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Folic Acid and Vitamin B12 in Young Indian Children

Phase 2
Completed
Conditions
Diarrhea
Pneumonia
Interventions
Dietary Supplement: Placebo
Dietary Supplement: Folic acid and vitamin B12
Dietary Supplement: Folic Acid
Dietary Supplement: Vitamin B12
Registration Number
NCT00717730
Lead Sponsor
Tor A. Strand
Brief Summary

Hypothesis: Supplementation of two recommended daily allowances (RDA) of folic acid with or without simultaneous administration of vitamin B12 reduces the rates of acute lower respiratory tract infections (ALRI), clinical pneumonia and diarrhea.

Design/Methods We will conduct a preventive randomized placebo controlled clinical trial of folic acid and vitamin B12 supplementation in 1000 children aged 6 to 30 months living in a low to middle-income socioeconomic setting in New Delhi, India. Children aged 6-30 months will be identified through a survey. Eligible and willing Children aged 6-30 months will be randomized to 4 treatment groups. Trial to enrollment informed consent will be obtained by the Study Physician/Supervisor. At enrollment a baseline form will be filled and the child weight and length taken. The baseline blood samples will be collected. The supplements will be given daily for 6 months. Morbidity will be ascertained through biweekly home visits by field workers.

Detailed Description

Pneumonia and diarrhea are among the leading causes of poor health and death in young children of developing countries.

Many of these children have inadequate intakes of several vitamins and minerals. Folate and vitamin B12 are important for normal function of the immune system. Deficiencies of these vitamins are often part of general malnutrition and might be responsible for the excess morbidity and mortality seen in malnourished children. In a recent cohort study in almost 2,500 Indian children we demonstrated that those with poor folate status had higher rates of diarrhea and pneumonia. This study also showed that children that were not breastfed had poor folate status and our analyses suggested that the effect of breastfeeding in preventing respiratory and gastrointestinal infections could be explained by the folate content of breast milk. The finding that poor folate status is related to increased susceptibility to childhood infections needs to be confirmed in well conducted clinical trials in populations where folate deficiency is prevalent.

This trial aims to examine whether daily supplementation of 2 recommended doses of folate or vitamin B12 or both will lessen the incidence of acute lower respiratory tract infections and diarrhea. We will also measure if the supplementation improves the weight and length of supplemented children.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1000
Inclusion Criteria
  • Age: 6 to 30 months
  • Either sex
  • Likely to reside in area for next 6 months
Exclusion Criteria
  • Severe systemic illness requiring hospitalization
  • Severe malnutrition, i.e. weight for height < -3 z of the WHO standard for this age group. For ethical reasons these children require micronutrient supplementation and adequate medical care.
  • Non consent
  • Consuming vitamin supplements that include folic acid and vitamin B12.
  • Severe anemia (Hb < 7 g/dL).

Study & Design

Study Type
INTERVENTIONAL
Study Design
FACTORIAL
Arm && Interventions
GroupInterventionDescription
APlaceboPlacebo dietary supplement
DFolic acid and vitamin B12Folic acid and Vitamin B12
BFolic AcidFolic acid
CVitamin B12Vitamin B12
Primary Outcome Measures
NameTimeMethod
Number of episodes diarrhea (all, severe, prolonged) and pneumonia (ALRI, Clinical pneumonia)6 months
Prevalence of diarrhea6 months
Secondary Outcome Measures
NameTimeMethod
Adverse events (vomiting and gastric discomfort)6 months
Growth (length for age, weight for age, and length for weight)6 month
Changes in folate, vitamin B12, methyl malonic acid, and homocysteine concentration6 months
Compare the change in plasma MBL between the intervention groups6 months

We will compare the change in plasma MBL between those who have been given 2 RDA of vitamin B12 and/or folic acid with those who were given placebo in a subsample of 256 children.

Vitamin D statusBaseline blood samples

We will measure vitamin D (25-hydroxy vitamin D) in all children at baseline to describe the vitamin D status and the proportion with vitamin D deficiency.

Developmental MilestonesEnd study, i.e. after 6 months of vitamin B12 and/or folic acid administration

Developmental milestones. The developmental milestones will be measured using the ASQ-3. ASQ-3 is an easily administered and comprehensive checklist consisting of 30 items measuring skills in 5 different domains; Communication, Gross Motor, Fine Motor, Personal-Social and Problem-Solving. The questionnaires are divided into two-month intervals for use with children 4-60 months of age, and scores are normed to indicate whether children are developing age-appropriately.

Measure the association between pneumonia incidence and the plasma mannose binding lectin (MBL) concentrationBaseline blood samples
Measure the exposure to Cryptosporidium sppBaseline blood samples

We will measure the exposure to Cryptosporidium spp. in Indian children aged 6-30 months by measurement of antibodies to recombinant gp15, a conserved surface protein in plasma samples taken at baseline.

Measure the association between the antibody response to Cryptosporidium and plasma MBLBaseline blood samples
Vitamin D status and the risk for respiratory infectionsBaseline samples and 6 months follow up

We will measure the vitamin D status at baseline and assess to what extent it predicts the risk of subsequent respiratory tract infections over the next 6 months.

Trial Locations

Locations (1)

Society for Essential Health Action and Training

🇮🇳

New Delhi, Delhi, India

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