Micronutrient Supplementation in in Paediatric Pulmonary Tuberculosis

Study Overview
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Brief Summary
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A recent trial in adults has demonstrated that zinc (Zn) and other Multiminerals (MN) combined, but neither of them alone, significantly increased weight gain during Tuberculosis (TB) treatment. There was a substantially larger beneficial effect on survival amongst those who received the combination of Zn and MN compared with those who received either Zn alone or MN alone. These exciting preliminary findings require further confirmation, as the data on mortality reduction was based on a post-hoc subgroup-analysis. Effects of MN and Zn supplementation has not been assessed in children with TB. Studies are urgently needed to evaluate the therapeutic potential of nutritional interventions on treatment outcome in children with TB. Simple and inexpensive nutritional interventions may substantially impact TB-related child morbidity and mortality in high-burden settings. The investigators thus, propose a randomized, double blind, controlled trial that will measure the effect of multi-vitamin/mineral supplementation on the efficacy of anti-TB treatment in newly diagnosed childhood pulmonary TB patients in Delhi.

Detailed Description
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We plan to do a randomized controlled trial to study impact of multimineral supplement with antituberculosis drugs in freshly diagnosed pulmonary tuberculosis in children. Plan to enrol 400 children at two sites in Delhi. The diagnosis and treatment of pulmonary tuberculosis will be based on recommendations of Revised National Tuberculosis Control Program (RNTCP). The outcome will be measured in form of weight gain and improvement in x ray film of chest. The secondary outcome variables will be as follows: Effect of micronutrient supplements at 2 and 6 months on anthropometric parameters by comparing means of anthropometric parameters in different groups. Improvement in radiological findings at 2 months: Comparing the proportion of children showing clearance of X ray films at baseline and 6 months by two paediatricians independently using same protocol. Resolution of symptoms at 2 and 6 months: By comparing proportion of patients having resolution of presenting symptoms (fever, cough, appetite improvement) as reported by parents Proportion of children requiring extension of intensive phase of therapy: Comparing proportion of children in different groups requiring extension of intensive phase of therapy at 2 months due to the treating physician's decision. Interferon gamma responses to M. tuberculosis antigens ESAT6 and CF10 by quantiferon assay at baseline, 2 months and 6 months of treatment To study effect of zinc supplementation on ocular toxicity in children receiving ethambutol by VER To document drug resistance (S, I, R, E) patterns among children with culture confirmed TB To document genotypic strain diversity among children with culture confirmed TB, also associations between strain type and disease severity and/or drug resistance To document the spectrum of mycobacterial species by culture in children clinically suspected of having pulmonary tuberculosis.

Official Title
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Micronutrient Supplementation in Conjunction With Standard Anti-Tuberculosis Therapy in Paediatric (6 Months-15 Years) New Pulmonary Tuberculosis Patients

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: Zinc
* Drug: Micronutrient without zinc
* Drug: Micronutrient with zinc
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: New pulmonary (including pleural) tuberculosis with/without an extrapulmonary lesion in children age 6 months to 15 years Exclusion Criteria: Weight for height < 70 % of NCHS median (reason: zinc as per guidelines is given as standard point of care to all severely malnourished children) Bilateral pedal oedema Known HIV + ve Place of residence outside Delhi (including physicians discretion) History of previous ATT treatment or INH prophylaxis for more than 48 hours prior to enrollment Signs of upper airway obstruction, or an arterial oxygen saturation less than 92% in room air Signs of renal, hepatic, or cvs disease Unable to attend follow up session for reading of Mantoux tests Documented intake of zinc continuously for > 2 weeks in the preceding 4 weeks at enrollment CNS, osteo-articular, pericardial, renal TB History of contact with a documented case of drug resistant TB

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 15 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study drug containing zinc alone<br>Zinc 20 mg daily | Drug: Zinc<br>* Zinc 20 mg/day<br>* Other names: study drug;|
| Experimental: Study drug Micronutrient without zinc<br>micronutrients (vitamin A, thiamine, riboflavin, vitamins B-6 and B-12, folic acid, niacin, vitamins C, E, and D, selenium, and copper) without zinc. | Drug: Micronutrient without zinc<br>* Multimineral 2 RDA<br>* Other names: study drug;|
| Experimental: Study drug Micronutrient with zinc<br>micronutrients in combination with zinc (vitamin A, thiamine, riboflavin, vitamin B-6 and B-12, folic acid, niacin, vitamins C, E, and D, selenium, copper, and 20 mg elemental zinc). | Drug: Micronutrient with zinc<br>* Multimineral 2 RDA and zinc 20 mg per day<br>* Other names: study drug;|
| Placebo Comparator: Placebo<br>Placebo only | Drug: Placebo<br>* Placebo<br>* Other names: study drug;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Z score for weight and improvement in X ray film |  | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Resolution of symptoms and interferon gamma activity at 2 and 6 months |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Micronutrient, Childhood Tuberculosis