Clinical trial NCT02880982: Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren
Official title: Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Latent Tuberculosis
Lead sponsor: Queen Mary University of London
Sponsor class: OTHER
Collaborators: name: University of Cape Town
First posted: 2016-08-26
Enrollment: 1743
Sex: ALL
Minimum age (years): 6
Maximum age (years): 11
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility criteria: 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

Primary outcomes:
measure: Acquisition of latent tuberculosis infection
timeFrame: 3 years
Secondary outcomes:
measure: Incidence of active tuberculosis (TB)
timeFrame: 3 years
measure: Incidence of acute respiratory infection
timeFrame: 3 years
measure: Incidence of acute asthma exacerbation
timeFrame: 3 years
measure: Incidence and control of asthma, allergic rhinitis and atopic dermatitis
timeFrame: 3 years
measure: Incidence of bone fracture
timeFrame: 3 years
measure: Anthropometric outcomes (weight, height, body mass index, waist circumference)
timeFrame: 3 years
measure: Mathematics examination result
timeFrame: 3 years
measure: Stage of pubertal development, self-assessed using the Tanner scale
timeFrame: 3 years
measure: Bone mineral content, lumbar spine and whole body minus head
timeFrame: 3 years
measure: Body composition including fat mass and fat-free soft tissue mass
timeFrame: 3 years
measure: Muscle strength (grip strength, elastic leg strength)
timeFrame: 3 years
measure: Estimated maximal oxygen uptake, derived from 20 meter shuttle test performance
timeFrame: 3 years
measure: Bronchial hyper-responsiveness to exercise
timeFrame: 3 years
measure: Sensitisation to aeroallergens
timeFrame: 3 years
measure: Concentrations of antigen-stimulated inflammatory mediators
timeFrame: 3 years
measure: Vitamin D status, parathyroid hormone and circulating markers of bone formation and modelling
timeFrame: 3 years
measure: Attention Deficit Hyperactivity Disorder Rating Scale-IV score
timeFrame: 3 years
measure: Cost-effectiveness of vitamin D3 for prevention of LTBI and active TB
timeFrame: 3 years
measure: Incidence of potential adverse reactions to vitamin D3
timeFrame: 3 years
measure: Incidence of serious adverse events due to any cause
timeFrame: 3 years
measure: Incidence of fatal or life-threatening serious adverse events due to any cause
timeFrame: 3 years
measure: Proportion of participants sero-positive for SARS-CoV-2 at follow-up
timeFrame: 3 years
measure: Proportion of participants sero-positive for seasonal coronaviruses HKU1, 229E, OC43 and NL63 at follow-up
timeFrame: 3 years
measure: Proportion of participants sero-positive for influenza A and B at follow-up
timeFrame: 3 years
Other outcomes:
Locations:
city: Cape Town
country: South Africa
facility: Desmond Tutu HIV Foundation
state: Western Cape
Study officials:
affiliation: University of Cape Town
name: Keren Middelkoop, MPH, PhD
role: PRINCIPAL_INVESTIGATOR
References: