Latent Tuberculosis
Conditions
Brief summary
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.
Interventions
DIETARY_SUPPLEMENTCholecalciferol
Weekly oral softgel capsule containing 10,000 IU (250 micrograms) cholecalciferol (vitamin D3)
OTHERPlacebo
Weekly oral placebo softgel capsule
Sponsors
University of Cape Town
Queen Mary University of London
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
6 Years to 11 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Acquisition of latent tuberculosis infection | 3 years |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Incidence of active tuberculosis (TB) | 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 |
| Bronchial hyper-responsiveness to exercise | 3 years |
Countries
South Africa
Outcome results
None listed