Latent TuberculosisPhase 3NCT02276755
Vitamin D Supplementation in TB Prevention
A Phase 3 study testing Cholecalciferol (vitamin D3) in people with Latent Tuberculosis, run by Harvard School of Public Health (HSPH) at 1 site in Mongolia.
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. Read more about this study
- Who is it for?
- Ages 6 to 13 yearsHealthy volunteers can take part
- Conditions the study is for
- Latent Tuberculosis
- What is being tested?
- Cholecalciferol (vitamin D3)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8,851 participants
- Where
- 1 siteMongolia
- Study dates
- Sep 2015to Jun 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 13 years
- All sexes
- Healthy volunteers accepted
- Child
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Vitamin D in TB Prevention in School Age Children
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
- Being tested
- Cholecalciferol (vitamin D3), Placebo
- Medical subject headings
- Latent Tuberculosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cholecalciferol (vitamin D3)Dietary supplement
14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA).
PlaceboOther
Placebo group will receive placebo (Tishcon, USA) weekly.
| Study group | Role | What they receive |
|---|---|---|
| Intervention: 1 | Active comparator | Dietary Supplement: Cholecalciferol (vitamin D3) Receives: Dietary Supplement: Cholecalciferol (vitamin D3) |
| Placebo Comparator: 2 | Placebo comparator | Dietary Supplement: Placebo Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Three years
Secondary outcomes (23)
Incidence of active TB disease
All participants
Measured: Three years
Incidence of self-reported acute respiratory infection (upper, lower and both combined)
All participants
Measured: Three years
Incidence of acute respiratory infection requiring hospitalization
All participants
Measured: Three years
Incidence of acute respiratory infections requiring antibiotic treatment
All participants
Measured: Three years
Number of days off school (total number and number due to acute respiratory infection)
All participants
Measured: Three years
Incidence of acute asthma exacerbation requiring hospitalization
Sub-set of participants with asthma at baseline
Measured: Three years
Incidence of new asthma, allergic rhinitis and atopic dermatitis
Sub-sets of participants without asthma, allergic rhinitis or atopic dermatitis at baseline
Measured: Three years
Control of asthma, allergic rhinitis and atopic dermatitis
Sub-sets of participants identified as having asthma, allergic rhinitis or atopic dermatitis at baseline
Measured: Three years
Incidence of bone fracture
All participants
Measured: Three years
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
Measured: Three years
Body composition: impedance, impedance%, fat mass fat %, and fat-free mass
All participants
Measured: Three years
Muscle strength: grip strength and long jump distance from standing
All participants
Measured: Three years
Serum 25-hydroxyvitamin D concentration
All participants
Measured: Three years
Bone mineral density at the radius
Sub-set of participants
Measured: Three years
Physical fitness (maximal oxygen consumption estimated from 20m shuttle run)
Sub-set of participants
Measured: Three years
Attention-related behavior scores (Connors III)
Sub-set of participants
Measured: Three years
Incidence of dental caries
Sub-set of participants
Measured: Three years
Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators
Sub-set of participants
Measured: Three years
Exam performance
Sub-set of participants
Measured: Three years
Self-reported pubertal development
Sub-set of participants
Measured: Three years
Spirometric lung volumes (FEV1 and FVC)
Sub-set of participants
Measured: Three years
Urinary metabolome profile
Sub-set of participants
Measured: Three years
Gut microbiome profile
Sub-set of participants
Measured: Three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Oct 2014 (estimated)
- Study startSep 2015
- Primary completionJun 2019
- Study completionJun 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Latent TuberculosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel assignment
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8,851 participants (actual)
Sponsor and investigators
- Lead sponsor
- Harvard School of Public Health (HSPH)
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ganmaa Davaasambuu, Harvard School of Public Health (HSPH)
- Investigators
- Davaasambuu Ganmaa, MD PhD, Principal investigator, Harvard School of Public Health (HSPH)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02276755
- Sponsor's protocol ID
- 140513
- Status last verified
- Jul 2020
- First submitted
- 23 Oct 2014
- Last updated
- 16 Jul 2020
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: 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.
