ICTBSG: Micronutrient Supplementation in in Paediatric Pulmonary Tuberculosis

Sponsor

All India Institute of Medical Sciences, New Delhi (Other)

Overall Status

Completed

CT.gov ID

NCT00801606

Collaborator

University of Bergen (Other)

403

Enrollment

Location

Arms

Duration (Months)

9.6

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Tuberculosis	Drug: Zinc Drug: Micronutrient without zinc Drug: Micronutrient with zinc Drug: Placebo	Phase 3

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:

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

403 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Dec 1, 2008

Actual Primary Completion Date :

Jun 1, 2012

Actual Study Completion Date :

Jun 1, 2012

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Change in Z score for weight and improvement in X ray film [6 months]

Secondary Outcome Measures

Resolution of symptoms and interferon gamma activity at 2 and 6 months [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

6 Months to 15 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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