Trial of Vitamin D Supplementation in Cape Town Primary Schoolchildren (ViDiKids)

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 Overview

• Status: Completed
• Conditions: Latent Tuberculosis
• Intervention / Treatment: Dietary supplement: Cholecalciferol; Other: Placebo

• Study Type: Interventional
• Enrollment (Actual): 1743
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Western Cape
    • Cape Town, Western Cape, South Africa, 7925
      • Desmond Tutu HIV Foundation

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 11 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intervention; Softgel capsule containing 10,000 IU (250 micrograms) cholecalciferol (vitamin D3) to be taken orally once per week for 3 years	Dietary supplement: Cholecalciferol; Weekly oral softgel capsule containing 10,000 IU (250 micrograms) cholecalciferol (vitamin D3); Other Names: Vitamin D3
Placebo Comparator: Placebo; 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; Weekly oral placebo softgel capsule

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Acquisition of latent tuberculosis infection	3 years

Secondary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Queen Mary University of London
• Collaborators: University of Cape Town
• Investigators: Principal Investigator: Keren Middelkoop, MPH, PhD, University of Cape Town

Study record dates

Study Major Dates

• Study Start (Actual): March 14, 2017
• Primary Completion (Actual): November 17, 2021
• Study Completion (Actual): June 30, 2022

Study Registration Dates

• First Submitted: July 18, 2016
• First Submitted That Met QC Criteria: August 22, 2016
• First Posted (Estimate): August 26, 2016

Study Record Updates

• Last Update Posted (Actual): September 8, 2022
• Last Update Submitted That Met QC Criteria: September 7, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Latent Infection; Tuberculosis; Latent Tuberculosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: 9408

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No