Vitamin D Supplementation in TB Prevention

NCT02276755 | Completed Phase 3 DMC

• 1 other identifier: 140513
• Study Type: interventional
• Target: 8,851
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to determine whether vitamin D supplementation reduces risk of acquiring latent tuberculosis infection (LTBI) in school age children in Mongolia. The investigators hypothesize that (1) vitamin D supplementation will reduce risk of acquisition of LTBI, (2) vitamin D supplementation will safely reduce risk of developing active TB and improve other secondary efficacy outcomes, and (3) children with the lowest vitamin D status at baseline will gain most from the intervention.

Conditions

Latent Tuberculosis

Outcome Measures

Primary Outcomes (1)

• Acquisition of latent tuberculosis infection

  The proportion of children who acquire LTBI during the 3 year period will be compared for children randomized to vitamin D3 vs. placebo using the Mantel-Haenszel risk ratio, stratified by school of attendance. The primary analysis will compare the proportion of children who are QuantiFERON-positive at the 0.35 IU/ml IFN-gamma threshold at the end of the study. Exploratory analyses will compare the proportion of children who are positive at the 4.0 IU/ml IFN-gamma threshold (denoting stable conversion) and mean / median antigen-stimulated IFN-gamma concentration analyzed as a continuous variable.

  Three years

Secondary Outcomes (23)

• Incidence of active TB disease

  Three years

• Incidence of self-reported acute respiratory infection (upper, lower and both combined)

  Three years

• Incidence of acute respiratory infection requiring hospitalization

  Three years

• Incidence of acute respiratory infections requiring antibiotic treatment

  Three years

• Number of days off school (total number and number due to acute respiratory infection)

  Three years

Other Outcomes (3)

• Incidence of adverse events

  Three years

• Heterogeneity of treatment effect among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype

  Three years

• Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB

  Three years

Study Arms (2)

Intervention: 1

ACTIVE COMPARATOR

Dietary Supplement: Cholecalciferol (vitamin D3)

Dietary Supplement: Cholecalciferol (vitamin D3)

Placebo Comparator: 2

PLACEBO COMPARATOR

Dietary Supplement: Placebo

Other: Placebo

Interventions

Cholecalciferol (vitamin D3) DIETARY_SUPPLEMENT

14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA).

Intervention: 1

Placebo OTHER

Placebo group will receive placebo (Tishcon, USA) weekly.

Placebo Comparator: 2

Eligibility Criteria

• Age: 6 Years - 13 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Boys or girls aged 6 to 13 years at enrolment
• Attending participating school in Ulaanbaatar at enrolment
• Child gives informed assent to participate in the study
• Child's parent/legal guardian gives informed consent for child to participate in study

You may not qualify if:

• Chronic medical conditions
• Presence of LTBI on screening, as evidenced by a positive QFT-G
• Clinical signs of rickets, or diagnosis of any other condition requiring vitamin D supplementation
• Known primary hyperparathyroidism or sarcoidosis
• Taking immunosuppressant or cytotoxic therapy, or vitamin D supplement \> 400IU / day
• Plans to move away from study area within 3 years of enrolment

Sponsors & Collaborators

• Harvard School of Public Health (HSPH): lead

Study Sites (1)

Mongolian Health Initiative

Ulaanbaatar, Mongolia

Location

Related Publications (4)

• Ganmaa D, Hemmings S, Jolliffe DA, Buyanjargal U, Garmaa G, Adiya U, Tumurbaatar T, Dorjnamjil K, Tserenkhuu E, Erdenenbaatar S, Tsendjav E, Enkhamgalan N, Achtai CE, Talhaasuren Y, Byambasuren T, Ganbaatar E, Purevdorj E, Martineau AR. Influence of vitamin D supplementation on muscle strength and exercise capacity in Mongolian schoolchildren: secondary outcomes from a randomised controlled trial. BMJ Open Sport Exerc Med. 2024 Sep 26;10(3):e002018. doi: 10.1136/bmjsem-2024-002018. eCollection 2024.

  PMID: 39345833 DERIVED

• Ganmaa D, Khudyakov P, Buyanjargal U, Tserenkhuu E, Erdenenbaatar S, Achtai CE, Yansanjav N, Delgererekh B, Ankhbat M, Tsendjav E, Ochirbat B, Jargalsaikhan B, Enkhmaa D, Martineau AR. Vitamin D supplements for fracture prevention in schoolchildren in Mongolia: analysis of secondary outcomes from a multicentre, double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2024 Jan;12(1):29-38. doi: 10.1016/S2213-8587(23)00317-0. Epub 2023 Dec 1.

  PMID: 38048799 DERIVED

• Ganmaa D, Bromage S, Khudyakov P, Erdenenbaatar S, Delgererekh B, Martineau AR. Influence of Vitamin D Supplementation on Growth, Body Composition, and Pubertal Development Among School-aged Children in an Area With a High Prevalence of Vitamin D Deficiency: A Randomized Clinical Trial. JAMA Pediatr. 2023 Jan 1;177(1):32-41. doi: 10.1001/jamapediatrics.2022.4581.

  PMID: 36441522 DERIVED

• Ganmaa D, Uyanga B, Zhou X, Gantsetseg G, Delgerekh B, Enkhmaa D, Khulan D, Ariunzaya S, Sumiya E, Bolortuya B, Yanjmaa J, Enkhtsetseg T, Munkhzaya A, Tunsag M, Khudyakov P, Seddon JA, Marais BJ, Batbayar O, Erdenetuya G, Amarsaikhan B, Spiegelman D, Tsolmon J, Martineau AR. Vitamin D Supplements for Prevention of Tuberculosis Infection and Disease. N Engl J Med. 2020 Jul 23;383(4):359-368. doi: 10.1056/NEJMoa1915176.

  PMID: 32706534 DERIVED

MeSH Terms

Conditions

Latent Tuberculosis

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Tuberculosis; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Latent Infection

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Study Officials

• Davaasambuu Ganmaa, MD PhD

  Harvard School of Public Health (HSPH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Model Details: Parallel assignment

Study Record Dates

• First Submitted: October 23, 2014
• First Posted: October 28, 2014
• Study Start: September 1, 2015
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2020
• Last Updated: July 16, 2020

Record last verified: 2020-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The items above will be shared following publication of trial reports.
• Access Criteria: IPD requests should be made to the Principal Investigator: gdavaasa@hsph.harvard.edu

Locations

MO (1)