Folic Acid and Vitamin B12 in Young Indian Children

Pneumonia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00717730
• Other study ID #: RCN172226
• Status: Completed
• Phase: Phase 2
• First received: July 16, 2008
• Last updated: July 27, 2015
• Start date: January 2010
• Est. completion date: September 2011

Study information

• Verified date: July 2015
• Source: Centre For International Health
• Contact: n/a
• Is FDA regulated: No
• Health authority: Norway:National Committee for Medical and Health Research Ethics
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 1000
• Est. completion date: September 2011
• Est. primary completion date: September 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 6 Months to 30 Months

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Diarrhea
• Pneumonia

Intervention

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.
• Placebo
Placebo with no active ingredients
• 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.

Locations

Country	Name	City	State
India	Society for Essential Health Action and Training	New Delhi	Delhi

Sponsors (3)

Lead Sponsor	Collaborator
Tor A. Strand	Society for Essential Health Action and Training, New Delhi, India, Thrasher Research Fund

Country where clinical trial is conducted

India, 

References & Publications (11)

Allen LH. Multiple micronutrients in pregnancy and lactation: an overview. Am J Clin Nutr. 2005 May;81(5):1206S-1212S. Review. — View Citation

Fawzi WW, Msamanga GI, Spiegelman D, Urassa EJ, McGrath N, Mwakagile D, Antelman G, Mbise R, Herrera G, Kapiga S, Willett W, Hunter DJ. Randomised trial of effects of vitamin supplements on pregnancy outcomes and T cell counts in HIV-1-infected women in Tanzania. Lancet. 1998 May 16;351(9114):1477-82. — View Citation

Fawzi WW, Msamanga GI, Urassa W, Hertzmark E, Petraro P, Willett WC, Spiegelman D. Vitamins and perinatal outcomes among HIV-negative women in Tanzania. N Engl J Med. 2007 Apr 5;356(14):1423-31. — View Citation

Khambalia A, Latulippe ME, Campos C, Merlos C, Villalpando S, Picciano MF, O'connor DL. Milk folate secretion is not impaired during iron deficiency in humans. J Nutr. 2006 Oct;136(10):2617-24. — View Citation

Sazawal S, Black RE, Ramsan M, Chwaya HM, Stoltzfus RJ, Dutta A, Dhingra U, Kabole I, Deb S, Othman MK, Kabole FM. Effects of routine prophylactic supplementation with iron and folic acid on admission to hospital and mortality in preschool children in a high malaria transmission setting: community-based, randomised, placebo-controlled trial. Lancet. 2006 Jan 14;367(9505):133-43. Erratum in: Lancet. 2006 Jan 28;367(9507):302. — View Citation

Sazawal S, Dhingra U, Dhingra P, Hiremath G, Kumar J, Sarkar A, Menon VP, Black RE. Effects of fortified milk on morbidity in young children in north India: community based, randomised, double masked placebo controlled trial. BMJ. 2007 Jan 20;334(7585):140. Epub 2006 Nov 28. — View Citation

Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr. 2008 Mar;87(3):517-33. — View Citation

Strand TA, Taneja S, Bhandari N, Refsum H, Ueland PM, Gjessing HK, Bahl R, Schneede J, Bhan MK, Sommerfelt H. Folate, but not vitamin B-12 status, predicts respiratory morbidity in north Indian children. Am J Clin Nutr. 2007 Jul;86(1):139-44. — View Citation

Tamura T, Yoshimura Y, Arakawa T. Human milk folate and folate status in lactating mothers and their infants. Am J Clin Nutr. 1980 Feb;33(2):193-7. — View Citation

Taneja S, Bhandari N, Strand TA, Sommerfelt H, Refsum H, Ueland PM, Schneede J, Bahl R, Bhan MK. Cobalamin and folate status in infants and young children in a low-to-middle income community in India. Am J Clin Nutr. 2007 Nov;86(5):1302-9. — View Citation

Tielsch JM, Khatry SK, Stoltzfus RJ, Katz J, LeClerq SC, Adhikari R, Mullany LC, Shresta S, Black RE. Effect of routine prophylactic supplementation with iron and folic acid on preschool child mortality in southern Nepal: community-based, cluster-randomised, placebo-controlled trial. Lancet. 2006 Jan 14;367(9505):144-52. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of episodes diarrhea (all, severe, prolonged) and pneumonia (ALRI, Clinical pneumonia)		6 months	No
Primary	Prevalence of diarrhea		6 months	No
Secondary	Growth (length for age, weight for age, and length for weight)		6 month	No
Secondary	Adverse events (vomiting and gastric discomfort)		6 months	Yes
Secondary	Changes in folate, vitamin B12, methyl malonic acid, and homocysteine concentration		6 months	No
Secondary	Developmental Milestones	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	No
Secondary	Measure the association between pneumonia incidence and the plasma mannose binding lectin (MBL) concentration		Baseline blood samples	No
Secondary	Measure the exposure to Cryptosporidium spp	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	No
Secondary	Measure the association between the antibody response to Cryptosporidium and plasma MBL		Baseline blood samples	No
Secondary	Compare the change in plasma MBL between the intervention groups	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	No
Secondary	Vitamin D status	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	No
Secondary	Vitamin D status and the risk for respiratory infections	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	No