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Vitamin D Supplementation in TB Prevention

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ClinicalTrials.gov Identifier: NCT02276755
Recruitment Status : Active, not recruiting
First Posted : October 28, 2014
Last Update Posted : May 29, 2019
Sponsor:
Information provided by (Responsible Party):
Ganmaa Davaasambuu, Harvard School of Public Health

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.

Condition or disease Intervention/treatment Phase
Latent Tuberculosis Dietary Supplement: Cholecalciferol (vitamin D3) Other: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 8851 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Parallel assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Vitamin D in TB Prevention in School Age Children
Actual Study Start Date : September 2015
Estimated Primary Completion Date : June 2019
Estimated Study Completion Date : June 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Intervention: 1
Dietary Supplement: Cholecalciferol (vitamin D3)
Dietary Supplement: Cholecalciferol (vitamin D3)
14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA).

Placebo Comparator: Placebo Comparator: 2
Dietary Supplement: Placebo
Other: Placebo
Placebo group will receive placebo (Tishcon, USA) weekly.




Primary Outcome Measures :
  1. Acquisition of latent tuberculosis infection [ Time Frame: Three years ]
    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.


Secondary Outcome Measures :
  1. Incidence of active TB disease [ Time Frame: Three years ]
    All participants

  2. Incidence of self-reported acute respiratory infection (upper, lower and both combined) [ Time Frame: Three years ]
    All participants

  3. Incidence of acute respiratory infection requiring hospitalization [ Time Frame: Three years ]
    All participants

  4. Incidence of acute respiratory infections requiring antibiotic treatment [ Time Frame: Three years ]
    All participants

  5. Number of days off school (total number and number due to acute respiratory infection) [ Time Frame: Three years ]
    All participants

  6. Incidence of acute asthma exacerbation requiring hospitalization [ Time Frame: Three years ]
    Sub-set of participants with asthma at baseline

  7. Incidence of new asthma, allergic rhinitis and atopic dermatitis [ Time Frame: Three years ]
    Sub-sets of participants without asthma, allergic rhinitis or atopic dermatitis at baseline

  8. Control of asthma, allergic rhinitis and atopic dermatitis [ Time Frame: Three years ]
    Sub-sets of participants identified as having asthma, allergic rhinitis or atopic dermatitis at baseline

  9. Incidence of bone fracture [ Time Frame: Three years ]
    All participants

  10. 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) [ Time Frame: Three years ]
    All participants

  11. Body composition: impedance, impedance%, fat mass fat %, and fat-free mass [ Time Frame: Three years ]
    All participants

  12. Muscle strength: grip strength and long jump distance from standing [ Time Frame: Three years ]
    All participants

  13. Serum 25-hydroxyvitamin D concentration [ Time Frame: Three years ]
    All participants

  14. Bone mineral density at the radius [ Time Frame: Three years ]
    Sub-set of participants

  15. Physical fitness (maximal oxygen consumption estimated from 20m shuttle run) [ Time Frame: Three years ]
    Sub-set of participants

  16. Attention-related behavior scores (Connors III) [ Time Frame: Three years ]
    Sub-set of participants

  17. Incidence of dental caries [ Time Frame: Three years ]
    Sub-set of participants

  18. Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators [ Time Frame: Three years ]
    Sub-set of participants

  19. Exam performance [ Time Frame: Three years ]
    Sub-set of participants

  20. Self-reported pubertal development [ Time Frame: Three years ]
    Sub-set of participants

  21. Spirometric lung volumes (FEV1 and FVC) [ Time Frame: Three years ]
    Sub-set of participants

  22. Urinary metabolome profile [ Time Frame: Three years ]
    Sub-set of participants

  23. Gut microbiome profile [ Time Frame: Three years ]
    Sub-set of participants


Other Outcome Measures:
  1. Incidence of adverse events [ Time Frame: Three years ]
    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.

  2. Heterogeneity of treatment effect among sub-groups defined by baseline vitamin D status, estimated calcium intake and vitamin D pathway genotype [ Time Frame: Three years ]

    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:

    1. An interaction term between baseline vitamin D status and allocation to vitamin D vs. placebo
    2. An interaction term between estimated calcium intake and allocation to vitamin D vs. placebo
    3. 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).


  3. Cost-effectiveness of vitamin D supplementation for the prevention of LTBI and active TB [ Time Frame: Three years ]
    Health economic analysis



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Ages Eligible for Study:   6 Years to 13 Years   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02276755


Locations
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Mongolia
Mongolian Health Initiative
Ulaanbaatar, Mongolia
Sponsors and Collaborators
Harvard School of Public Health
Investigators
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Principal Investigator: Davaasambuu Ganmaa, MD PhD Harvard School of Public Health
  Study Documents (Full-Text)

Documents provided by Ganmaa Davaasambuu, Harvard School of Public Health:

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Responsible Party: Ganmaa Davaasambuu, Assistant Professor, Harvard School of Public Health
ClinicalTrials.gov Identifier: NCT02276755     History of Changes
Other Study ID Numbers: 140513
First Posted: October 28, 2014    Key Record Dates
Last Update Posted: May 29, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD will be shared for purposes of meta-analysis, subject to approval from IRBs in Mongolia and the USA and terms of data sharing agreements.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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
Additional relevant MeSH terms:
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Tuberculosis
Latent Tuberculosis
Mycobacterium Infections
Actinomycetales Infections
Gram-Positive Bacterial Infections
Bacterial Infections
Vitamin D
Ergocalciferols
Cholecalciferol
Vitamins
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents
Calcium-Regulating Hormones and Agents