Folic Acid and Vitamin B12 in Young Indian Children

NCT00717730 | Completed Phase 2 DMC

• 1 other identifier: RCN172226
• Study Type: interventional
• Target: 1,000
• Locations: 1 country
• Sites: 1

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.

Conditions

Diarrhea; Pneumonia

Keywords

Nutrition; Children; Folate; Vitamin B12; India; Homocysteine; Methyl Malonic Acid

Outcome Measures

Primary Outcomes (2)

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

  6 months

• Prevalence of diarrhea

  6 months

Secondary Outcomes (10)

• Growth (length for age, weight for age, and length for weight)

  6 month

• Adverse events (vomiting and gastric discomfort)

  6 months

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

  6 months

• Developmental Milestones

  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

  Baseline blood samples

Study Arms (4)

A

PLACEBO COMPARATOR

Placebo dietary supplement

Dietary Supplement: Placebo

B

EXPERIMENTAL

Folic acid

Dietary Supplement: Folic Acid

C

EXPERIMENTAL

Vitamin B12

Dietary Supplement: Vitamin B12

D

EXPERIMENTAL

Folic acid and Vitamin B12

Dietary Supplement: Folic acid and vitamin B12

Interventions

Folic Acid DIETARY_SUPPLEMENT

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

Also known as: Folate

B

Vitamin B12 DIETARY_SUPPLEMENT

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

Also known as: Cobalamin

C

Placebo DIETARY_SUPPLEMENT

Placebo with no active ingredients

A

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.

D

Eligibility Criteria

• Age: 6 Months - 30 Months
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• Age: 6 to 30 months
• Either sex
• Likely to reside in area for next 6 months

You may not qualify if:

• 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).

Sponsors & Collaborators

• Tor A. Strand: lead
• Society for Essential Health Action and Training, New Delhi, India: collaborator
• Thrasher Research Fund: collaborator

Study Sites (1)

Society for Essential Health Action and Training

New Delhi, National Capital Territory of Delhi, India

Location

Related Publications (19)

• 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. doi: 10.1093/ajcn/86.5.1302.

  PMID: 17991639 BACKGROUND

• 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. doi: 10.1093/ajcn/86.1.139.

  PMID: 17616773 BACKGROUND

• Allen LH. Multiple micronutrients in pregnancy and lactation: an overview. Am J Clin Nutr. 2005 May;81(5):1206S-1212S. doi: 10.1093/ajcn/81.5.1206.

  PMID: 15883453 BACKGROUND

• Smith AD, Kim YI, Refsum H. Is folic acid good for everyone? Am J Clin Nutr. 2008 Mar;87(3):517-33. doi: 10.1093/ajcn/87.3.517.

  PMID: 18326588 BACKGROUND

• 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. doi: 10.1136/bmj.39035.482396.55. Epub 2006 Nov 28.

  PMID: 17132678 BACKGROUND

• 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. doi: 10.1016/S0140-6736(06)67963-4.

  PMID: 16413878 BACKGROUND

• 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. doi: 10.1016/s0140-6736(98)04197-x.

  PMID: 9605804 BACKGROUND

• 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. doi: 10.1016/S0140-6736(06)67962-2.

  PMID: 16413877 BACKGROUND

• 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. doi: 10.1056/NEJMoa064868.

  PMID: 17409323 BACKGROUND

• 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. doi: 10.1093/ajcn/33.2.193.

  PMID: 7355792 BACKGROUND

• 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. doi: 10.1093/jn/136.10.2617.

  PMID: 16988136 BACKGROUND

• Chowdhury R, Taneja S, Kvestad I, Hysing M, Bhandari N, Strand TA. Vitamin D status in early childhood is not associated with cognitive development and linear growth at 6-9 years of age in North Indian children: a cohort study. Nutr J. 2020 Feb 10;19(1):14. doi: 10.1186/s12937-020-00530-2.

