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Completed

NCT Number: NCT00717730

Folic Acid and Vitamin B12 in Young Indian Children

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.

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Key information

Age range

6 month–30 month

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Society for Essential Health Action and Training

New Delhi, National Capital Territory of Delhi, India

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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).

Treatment and study plan

Folic Acid

Dietary Supplement

150µgm/day for 6 months in children older than 11 months and 80µgm in 6 to 11 months.

Other names: Folate

Vitamin B12

Dietary Supplement

1.8µgm/day for 6 months in children older than 11 months and 0.5µgm in 6 to 11 months.

Other names: Cobalamin

Placebo

Dietary Supplement

Placebo with no active ingredients

Folic acid and vitamin B12

Dietary Supplement

Folic acid 150µgm/day for 6 months in children older than 11 months and 80µgm in 6 to 11 months vitamin B12 1.8µgm/day for 6 months in children older than 11 months and 0.5µgm in 6 to 11 months.

Primary outcomes

  1. Number of episodes diarrhea (all, severe, prolonged) and pneumonia (ALRI, Clinical pneumonia)

    Time frame: 6 months

  2. Prevalence of diarrhea

    Time frame: 6 months

Secondary outcomes

  1. Growth (length for age, weight for age, and length for weight)

    Time frame: 6 month

  2. Adverse events (vomiting and gastric discomfort)

    Time frame: 6 months

  3. Changes in folate, vitamin B12, methyl malonic acid, and homocysteine concentration

    Time frame: 6 months

  4. Developmental Milestones

    Time frame: End 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.

  5. Measure the association between pneumonia incidence and the plasma mannose binding lectin (MBL) concentration

    Time frame: Baseline blood samples

  6. Measure the exposure to Cryptosporidium spp

    Time frame: Baseline 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.

  7. Measure the association between the antibody response to Cryptosporidium and plasma MBL

    Time frame: Baseline blood samples

  8. Compare the change in plasma MBL between the intervention groups

    Time frame: 6 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.

  9. Vitamin D status

    Time frame: Baseline 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.

  10. Vitamin D status and the risk for respiratory infections

    Time frame: Baseline 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.

Sponsors and collaborators

Lead sponsor

Tor A. Strand

Other

Collaborators

  • Society for Essential Health Action and Training, New Delhi, India
  • Thrasher Research Fund

Registry information

Official study title

Routine Administration of Folic Acid and Vitamin B12 to Prevent Childhood Infections in Young Indian Children

Important dates

Study start
2010
Primary completion
2011
Study completion
2011
First posted
Jul 17, 2008
Registry last updated
Jul 28, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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