Vitamin D Supplementation in TB Prevention
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Intervention: 1 Dietary Supplement: Cholecalciferol (vitamin D3) |
Dietary Supplement: Cholecalciferol (vitamin D3)
14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA).
|
| Placebo Comparator: Placebo Comparator: 2 Dietary Supplement: Placebo |
Other: Placebo
Placebo group will receive placebo (Tishcon, USA) weekly.
|
Outcome Measures
Primary Outcome Measures
- 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
- 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
- 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
- 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
- Body composition: impedance, impedance%, fat mass fat %, and fat-free mass [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
- 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
Other Outcome Measures
- 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: 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).
- Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB [Three years]
Health economic analysis
Eligibility Criteria
Criteria
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
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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
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mongolian Health Initiative | Ulaanbaatar | Mongolia |
Sponsors and Collaborators
- Harvard School of Public Health (HSPH)
Investigators
- Principal Investigator: Davaasambuu Ganmaa, MD PhD, Harvard School of Public Health (HSPH)
Study Documents (Full-Text)
More Information
Publications
None provided.- 140513