Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Intervention: 1 | Active Comparator | Dietary Supplement: Cholecalciferol (vitamin D3) |
|
| Placebo Comparator: 2 | Placebo Comparator | Dietary Supplement: Placebo |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cholecalciferol (vitamin D3) | Dietary Supplement | 14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA). |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Three years |
| Measure | Description | Time Frame |
|---|---|---|
| Incidence of active TB disease | All participants | Three years |
| Incidence of self-reported acute respiratory infection (upper, lower and both combined) | All participants |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Three years |
| Heterogeneity of treatment effect among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Davaasambuu Ganmaa, MD PhD | Harvard School of Public Health (HSPH) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Mongolian Health Initiative | Ulaanbaatar | Mongolia |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 39345833 | Derived | Ganmaa D, Hemmings S, Jolliffe DA, Buyanjargal U, Garmaa G, Adiya U, Tumurbaatar T, Dorjnamjil K, Tserenkhuu E, Erdenenbaatar S, Tsendjav E, Enkhamgalan N, Achtai CE, Talhaasuren Y, Byambasuren T, Ganbaatar E, Purevdorj E, Martineau AR. Influence of vitamin D supplementation on muscle strength and exercise capacity in Mongolian schoolchildren: secondary outcomes from a randomised controlled trial. BMJ Open Sport Exerc Med. 2024 Sep 26;10(3):e002018. doi: 10.1136/bmjsem-2024-002018. eCollection 2024. | |
| 38048799 |
Not provided
Not provided
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.
The items above will be shared following publication of trial reports.
IPD requests should be made to the Principal Investigator: gdavaasa@hsph.harvard.edu
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Apr 25, 2019 | May 22, 2019 | Prot_SAP_000.pdf |
Not provided
| ID | Term |
|---|---|
| D055985 | Latent Tuberculosis |
| ID | Term |
|---|---|
| D014376 | Tuberculosis |
| D009164 | Mycobacterium Infections |
| D000193 | Actinomycetales Infections |
| D016908 | Gram-Positive Bacterial Infections |
Not provided
Not provided
| ID | Term |
|---|---|
| D002762 | Cholecalciferol |
| ID | Term |
|---|---|
| D002782 | Cholestenes |
| D002776 | Cholestanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
Not provided
Not provided
Parallel assignment
Not provided
Not provided
Not provided
| Placebo | Other | Placebo group will receive placebo (Tishcon, USA) weekly. |
|
| Three years |
| Incidence of acute respiratory infection requiring hospitalization | All participants | Three years |
| Incidence of acute respiratory infections requiring antibiotic treatment | All participants | Three years |
| Number of days off school (total number and number due to acute respiratory infection) | All participants | Three years |
| Incidence of acute asthma exacerbation requiring hospitalization | Sub-set of participants with asthma at baseline | Three years |
| Incidence of new asthma, allergic rhinitis and atopic dermatitis | Sub-sets of participants without asthma, allergic rhinitis or atopic dermatitis at baseline | Three years |
| Control of asthma, allergic rhinitis and atopic dermatitis | Sub-sets of participants identified as having asthma, allergic rhinitis or atopic dermatitis at baseline | Three years |
| Incidence of bone fracture | All participants | Three years |
| 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 | Three years |
| Body composition: impedance, impedance%, fat mass fat %, and fat-free mass | All participants | Three years |
| Muscle strength: grip strength and long jump distance from standing | All participants | Three years |
| Serum 25-hydroxyvitamin D concentration | All participants | Three years |
| Bone mineral density at the radius | Sub-set of participants | Three years |
| Physical fitness (maximal oxygen consumption estimated from 20m shuttle run) | Sub-set of participants | Three years |
| Attention-related behavior scores (Connors III) | Sub-set of participants | Three years |
| Incidence of dental caries | Sub-set of participants | Three years |
| Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators | Sub-set of participants | Three years |
| Exam performance | Sub-set of participants | Three years |
| Self-reported pubertal development | Sub-set of participants | Three years |
| Spirometric lung volumes (FEV1 and FVC) | Sub-set of participants | Three years |
| Urinary metabolome profile | Sub-set of participants | Three years |
| Gut microbiome profile | Sub-set of participants | 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:
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). |
| Three years |
| Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB | Health economic analysis | Three years |
| Derived |
| 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. Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2024 Jan;12(1):29-38. doi: 10.1016/S2213-8587(23)00317-0. Epub 2023 Dec 1. |
| 36441522 | Derived | Ganmaa D, Bromage S, Khudyakov P, Erdenenbaatar S, Delgererekh B, Martineau AR. 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: A Randomized Clinical Trial. JAMA Pediatr. 2023 Jan 1;177(1):32-41. doi: 10.1001/jamapediatrics.2022.4581. |
| 32706534 | Derived | 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. |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
| D007239 | Infections |
| D000085343 | Latent Infection |
| D011083 |
| Polycyclic Compounds |
| D013261 | Sterols |
| D014807 | Vitamin D |
| D012632 | Secosteroids |
| D008563 | Membrane Lipids |
| D008055 | Lipids |