  PMID: 32041632 DERIVED

• Kvestad I, Taneja S, Upadhyay RP, Hysing M, Bhandari N, Strand TA. Vitamin B12, Folate, and Cognition in 6- to 9-Year-Olds: A Randomized Controlled Trial. Pediatrics. 2020 Mar;145(3):e20192316. doi: 10.1542/peds.2019-2316. Epub 2020 Feb 4.

  PMID: 32019814 DERIVED

• Winje BA, Kvestad I, Krishnamachari S, Manji K, Taneja S, Bellinger DC, Bhandari N, Bisht S, Darling AM, Duggan CP, Fawzi W, Hysing M, Kumar T, Kurpad AV, Sudfeld CR, Svensen E, Thomas S, Strand TA. Does early vitamin B12 supplementation improve neurodevelopment and cognitive function in childhood and into school age: a study protocol for extended follow-ups from randomised controlled trials in India and Tanzania. BMJ Open. 2018 Feb 22;8(2):e018962. doi: 10.1136/bmjopen-2017-018962.

  PMID: 29472265 DERIVED

• Chowdhury R, Taneja S, Bhandari N, Kvestad I, Strand TA, Bhan MK. Vitamin-D status and neurodevelopment and growth in young north Indian children: a secondary data analysis. Nutr J. 2017 Sep 18;16(1):59. doi: 10.1186/s12937-017-0285-y.

  PMID: 28923060 DERIVED

• Kumar T, Taneja S, Sachdev HPS, Refsum H, Yajnik CS, Bhandari N, Strand TA; Study Group. Supplementation of vitamin B12 or folic acid on hemoglobin concentration in children 6-36 months of age: A randomized placebo controlled trial. Clin Nutr. 2017 Aug;36(4):986-991. doi: 10.1016/j.clnu.2016.07.002. Epub 2016 Jul 18.

  PMID: 27486122 DERIVED

• Kvestad I, Taneja S, Kumar T, Hysing M, Refsum H, Yajnik CS, Bhandari N, Strand TA; Folate and Vitamin B12 Study Group. Vitamin B12 and Folic Acid Improve Gross Motor and Problem-Solving Skills in Young North Indian Children: A Randomized Placebo-Controlled Trial. PLoS One. 2015 Jun 22;10(6):e0129915. doi: 10.1371/journal.pone.0129915. eCollection 2015.

  PMID: 26098427 DERIVED

• Strand TA, Taneja S, Kumar T, Manger MS, Refsum H, Yajnik CS, Bhandari N. Vitamin B-12, folic acid, and growth in 6- to 30-month-old children: a randomized controlled trial. Pediatrics. 2015 Apr;135(4):e918-26. doi: 10.1542/peds.2014-1848.

  PMID: 25802345 DERIVED

• Taneja S, Strand TA, Kumar T, Mahesh M, Mohan S, Manger MS, Refsum H, Yajnik CS, Bhandari N. Folic acid and vitamin B-12 supplementation and common infections in 6-30-mo-old children in India: a randomized placebo-controlled trial. Am J Clin Nutr. 2013 Sep;98(3):731-7. doi: 10.3945/ajcn.113.059592. Epub 2013 Jul 31.

  PMID: 23902779 DERIVED

MeSH Terms

Conditions

Diarrhea; Pneumonia

Interventions

Folic Acid; Vitamin B 12

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Corrinoids; Tetrapyrroles; Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds, 4 or More Rings; Macrocyclic Compounds; Polycyclic Compounds

Study Officials

• Tor A Strand, MD, PhD

  University of Bergen

  PRINCIPAL INVESTIGATOR

• Sunita Taneja, MBBS, PhD

  Society for Essential Health Action and Training

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor II

Study Record Dates

• First Submitted: July 16, 2008
• First Posted: July 17, 2008
• Study Start: January 1, 2010
• Primary Completion: September 1, 2011
• Study Completion: September 1, 2011
• Last Updated: July 28, 2015

Record last verified: 2015-07

Locations

IN (1)