Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids)

Keren Middelkoop¹, Justine Stewart¹, Neil Walker², Carmen Delport³, David A Jolliffe⁴, Anna K Coussens⁵, James Nuttall⁶, Jonathan C Y Tang⁷, William D Fraser⁷, Christopher J Griffiths², Geeta Trilok Kumar⁸, Suzanne Filteau⁹, Richard L Hooper², Robert J Wilkinson¹⁰, Linda-Gail Bekker³, Adrian R Martineau¹¹

Affiliations

¹ Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
² Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
³ Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, South Africa.
⁴ Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁵ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Infectious Diseases and Immune Defense Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
⁶ Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
⁷ Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK; Departments of Laboratory Medicine, Clinical Biochemistry, and Departments of Diabetes and Endocrinology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK.
⁸ Delhi School of Public Health, Institute of Eminence, University of Delhi, Delhi, India; Trivedi School of Biosciences, Ashoka University, Sonipat, India.
⁹ Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
¹⁰ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute, London, UK; Imperial College London, London, UK.
¹¹ Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address: a.martineau@qmul.ac.uk.

PMID: 37211272
DOI: 10.1016/j.ijid.2023.05.010

Free article

Clinical Trial

Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids)

Keren Middelkoop et al. Int J Infect Dis. 2023 Sep.

Free article

. 2023 Sep:134:63-70.

doi: 10.1016/j.ijid.2023.05.010. Epub 2023 May 20.

Authors

Affiliations

¹ Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, South Africa; Department of Medicine, University of Cape Town, Cape Town, South Africa.
² Wolfson Institute of Population Health, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
³ Desmond Tutu HIV Centre, Institute of Infectious Diseases & Molecular Medicine, University of Cape Town, Observatory, South Africa.
⁴ Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
⁵ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; Infectious Diseases and Immune Defense Division, Walter and Eliza Hall Institute of Medical Research, Parkville, Australia.
⁶ Paediatric Infectious Diseases Unit, Red Cross War Memorial Children's Hospital and the Department of Paediatrics and Child Health, University of Cape Town, Cape Town, South Africa.
⁷ Norwich Medical School, University of East Anglia, Norwich Research Park, Norwich, UK; Departments of Laboratory Medicine, Clinical Biochemistry, and Departments of Diabetes and Endocrinology, Norfolk and Norwich University Hospital NHS Foundation Trust, Norwich, UK.
⁸ Delhi School of Public Health, Institute of Eminence, University of Delhi, Delhi, India; Trivedi School of Biosciences, Ashoka University, Sonipat, India.
⁹ Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, UK.
¹⁰ Wellcome Centre for Infectious Diseases Research in Africa, Institute of Infectious Disease and Molecular Medicine, University of Cape Town, Cape Town, South Africa; The Francis Crick Institute, London, UK; Imperial College London, London, UK.
¹¹ Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. Electronic address: a.martineau@qmul.ac.uk.

PMID: 37211272
DOI: 10.1016/j.ijid.2023.05.010

Abstract

Objectives: To determine whether weekly oral supplementation with 10,000 IU vitamin D₃ for 3 years reduces the risk of sensitization to M. tuberculosis in South African schoolchildren aged 6-11 years with negative QuantiFERON-tuberculosis (TB) Gold Plus (QFT-Plus) assay results at baseline.

Methods: We conducted a phase 3 randomized placebo-controlled trial in 1682 children attending 23 primary schools in Cape Town. The primary outcome was a positive end-trial QFT-Plus result, analyzed using a mixed effects logistic regression model with the school of attendance included as a random effect.

Results: 829 vs. 853 QFT-Plus-negative children were randomized to receive vitamin D₃ vs. placebo, respectively. Mean end-study 25(OH)D concentrations in participants randomized to vitamin D vs. placebo were 104.3 vs 64.7 nmol/l, respectively (95% confidence interval for difference, 37.6 to 41.9 nmol/l). A total of 76/667 (11.4%) participants allocated to vitamin D vs. 89/687 (13.0%) participants allocated to placebo tested QFT-Plus positive at 3-year follow-up (adjusted odds ratio 0.86, 95% confidence interval 0.62-1.19, P = 0.35).

Conclusion: Weekly oral supplementation with 10,000 IU vitamin D₃ for 3 years elevated serum 25(OH)D concentrations among QFT-Plus-negative Cape Town schoolchildren but did not reduce their risk of QFT-Plus conversion.

Keywords: Interferon-gamma release assay; Randomized controlled trial; Tuberculosis; Vitamin D.

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Conflict of interest statement

Declarations of Competing Interest ARM declares receipt of funding in the last 36 months to support vitamin D research from the following companies who manufacture or sell vitamin D supplements: Pharma Nord Ltd, DSM Nutritional Products Ltd, Thornton & Ross Ltd and Hyphens Pharma Ltd. ARM also declares receipt of vitamin D capsules for clinical trial use from Pharma Nord Ltd, Synergy Biologics Ltd and Cytoplan Ltd; support for attending meetings from Pharma Nord Ltd and Abiogen Pharma Ltd; receipt of consultancy fees from DSM Nutritional Products Ltd and Qiagen Ltd; receipt of a speaker fee from the Linus Pauling Institute; participation on Data and Safety Monitoring Boards for the VITALITY trial (Vitamin D for Adolescents with HIV to reduce musculoskeletal morbidity and immunopathology, Pan African Clinical Trials Registry ref PACTR20200989766029) and the Trial of Vitamin D and Zinc Supplementation for Improving Treatment Outcomes Among COVID-19 Patients in India (ClinicalTrials.gov ref NCT04641195); and unpaid work as a Programme Committee member for the Vitamin D Workshop. All other authors declare that they have no competing interests.

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Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids)

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Vitamin D supplementation to prevent tuberculosis infection in South African schoolchildren: multicenter phase 3 double-blind randomized placebo-controlled trial (ViDiKids)

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Conflict of interest statement

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