Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren

Queen Mary University of London1,743 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

1,743

Conditions

Latent Tuberculosis

Interventions

Eligibility

Sex: ALLMin age: 6 YearsMax age: 11 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Acquisition of latent tuberculosis infection

Time frame: 3 years

Secondary Outcomes

Incidence of active tuberculosis (TB)

Time frame: 3 years

Incidence of acute respiratory infection

Time frame: 3 years

Incidence of acute asthma exacerbation

Time frame: 3 years

Incidence and control of asthma, allergic rhinitis and atopic dermatitis

Time frame: 3 years

Incidence of bone fracture

Time frame: 3 years

Anthropometric outcomes (weight, height, body mass index, waist circumference)

Time frame: 3 years

Mathematics examination result

Time frame: 3 years

Stage of pubertal development, self-assessed using the Tanner scale

Time frame: 3 years

Bone mineral content, lumbar spine and whole body minus head

Time frame: 3 years

Body composition including fat mass and fat-free soft tissue mass

Time frame: 3 years

Muscle strength (grip strength, elastic leg strength)

Time frame: 3 years

Estimated maximal oxygen uptake, derived from 20 meter shuttle test performance

Time frame: 3 years

Bronchial hyper-responsiveness to exercise

Time frame: 3 years

Sensitisation to aeroallergens

Time frame: 3 years

Concentrations of antigen-stimulated inflammatory mediators

Time frame: 3 years

Vitamin D status, parathyroid hormone and circulating markers of bone formation and modelling

Time frame: 3 years

Attention Deficit Hyperactivity Disorder Rating Scale-IV score

Time frame: 3 years

Cost-effectiveness of vitamin D3 for prevention of LTBI and active TB

Time frame: 3 years

Incidence of potential adverse reactions to vitamin D3

Time frame: 3 years

Incidence of serious adverse events due to any cause

Time frame: 3 years

Incidence of fatal or life-threatening serious adverse events due to any cause

Time frame: 3 years

Proportion of participants sero-positive for SARS-CoV-2 at follow-up

Time frame: 3 years

Proportion of participants sero-positive for seasonal coronaviruses HKU1, 229E, OC43 and NL63 at follow-up

Time frame: 3 years

Proportion of participants sero-positive for influenza A and B at follow-up

Time frame: 3 years

Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes