Micronutrient Supplementation in in Paediatric Pulmonary Tuberculosis (ICTBSG)

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

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.

Study Overview

• Status: Completed
• Conditions: Tuberculosis
• Intervention / Treatment: Drug: Placebo; Drug: Zinc; Drug: Micronutrient without zinc; Drug: Micronutrient with zinc

Detailed Description

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:

1. Effect of micronutrient supplements at 2 and 6 months on anthropometric parameters by comparing means of anthropometric parameters in different groups.
2. 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.
3. 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
4. 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.
5. Interferon gamma responses to M. tuberculosis antigens ESAT6 and CF10 by quantiferon assay at baseline, 2 months and 6 months of treatment
6. To study effect of zinc supplementation on ocular toxicity in children receiving ethambutol by VER
7. To document drug resistance (S, I, R, E) patterns among children with culture confirmed TB
8. To document genotypic strain diversity among children with culture confirmed TB, also associations between strain type and disease severity and/or drug resistance
9. To document the spectrum of mycobacterial species by culture in children clinically suspected of having pulmonary tuberculosis.

• Study Type: Interventional
• Enrollment (Actual): 403
• Phase: Phase 3

Contacts and Locations

Study Locations

• India
  • Delhi
    • New Delhi, Delhi, India, 110029
      • Department of Pediatrics, All India Institute of Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Study drug containing zinc alone; Zinc 20 mg daily	Drug: Zinc; Zinc 20 mg/day; Other Names: study drug
Experimental: Study drug Micronutrient without zinc; 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; Multimineral 2 RDA; Other Names: study drug
Experimental: Study drug Micronutrient with zinc; 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; Multimineral 2 RDA and zinc 20 mg per day; Other Names: study drug
Placebo Comparator: Placebo; Placebo only	Drug: Placebo; Placebo; Other Names: study drug

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: All India Institute of Medical Sciences, New Delhi
• Collaborators: University of Bergen
• Investigators: Principal Investigator: Sushil Kr Kabra, MD, All India Institute of Medical Sciences, New Delhi

Publications and helpful links

General Publications

• Lodha R, Mukherjee A, Singh V, Singh S, Friis H, Faurholt-Jepsen D, Bhatnagar S, Saini S, Kabra SK, Grewal HM; Delhi Pediatric TB Study Group. Effect of micronutrient supplementation on treatment outcomes in children with intrathoracic tuberculosis: a randomized controlled trial. Am J Clin Nutr. 2014 Nov;100(5):1287-97. doi: 10.3945/ajcn.113.082255. Epub 2014 Sep 10.

Study record dates

Study Major Dates

• Study Start: December 1, 2008
• Primary Completion (Actual): June 1, 2012
• Study Completion (Actual): June 1, 2012

Study Registration Dates

• First Submitted: December 2, 2008
• First Submitted That Met QC Criteria: December 2, 2008
• First Posted (Estimate): December 3, 2008

Study Record Updates

• Last Update Posted (Estimate): February 10, 2016
• Last Update Submitted That Met QC Criteria: February 8, 2016
• Last Verified: February 1, 2016

More Information

Terms related to this study

• Keywords: Micronutrient; Childhood Tuberculosis
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Actinomycetales Infections; Mycobacterium Infections; Tuberculosis; Tuberculosis, Pulmonary; Physiological Effects of Drugs; Micronutrients; Trace Elements; Zinc
• Other Study ID Numbers: ICTBSG

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No