Vitamin D Supplementation in TB Prevention

Phase 3

Completed

• Conditions: Latent Tuberculosis
• Interventions: Other: Placebo; Dietary Supplement: Cholecalciferol (vitamin D3)

• Registration Number: NCT02276755
• Lead Sponsor: Harvard School of Public Health (HSPH)

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2014-10-23
• Study First Submitted QC: 2014-10-27
• Study First Posted: 2014-10-28
• Study Start: 2015-09
• Primary Completion: 2019-06
• Study Completion: 2020-06
• Status Verified: 2020-07
• Last Update Submitted: 2020-07-14
• Last Update Posted: 2020-07-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 8851

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Comparator: 2	Placebo	Dietary Supplement: Placebo
Intervention: 1	Cholecalciferol (vitamin D3)	Dietary Supplement: Cholecalciferol (vitamin D3)

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Incidence of active TB disease	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 respiratory infection requiring hospitalization	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
Muscle strength: grip strength and long jump distance from standing	Three years	All participants
Exam performance	Three years	Sub-set of participants
Self-reported pubertal development	Three years	Sub-set of participants
Urinary metabolome profile	Three years	Sub-set of participants
Gut microbiome profile	Three years	Sub-set of participants
Incidence of acute respiratory infections requiring antibiotic treatment	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
Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators	Three years	Sub-set of participants
Incidence of self-reported acute respiratory infection (upper, lower and both combined)	Three years	All participants
Body composition: impedance, impedance%, fat mass fat %, and fat-free mass	Three years	All 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
Spirometric lung volumes (FEV1 and FVC)	Three years	Sub-set of participants
Serum 25-hydroxyvitamin D concentration	Three years	All 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 bone fracture	Three years	All participants
Bone mineral density at the radius	Three years	Sub-set of participants

Trial Locations

Locations (1)

Mongolian Health Initiative; 🇲🇳 Ulaanbaatar, Mongolia