercalcemia, hypercalciuria and hypervitaminosis D) will be compared between arms.

  2. Heterogeneity of treatment effect among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype

    Time frame: Three years

    Heterogeneity of treatment effect will be examined among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype for primary and secondary outcomes. This will be done by repeating efficacy analyses to include:

    • An interaction term between baseline vitamin D status and allocation to vitamin D vs. placebo
    • An interaction term between estimated calcium intake and allocation to vitamin D vs. placebo
    • An interaction term between vitamin D pathway genotype and allocation to vitamin D vs. placebo.

    For genetic analyses, DNA will be extracted from participants' stored whole blood, and typed for a panel of candidate single nucleotide polymorphisms (SNPs) in genes influencing vitamin D metabolism (e.g. CYP2R1, CYP27B1, CYP24A1), transport (e.g. DBP) and signalling (e.g. VDR).

  3. Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB

    Time frame: Three years

    Health economic analysis

Sponsors and collaborators

Lead sponsor

Harvard School of Public Health (HSPH)

Other

Registry information

Official study title

Vitamin D in TB Prevention in School Age Children

Important dates

Study start
2015
Primary completion
2019
Study completion
2020
First posted
Oct 28, 2014
Registry last updated
Jul 16, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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