Publications
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.
PubMed 39345833Ganmaa 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.
PubMed 38048799Ganmaa 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.
PubMed 36441522Ganmaa 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.
PubMed 32706534
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Vitamin D in TB Prevention in School Age Children
- ClinicalTrials.gov ID
- NCT02276755
- Acronym / sponsor ID
- 140513
- Conditions
- Latent Tuberculosis
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8,851 participants (actual)
- Lead sponsor
- Harvard School of Public Health (HSPH)University, hospital or other
- Study start
- Sep 2015 (actual)
- Primary completion
- Jun 2019 (actual)
- Study completion
- Jun 2020 (actual)
- First posted
- 28 Oct 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Parallel assignment
| Arm | Type | Receives |
|---|---|---|
| Intervention: 1 | Active comparator | Dietary Supplement: Cholecalciferol (vitamin D3)Dietary Supplement: Cholecalciferol (vitamin D3) |
| Placebo Comparator: 2 | Placebo comparator | Other: PlaceboDietary Supplement: Placebo |
Who may qualify
- Ages
- 6 to 13 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Cholecalciferol (vitamin D3)14000 IU vitamin D3 weekly Experimental group will receive vitamin D supplement (Tishcon, USA). | Dietary supplement | Intervention: 1 |
| PlaceboPlacebo group will receive placebo (Tishcon, USA) weekly. | Other | Placebo Comparator: 2 |
Primary outcome
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.
23 secondary outcomes
Incidence of active TB disease
Time frame: Three years
Incidence of self-reported acute respiratory infection (upper, lower and both combined)
Time frame: Three years
Incidence of acute respiratory infection requiring hospitalization
Time frame: Three years
Incidence of acute respiratory infections requiring antibiotic treatment
Time frame: Three years
Number of days off school (total number and number due to acute respiratory infection)
Time frame: Three years
Incidence of acute asthma exacerbation requiring hospitalization
Time frame: Three years
Incidence of new asthma, allergic rhinitis and atopic dermatitis
Time frame: Three years
Control of asthma, allergic rhinitis and atopic dermatitis
Time frame: Three years
Incidence of bone fracture
Time frame: Three years
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
Body composition: impedance, impedance%, fat mass fat %, and fat-free mass
Time frame: Three years
Muscle strength: grip strength and long jump distance from standing
Time frame: Three years
Serum 25-hydroxyvitamin D concentration
Time frame: Three years
Bone mineral density at the radius
Time frame: Three years
Physical fitness (maximal oxygen consumption estimated from 20m shuttle run)
Time frame: Three years
Attention-related behavior scores (Connors III)
Time frame: Three years
Incidence of dental caries
Time frame: Three years
Circulating and antigen-stimulated concentrations of cytokines, chemokines and other inflammatory mediators
Time frame: Three years
Exam performance
Time frame: Three years
Self-reported pubertal development
Time frame: Three years
Spirometric lung volumes (FEV1 and FVC)
Time frame: Three years
Urinary metabolome profile
Time frame: Three years
Gut microbiome profile
Time frame: Three years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2020.
- Derived from this study: PubMed 39345833Ganmaa 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.
- Derived from this study: PubMed 38048799Ganmaa 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.
- Derived from this study: PubMed 36441522Ganmaa 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.
- Derived from this study: PubMed 32706534Ganmaa 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.
- Individual participant dataSharing planned: Yes. 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Davaasambuu Ganmaa, MD PhD principal investigator
Harvard School of Public Health (HSPH)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cholecalciferol (vitamin D3) in people with Latent Tuberculosis, run by Harvard School of Public Health (HSPH) at 1 site in Mongolia.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Mongolia. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Acquisition of latent tuberculosis infection (time frame: Three years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02276755, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Jul 2020.