Vitamin D Supplementation in TB Prevention

Latent Tuberculosis Clinical Trial

Official title:

Vitamin D in TB Prevention in School Age Children

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02276755
• Other study ID #: 140513
• Status: Completed
• Phase: Phase 3
• Start date: September 2015
• Est. completion date: June 2020

Study information

• Verified date: July 2020
• Source: Harvard School of Public Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 8851
• Est. completion date: June 2020
• Est. primary completion date: June 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 6 Years to 13 Years

Eligibility

Inclusion Criteria:

1. Boys or girls aged 6 to 13 years at enrolment

2. Attending participating school in Ulaanbaatar at enrolment

3. Child gives informed assent to participate in the study

4. Child's parent/legal guardian gives informed consent for child to participate in study

Exclusion Criteria:

1. Chronic medical conditions

2. Presence of LTBI on screening, as evidenced by a positive QFT-G

3. Clinical signs of rickets, or diagnosis of any other condition requiring vitamin D supplementation

4. Known primary hyperparathyroidism or sarcoidosis

5. Taking immunosuppressant or cytotoxic therapy, or vitamin D supplement > 400IU / day

6. Plans to move away from study area within 3 years of enrolment

Related Conditions & MeSH terms

• Latent Tuberculosis
• Tuberculosis

Intervention

Dietary Supplement:
• Cholecalciferol (vitamin D3)
14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA).

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

Locations

Country	Name	City	State
Mongolia	Mongolian Health Initiative	Ulaanbaatar

Sponsors (1)

Lead Sponsor	Collaborator
Harvard School of Public Health

Country where clinical trial is conducted

Mongolia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Incidence of adverse events	The proportion of participants experiencing death, one or more serious adverse events of any cause or one or more potential adverse reactions (hypercalcemia, hypercalciuria and hypervitaminosis D) will be compared between arms.	Three years
Other	Heterogeneity of treatment effect among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype	Heterogeneity of treatment effect will be examined among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype for primary and secondary outcomes. This will be done by repeating efficacy analyses to include: An interaction term between baseline vitamin D status and allocation to vitamin D vs. placebo; An interaction term between estimated calcium intake and allocation to vitamin D vs. placebo; An interaction term between vitamin D pathway genotype and allocation to vitamin D vs. placebo.; For genetic analyses, DNA will be extracted from participants' stored whole blood, and typed for a panel of candidate single nucleotide polymorphisms (SNPs) in genes influencing vitamin D metabolism (e.g. CYP2R1, CYP27B1, CYP24A1), transport (e.g. DBP) and signalling (e.g. VDR).	Three years
Other	Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB	Health economic analysis	Three years
Primary	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	Incidence of active TB disease	All participants	Three years
Secondary	Incidence of self-reported acute respiratory infection (upper, lower and both combined)	All participants	Three years
Secondary	Incidence of acute respiratory infection requiring hospitalization	All participants	Three years
Secondary	Incidence of acute respiratory infections requiring antibiotic treatment	All participants	Three years
Secondary	Number of days off school (total number and number due to acute respiratory infection)	All participants	Three years
Secondary	Incidence of acute asthma exacerbation requiring hospitalization	Sub-set of participants with asthma at baseline	Three years
Secondary	Incidence of new asthma, allergic rhinitis and atopic dermatitis	Sub-sets of participants without asthma, allergic rhinitis or atopic dermatitis at baseline	Three years
Secondary	Control of asthma, allergic rhinitis and atopic dermatitis	Sub-sets of participants identified as having asthma, allergic rhinitis or atopic dermatitis at baseline	Three years
Secondary	Incidence of bone fracture	All participants	Three years
Secondary	Anthropometric outcomes (z-scores for height-for-age, weight-for-age, weight-for-height, body mass index-for-age, and waist circumference and waist-to-height ratio)	All participants	Three years
Secondary	Body composition: impedance, impedance%, fat mass fat %, and fat-free mass	All participants	Three years
Secondary	Muscle strength: grip strength and long jump distance from standing	All participants	Three years
Secondary	Serum 25-hydroxyvitamin D concentration	All participants	Three years
Secondary	Bone mineral density at the radius	Sub-set of participants	Three years
Secondary	Physical fitness (maximal oxygen consumption estimated from 20m shuttle run)	Sub-set of participants	Three years
Secondary	Attention-related behavior scores (Connors III)	Sub-set of participants	Three years
Secondary	Incidence of dental caries	Sub-set of participants	Three years
Secondary	Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators	Sub-set of participants	Three years
Secondary	Exam performance	Sub-set of participants	Three years
Secondary	Self-reported pubertal development	Sub-set of participants	Three years
Secondary	Spirometric lung volumes (FEV1 and FVC)	Sub-set of participants	Three years
Secondary	Urinary metabolome profile	Sub-set of participants	Three years
Secondary	Gut microbiome profile	Sub-set of participants	Three years