Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren

Study Overview
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Brief Summary
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The investigators will conduct a n=5,400 Phase 3, double-blind, individually randomised placebo-controlled clinical trial of 5 years' duration in primary schools in City of Cape Town Metropolitan Municipality, Western Cape Province, Republic of South Africa. The primary objective of the trial is to determine whether a weekly oral dose of 0.25 mg (10,000 IU) vitamin D3, administered for three years, reduces risk of acquisition of latent tuberculosis infection (LTBI) in Cape Town primary schoolchildren. Statistical analysis will be performed on an intention-to-treat basis to compare acquisition of LTBI in intervention vs. control arms during three-year follow-up. The primary analysis will be logistic regression with presence/absence of LTBI at follow-up as the outcome, adjusted for a random effect of school of attendance.

Official Title
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Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren

Conditions
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Latent Tuberculosis

Intervention / Treatment
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* Dietary Supplement: Cholecalciferol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Pupil enrolled in Grades 1-4 of participating primary schools Age 6-11 years at enrolment Pupil gives written informed assent to participate in main trial Pupil's parent / legal guardian gives informed consent for pupil to participate in main trial Exclusion Criteria: Age ≤5 years or ≥12 years at enrolment Previous positive Interferon-Gamma Release Assay (IGRA) or Mantoux test Previous treatment for LTBI or active TB Clinical signs of rickets History of myalgia on walking Inability to rise unaided from squatting position Taking supplemental vitamin D at a dose >400 IU daily or equivalent in the previous month Diagnosis of any chronic illness other than asthma Suspected HIV infection in child with parent or legal guardian declining to have child HIV-tested Use of any regular medication other than asthma medication Plans to move away from study area within 3 years of enrolment Unable to swallow one placebo softgel with ease Positive Quantiferon-TB Gold Plus test at screening

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 11 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intervention<br>Softgel capsule containing 10,000 IU (250 micrograms) cholecalciferol (vitamin D3) to be taken orally once per week for 3 years | Dietary Supplement: Cholecalciferol<br>* Weekly oral softgel capsule containing 10,000 IU (250 micrograms) cholecalciferol (vitamin D3)<br>* Other names: Vitamin D3;|
| Placebo Comparator: Placebo<br>Softgel capsule of identical taste and appearance to active comparator, but containing no cholecalciferol, to be taken orally once per week for 3 years | Other: Placebo<br>* Weekly oral placebo softgel capsule<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acquisition of latent tuberculosis infection |  | 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of active tuberculosis (TB) |  | 3 years | 
| Incidence of acute respiratory infection |  | 3 years | 
| Incidence of acute asthma exacerbation |  | 3 years | 
| Incidence and control of asthma, allergic rhinitis and atopic dermatitis |  | 3 years | 
| Incidence of bone fracture |  | 3 years | 
| Anthropometric outcomes (weight, height, body mass index, waist circumference) |  | 3 years | 
| Mathematics examination result |  | 3 years | 
| Stage of pubertal development, self-assessed using the Tanner scale |  | 3 years | 
| Bone mineral content, lumbar spine and whole body minus head |  | 3 years | 
| Body composition including fat mass and fat-free soft tissue mass |  | 3 years | 
| Muscle strength (grip strength, elastic leg strength) |  | 3 years | 
| Estimated maximal oxygen uptake, derived from 20 meter shuttle test performance |  | 3 years | 
| Bronchial hyper-responsiveness to exercise |  | 3 years | 
| Sensitisation to aeroallergens |  | 3 years | 
| Concentrations of antigen-stimulated inflammatory mediators |  | 3 years | 
| Vitamin D status, parathyroid hormone and circulating markers of bone formation and modelling |  | 3 years | 
| Attention Deficit Hyperactivity Disorder Rating Scale-IV score |  | 3 years | 
| Cost-effectiveness of vitamin D3 for prevention of LTBI and active TB |  | 3 years | 
| Incidence of potential adverse reactions to vitamin D3 |  | 3 years | 
| Incidence of serious adverse events due to any cause |  | 3 years | 
| Incidence of fatal or life-threatening serious adverse events due to any cause |  | 3 years | 
| Proportion of participants sero-positive for SARS-CoV-2 at follow-up |  | 3 years | 
| Proportion of participants sero-positive for seasonal coronaviruses HKU1, 229E, OC43 and NL63 at follow-up |  | 3 years | 
| Proportion of participants sero-positive for influenza A and B at follow-up |  | 3 years |