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CompletedNCT02276755Updated Jul 16, 2020

Vitamin D Supplementation in TB Prevention

A Phase 3 interventional study of Cholecalciferol (vitamin D3) and Placebo in Latent Tuberculosis, sponsored by Harvard School of Public Health (HSPH). Completed at 1 site in Mongolia. Open to participants aged 6 Years to 13 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2020-07-16.

Sponsored by Harvard School of Public Health (HSPH) · Phase 3, Interventional, and Prevention

Phase
Phase 3
Study type
Interventional
Enrollment
8,851
Allocation
Randomized
Ages
6 Years to 13 Years
Sex
All
01

Study summary

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.

02

Conditions studied

  • Latent Tuberculosis

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03

In context

Latent Tuberculosis

199 studies on the registry are indexed under Latent Tuberculosis; 48 are open to participants now.

This study's enrollment of 8,851 is above the median of 300 across 110 interventional studies indexed under Latent Tuberculosis.

Browse Latent Tuberculosis studies →

Lead sponsor

Harvard School of Public Health (HSPH) is the lead sponsor of 154 studies on the registry; 10 are open to participants now.

Browse Harvard School of Public Health (HSPH) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
6 Years to 13 Years
Sexes eligible
All
Accepts healthy volunteers
Yes

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

  1. Chronic medical conditions
  2. Presence of LTBI on screening, as evidenced by a positive QFT-G
  3. Clinical signs of rickets, or diagnosis of any other condition requiring vitamin D supplementation
  4. Known primary hyperparathyroidism or sarcoidosis
  5. Taking or cytotoxic therapy, or vitamin D supplement > 400IU / day
  6. Plans to move away from study area within 3 years of enrolment
Terms in these criteria, in plain language(2)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

05

Study design

Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Quadruple (Participant, Care provider, Investigator, Outcomes assessor)
Enrollment
8,851 participants (actual)

Study arms

  • Active comparator
    Intervention: 1

    Dietary Supplement: Cholecalciferol (vitamin D3)

    Dietary Supplement: Cholecalciferol (vitamin D3)

  • Placebo comparator
    Placebo Comparator: 2

    Dietary Supplement: Placebo

    Other: Placebo

Interventions

  • Dietary supplementCholecalciferol (vitamin D3)

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

  • OtherPlacebo

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

06

What researchers measure

Primary outcomes

  1. Acquisition of latent tuberculosis infection

    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.

    Time frame: Three years

Secondary outcomes

  1. Incidence of active TB disease

    All participants

    Time frame: Three years

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

    All participants

    Time frame: Three years

  3. Incidence of acute respiratory infection requiring hospitalization

    All participants

    Time frame: Three years

  4. Incidence of acute respiratory infections requiring antibiotic treatment

    All participants

    Time frame: Three years

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

    All participants

    Time frame: Three years

  6. Incidence of acute asthma exacerbation requiring hospitalization

    Sub-set of participants with asthma at baseline

    Time frame: Three years

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

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

    Time frame: Three years

  8. Control of asthma, allergic rhinitis and atopic dermatitis

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

    Time frame: Three years

  9. Incidence of bone fracture

    All participants

    Time frame: Three years

  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)

    All participants

    Time frame: Three years

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

    All participants

    Time frame: Three years

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

    All participants

    Time frame: Three years

  13. Serum 25-hydroxyvitamin D concentration

    All participants

    Time frame: Three years

  14. Bone mineral density at the radius

    Sub-set of participants

    Time frame: Three years

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

    Sub-set of participants

    Time frame: Three years

  16. Attention-related behavior scores (Connors III)

    Sub-set of participants

    Time frame: Three years

  17. Incidence of dental caries

    Sub-set of participants

    Time frame: Three years

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

    Sub-set of participants

    Time frame: Three years

  19. Exam performance

    Sub-set of participants

    Time frame: Three years

  20. Self-reported pubertal development

    Sub-set of participants

    Time frame: Three years

  21. Spirometric lung volumes (FEV1 and FVC)

    Sub-set of participants

    Time frame: Three years

  22. Urinary metabolome profile

    Sub-set of participants

    Time frame: Three years

  23. Gut microbiome profile

    Sub-set of participants

    Time frame: Three years

Other outcomes

  1. Incidence of adverse events

    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.

    Time frame: Three years

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

    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: 1. An interaction term between baseline vitamin D status and allocation to vitamin D vs. placebo 2. An interaction term between estimated calcium intake and allocation to vitamin D vs. placebo 3. 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).

    Time frame: Three years

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

    Health economic analysis

    Time frame: Three years

07

Study locations

1 site
  • Mongolian Health Initiative
    Ulaanbaatar, Mongolia
08

References and documents

Publications

  • Ganmaa D, Uyanga B, Zhou X, Gantsetseg G, Delgerekh B, Enkhmaa D, Khulan D, Ariunzaya S, Sumiya E, Bolortuya B, Yanjmaa J, Enkhtsetseg T, Munkhzaya A, Tunsag M, Khudyakov P, Seddon JA, Marais BJ, Batbayar O, Erdenetuya G, Amarsaikhan B, Spiegelman D, Tsolmon J, Martineau AR. Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease. N Engl J Med. 2020 Jul 23;383(4):359-368. doi: 10.1056/NEJMoa1915176. PubMed 32706534 ↗

Study documents

PDFs hosted by the registry, ClinicalTrials.gov.

Individual participant data

Plan to share: Yes — IPD will be shared for purposes of meta-analysis, subject to approval from IRBs in Mongolia and the USA and terms of data sharing agreements.

Supporting information: Study protocol, Statistical analysis plan, Informed consent form, Clinical study report, Analytic code

Time frame: The items above will be shared following publication of trial reports.

Access criteria: IPD requests should be made to the Principal Investigator: gdavaasa@hsph.harvard.edu

09

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Ran from Sep 2015 to primary completion in Jun 2019, 45 months.

How these figures are worked out, and which studies are left out of them.

Registered
Oct 23, 2014
First posted
Oct 28, 2014
StartActual
Sep 2015
Primary completionActual
Jun 2019
CompletionActual
Jun 2020
Last update
Jul 16, 2020
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 16, 2020, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
10

Registry details

Key details

Study ID
NCT02276755
Lead sponsor
Harvard School of Public Health (HSPH)
Responsible party
Ganmaa Davaasambuu (Assistant Professor, Harvard School of Public Health (HSPH)) — Principal investigator
First posted
Oct 28, 2014
Start date
Sep 2015
Primary completion
Jun 2019
Completion
Jun 2020
Last update
Jul 16, 2020

Study contacts

Davaasambuu Ganmaa, MD PhD
principal investigator · Harvard School of Public Health (HSPH)

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jul 2020. You cannot join it, but the record below documents what was studied.

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