Vitamin D Supplementation in TB Prevention

Conditions

Latent Tuberculosis

Brief 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.

Davaasambuu Ganmaa, Stephanie Hemmings, David A. Jolliffe, Uyanga Buyanjargal, Gantsetseg Garmaa et al. (18 authors)

BMJ Open Sport & Exercise Medicine2024-09-014 citations

10.1136/bmjsem-2024-002018

Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial.

Ganmaa D, Khudyakov P, Buyanjargal U, Tserenkhuu E, Erdenenbaatar S, Achtai CE, Yansanjav N, Delgererekh B, Ankhbat M, Tsendjav E, Ochirbat B, Jargalsaikhan B, Enkhmaa D, Martineau AR.

2023-12-0113 citations

10.1016/s2213-8587(23)00317-0

Influence of Vitamin D Supplementation on Growth, Body Composition, and Pubertal Development Among School-aged Children in an Area With a High Prevalence of Vitamin D Deficiency

Davaasambuu Ganmaa, Sabri Bromage, Polyna Khudyakov, Sumiya Erdenenbaatar, Baigal Delgererekh et al. (6 authors)

JAMA Pediatrics2022-11-2841 citations

10.1001/jamapediatrics.2022.4581

Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease

Davaasambuu Ganmaa, Uyanga Buyanjargal, Xin Zhou, Gantsetseg Garmaa, Baigali Delgerekh et al. (23 authors)

New England Journal of Medicine2020-07-22179 citations

10.1056/nejmoa1915176

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.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

PREVENTION

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Intervention model description

Parallel assignment

Eligibility

Sex/Gender

ALL

Age

6 Years to 13 Years

Healthy volunteers

Yes

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 informed consent for child to participate in study

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 immunosuppressant or cytotoxic therapy, or vitamin D supplement \> 400IU / day 6. Plans to move away from study area within 3 years of enrolment

Design outcomes

Primary

Measure	Time frame	Description
Acquisition of latent tuberculosis infection	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

Measure	Time frame	Description
Body composition: impedance, impedance%, fat mass fat %, and fat-free mass	Three years	All participants
Spirometric lung volumes (FEV1 and FVC)	Three years	Sub-set of participants
Urinary metabolome profile	Three years	Sub-set of participants
Gut microbiome profile	Three years	Sub-set of participants
Control of asthma, allergic rhinitis and atopic dermatitis	Three years	Sub-sets of participants identified as having asthma, allergic rhinitis or atopic dermatitis at baseline
Incidence of active TB disease	Three years	All participants
Incidence of self-reported acute respiratory infection (upper, lower and both combined)	Three years	All participants
Incidence of acute respiratory infection requiring hospitalization	Three years	All participants
Incidence of acute respiratory infections requiring antibiotic treatment	Three years	All participants
Number of days off school (total number and number due to acute respiratory infection)	Three years	All participants
Incidence of acute asthma exacerbation requiring hospitalization	Three years	Sub-set of participants with asthma at baseline
Incidence of new asthma, allergic rhinitis and atopic dermatitis	Three years	Sub-sets of participants without asthma, allergic rhinitis or atopic dermatitis at baseline
Incidence of bone fracture	Three years	All participants
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)	Three years	All participants
Muscle strength: grip strength and long jump distance from standing	Three years	All participants
Serum 25-hydroxyvitamin D concentration	Three years	All participants
Bone mineral density at the radius	Three years	Sub-set of participants
Physical fitness (maximal oxygen consumption estimated from 20m shuttle run)	Three years	Sub-set of participants
Attention-related behavior scores (Connors III)	Three years	Sub-set of participants
Incidence of dental caries	Three years	Sub-set of participants
Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators	Three years	Sub-set of participants
Exam performance	Three years	Sub-set of participants
Self-reported pubertal development	Three years	Sub-set of participants

Other

Measure	Time frame	Description
Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB	Three years	Health economic analysis
Incidence of adverse events	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.
Heterogeneity of treatment effect among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype	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: 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).

Countries

Mongolia

Outcome results

None listed