Clinical trial NCT02276755: Vitamin D Supplementation in TB Prevention
Official title: Vitamin D in TB Prevention in School Age Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Latent Tuberculosis
Lead sponsor: Harvard School of Public Health (HSPH)
Sponsor class: OTHER
First posted: 2014-10-28
Enrollment: 8851
Sex: ALL
Minimum age (years): 6
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel assignment
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Acquisition of latent tuberculosis infection
timeFrame: Three years
Secondary outcomes:
measure: Incidence of active TB disease
timeFrame: Three years
measure: Incidence of self-reported acute respiratory infection (upper, lower and both combined)
timeFrame: Three years
measure: Incidence of acute respiratory infection requiring hospitalization
timeFrame: Three years
measure: Incidence of acute respiratory infections requiring antibiotic treatment
timeFrame: Three years
measure: Number of days off school (total number and number due to acute respiratory infection)
timeFrame: Three years
measure: Incidence of acute asthma exacerbation requiring hospitalization
timeFrame: Three years
measure: Incidence of new asthma, allergic rhinitis and atopic dermatitis
timeFrame: Three years
measure: Control of asthma, allergic rhinitis and atopic dermatitis
timeFrame: Three years
measure: Incidence of bone fracture
timeFrame: Three years
measure: 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)
timeFrame: Three years
measure: Body composition: impedance, impedance%, fat mass fat %, and fat-free mass
timeFrame: Three years
measure: Muscle strength: grip strength and long jump distance from standing
timeFrame: Three years
measure: Serum 25-hydroxyvitamin D concentration
timeFrame: Three years
measure: Bone mineral density at the radius
timeFrame: Three years
measure: Physical fitness (maximal oxygen consumption estimated from 20m shuttle run)
timeFrame: Three years
measure: Attention-related behavior scores (Connors III)
timeFrame: Three years
measure: Incidence of dental caries
timeFrame: Three years
measure: Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators
timeFrame: Three years
measure: Exam performance
timeFrame: Three years
measure: Self-reported pubertal development
timeFrame: Three years
measure: Spirometric lung volumes (FEV1 and FVC)
timeFrame: Three years
measure: Urinary metabolome profile
timeFrame: Three years
measure: Gut microbiome profile
timeFrame: Three years
Other outcomes:
measure: Incidence of adverse events
timeFrame: Three years
measure: Heterogeneity of treatment effect among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype
timeFrame: Three years
measure: Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB
timeFrame: Three years
Locations:
city: Ulaanbaatar
country: Mongolia
facility: Mongolian Health Initiative
Study officials:
affiliation: Harvard School of Public Health (HSPH)
name: Davaasambuu Ganmaa, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.