Clinical trial NCT00717730: Folic Acid and Vitamin B12 in Young Indian Children
Official title: Routine Administration of Folic Acid and Vitamin B12 to Prevent Childhood Infections in Young Indian Children
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Diarrhea
Pneumonia
Keywords: Nutrition
Children
Folate
Vitamin B12
India
Homocysteine
Methyl Malonic Acid
Lead sponsor: Centre For International Health
Sponsor class: OTHER
Collaborators: name: Society for Essential Health Action and Training, New Delhi, India
name: Thrasher Research Fund
First posted: 2008-07-17
Enrollment: 1000
Sex: ALL
Minimum age (years): 6
Maximum age (years): 30
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Number of episodes diarrhea (all, severe, prolonged) and pneumonia (ALRI, Clinical pneumonia)
timeFrame: 6 months
measure: Prevalence of diarrhea
timeFrame: 6 months
Secondary outcomes:
measure: Growth (length for age, weight for age, and length for weight)
timeFrame: 6 month
measure: Adverse events (vomiting and gastric discomfort)
timeFrame: 6 months
measure: Changes in folate, vitamin B12, methyl malonic acid, and homocysteine concentration
timeFrame: 6 months
measure: Developmental Milestones
timeFrame: End study, i.e. after 6 months of vitamin B12 and/or folic acid administration
measure: Measure the association between pneumonia incidence and the plasma mannose binding lectin (MBL) concentration
timeFrame: Baseline blood samples
measure: Measure the exposure to Cryptosporidium spp
timeFrame: Baseline blood samples
measure: Measure the association between the antibody response to Cryptosporidium and plasma MBL
timeFrame: Baseline blood samples
measure: Compare the change in plasma MBL between the intervention groups
timeFrame: 6 months
measure: Vitamin D status
timeFrame: Baseline blood samples
measure: Vitamin D status and the risk for respiratory infections
timeFrame: Baseline samples and 6 months follow up
Other outcomes:
Locations:
city: New Delhi
country: India
facility: Society for Essential Health Action and Training
state: Delhi
Study officials:
affiliation: University of Bergen
name: Tor A Strand, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Society for Essential Health Action and Training
name: Sunita Taneja, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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