Folic Acid and Vitamin B12 in Young Indian Children

July 27, 2015 updated by: Tor A. Strand

Routine Administration of Folic Acid and Vitamin B12 to Prevent Childhood Infections 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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1000

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 months to 2 years (CHILD)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: FACTORIAL
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
PLACEBO_COMPARATOR: A
Placebo dietary supplement
Dietary supplement: Placebo
Placebo with no active ingredients
EXPERIMENTAL: B
Folic acid
Dietary supplement: Folic Acid
150µgm/day for 6 months in children older than 11 months and 80µgm in 6 to 11 months.
Other Names:
  • Folate
EXPERIMENTAL: C
Vitamin B12
Dietary supplement: Vitamin B12
1.8µgm/day for 6 months in children older than 11 months and 0.5µgm in 6 to 11 months.
Other Names:
  • Cobalamin
EXPERIMENTAL: D
Folic acid and Vitamin B12
Dietary supplement: Folic acid and vitamin B12
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Number of episodes diarrhea (all, severe, prolonged) and pneumonia (ALRI, Clinical pneumonia)
Time Frame: 6 months
6 months
Prevalence of diarrhea
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Growth (length for age, weight for age, and length for weight)
Time Frame: 6 month
6 month
Adverse events (vomiting and gastric discomfort)
Time Frame: 6 months
6 months
Changes in folate, vitamin B12, methyl malonic acid, and homocysteine concentration
Time Frame: 6 months
6 months
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.
End study, i.e. after 6 months of vitamin B12 and/or folic acid administration
Measure the association between pneumonia incidence and the plasma mannose binding lectin (MBL) concentration
Time Frame: Baseline blood samples
Baseline blood samples
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.
Baseline blood samples
Measure the association between the antibody response to Cryptosporidium and plasma MBL
Time Frame: Baseline blood samples
Baseline blood samples
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.
6 months
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.
Baseline blood samples
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.
Baseline samples and 6 months follow up

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Tor A. Strand

Collaborators

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

Investigators

  • Principal Investigator: Tor A Strand, MD, PhD, University of Bergen
  • Principal Investigator: Sunita Taneja, MBBS, PhD, Society for Essential Health Action and Training

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2010

Primary Completion (ACTUAL)

September 1, 2011

Study Completion (ACTUAL)

September 1, 2011

Study Registration Dates

First Submitted

July 16, 2008

First Submitted That Met QC Criteria

July 16, 2008

First Posted (ESTIMATE)

July 17, 2008

Study Record Updates

Last Update Posted (ESTIMATE)

July 28, 2015

Last Update Submitted That Met QC Criteria

July 27, 2015

Last Verified

July 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • RCN172226

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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