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Folic Acid and Vitamin B12 in Young Indian Children

This study has been completed.
Sponsor:
Collaborators:
Society for Essential Health Action and Training, New Delhi, India
Thrasher Research Fund
Information provided by (Responsible Party):
Tor A. Strand, Centre For International Health
ClinicalTrials.gov Identifier:
NCT00717730
First received: July 16, 2008
Last updated: November 3, 2011
Last verified: November 2011
  Purpose

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.


Condition Intervention Phase
Diarrhea
Pneumonia
Dietary Supplement: Folic Acid
Dietary Supplement: Vitamin B12
Dietary Supplement: Placebo
Dietary Supplement: Folic acid and vitamin B12
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Routine Administration of Folic Acid and Vitamin B12 to Prevent Childhood Infections in Young Indian Children

Resource links provided by NLM:


Further study details as provided by Centre For International Health:

Primary Outcome Measures:
  • Number of episodes diarrhea (all, severe, prolonged) and pneumonia (ALRI, Clinical pneumonia) [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Prevalence of diarrhea [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Growth (length for age, weight for age, and length for weight) [ Time Frame: 6 month ] [ Designated as safety issue: No ]
  • Adverse events (vomiting and gastric discomfort) [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
  • Changes in folate, vitamin B12, methyl malonic acid, and homocysteine concentration [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Developmental Milestones [ Time Frame: End study, i.e. after 6 months of vitamin B12 and/or folic acid administration ] [ Designated as safety issue: No ]
    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) concentration [ Time Frame: Baseline blood samples ] [ Designated as safety issue: No ]
  • Measure the exposure to Cryptosporidium spp [ Time Frame: Baseline blood samples ] [ Designated as safety issue: No ]
    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 MBL [ Time Frame: Baseline blood samples ] [ Designated as safety issue: No ]
  • Compare the change in plasma MBL between the intervention groups [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 status [ Time Frame: Baseline blood samples ] [ Designated as safety issue: No ]
    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.

  • Vitamin D status and the risk for respiratory infections [ Time Frame: Baseline samples and 6 months follow up ] [ Designated as safety issue: No ]
    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.


Enrollment: 1000
Study Start Date: January 2010
Study Completion Date: September 2011
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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.

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

Ages Eligible for Study:   6 Months to 30 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00717730

Locations
India
Society for Essential Health Action and Training
New Delhi, Delhi, India
Sponsors and Collaborators
Tor A. Strand
Society for Essential Health Action and Training, New Delhi, India
Thrasher Research Fund
Investigators
Principal Investigator: Tor A Strand, MD, PhD University of Bergen
Principal Investigator: Sunita Taneja, MBBS, PhD Society for Essential Health Action and Training
  More Information

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Tor A. Strand, Professor II, Centre For International Health
ClinicalTrials.gov Identifier: NCT00717730     History of Changes
Other Study ID Numbers: RCN172226
Study First Received: July 16, 2008
Last Updated: November 3, 2011
Health Authority: Norway:National Committee for Medical and Health Research Ethics

Keywords provided by Centre For International Health:
Nutrition
Children
Folate
Vitamin B12
India
Homocysteine
Methyl Malonic Acid

Additional relevant MeSH terms:
Folic Acid
Hydroxocobalamin
Vitamin B 12
Vitamin B Complex
Vitamins
Growth Substances
Hematinics
Hematologic Agents
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on November 24, 2014