NCT02272842

Brief Summary

Rationale: Globally, vitamin B12 deficiency is one of the most common micronutrient deficiencies. The only relevant source of Vitamin B12 is animal-source foods. Vitamin B12 is crucial for normal cell division and is necessary for brain growth as well as for the maintenance of its normal function. Deficiency is also associated with impaired growth. In a previous study, we demonstrated that vitamin B12 administration over a period of six months enhanced growth, and scores on a neuro-developmental test in young Indian children. However, the overall effect was small and, for the developmental scores significant only in those that were malnourished at the start of the study. Our findings need to be verified in trials targeting younger, malnourished children and with longer supplementation time. Hypothesis: This proposed study will test three hypotheses; to measure to what extent 2 recommended daily allowances (RDA) of vitamin B12 administration for one year to stunted children improves; 1) growth, 2) neurodevelopment, and 3) hemoglobin concentration. Study design: Randomized placebo-controlled trial. Half of the children will receive a paste containing vitamin B12, the other half the same paste but without vitamin B12. Study participants and site: 600 malnourished infants in Bhaktapur municipality in Nepal. In this population we have demonstrated that vitamin B12 deficiency and poor growth is common in early childhood. Intervention: Daily administration of a paste containing vitamin B12 or placebo for 12 months Data: The main outcomes of this study are scores on developmental assessments tools and growth measured every month for 12 months.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
600

participants targeted

Target at P75+ for phase_2

Timeline
Completed

Started Apr 2015

Longer than P75 for phase_2

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

October 21, 2014

Completed
2 days until next milestone

First Posted

Study publicly available on registry

October 23, 2014

Completed
6 months until next milestone

Study Start

First participant enrolled

April 20, 2015

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 28, 2018

Completed
3.2 years until next milestone

Results Posted

Study results publicly available

May 25, 2021

Completed
3.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

December 28, 2024

Completed
Last Updated

September 18, 2023

Status Verified

July 1, 2022

Enrollment Period

2.9 years

First QC Date

October 21, 2014

Results QC Date

July 18, 2018

Last Update Submit

August 29, 2023

Conditions

DevelopmentVitamin DeficiencyMalnutrition

Keywords

NepalCobalaminNeurodevelopmentStuntingGrowth

Outcome Measures

Primary Outcomes (2)

  • The Bayley Scales of Infant Development Version 3

    Cognitive, Fine Motor, Gross Motor, Receptive language, and Expressive language scaled scores of the Bayley Scales of Infant Development version 3. This scale measures different aspects of neurodevelopment. The mean (SD) scores are usually 100 (15), and 95% of the population has scores between 70 and 130 (theoretical max/means 0/200). The higher scores, the better neurodevelopment; the scale is normalized on age.

    12 months

  • Hemoglobin Concentration

    Change in hemoglobin concentration from baseline to end study.

    12 months

Secondary Outcomes (8)

  • Growth Velocity Over the First Six Months of Supplementation

    12 months

  • Predictors for Neurodevelopment in Young Nepali Children

    12 months

  • Identify Subgroups of Children Who Benefit From Vitamin B12 Supplementation

    12 months

  • The Effect of Vitamin B12 Supplementation on Markers of Vitamin B Status

    12 months

  • Neurodevelopment Measured by Other Tools.

    12 months

  • +3 more secondary outcomes

Other Outcomes (2)

  • Extended Followup: Neurodevelopment (IQ)

    3 years

  • Surrogate Markers for Neurodevelopment

    2 years

Study Arms (2)

Vitamin B12

EXPERIMENTAL

A paste containing vitamin B12 2µg per 10 mL administered every day. The paste also contains 1 RDA of several other vitamins. The paste is produced by Compact (Norway / India)

Dietary Supplement: Vitamin B12

Placebo

PLACEBO COMPARATOR

A paste containing no vitamin administered every day. The paste also contains 1 RDA of several vitamins, but no vitamin B12. The paste is produced by Compact (Norway / India)

Dietary Supplement: Vitamin B12

Interventions

Vitamin B12DIETARY_SUPPLEMENT

Vitamin B12 in a multivitamin paste.

Also known as: Cobalamin
PlaceboVitamin B12

Eligibility Criteria

Age6 Months - 11 Months
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Age 6 to 11 months
  • Stunted
  • Availability of informed verbal consent
  • Plan to reside in the area for the next 12 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.
  • Lack of consent
  • Taking B vitamin supplements that include vitamin B12.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan

Bhaktapur, P.O.Box 40, Nepal

Location

Related Publications (9)

  • 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: 23902779BACKGROUND

  • Strand TA, Taneja S, Ueland PM, Refsum H, Bahl R, Schneede J, Sommerfelt H, Bhandari N. Cobalamin and folate status predicts mental development scores in North Indian children 12-18 mo of age. Am J Clin Nutr. 2013 Feb;97(2):310-7. doi: 10.3945/ajcn.111.032268. Epub 2013 Jan 2.

    PMID: 23283502BACKGROUND

  • Black MM. Effects of vitamin B12 and folate deficiency on brain development in children. Food Nutr Bull. 2008 Jun;29(2 Suppl):S126-31. doi: 10.1177/15648265080292S117.

    PMID: 18709887BACKGROUND

  • Black MM. Micronutrient deficiencies and cognitive functioning. J Nutr. 2003 Nov;133(11 Suppl 2):3927S-3931S. doi: 10.1093/jn/133.11.3927S.

    PMID: 14672291BACKGROUND

  • Ulak M, Kvestad I, Chandyo RK, Schwinger C, Basnet S, Shrestha M, Ranjitkar S, Nguyen LV, Corona-Perez D, De Vivo I, Ueland PM, McCann A, Strand TA. The Effect of Vitamin B12 Supplementation on Leukocyte Telomere Length in Mildly Stunted Nepalese Children: A Secondary Outcome of a Randomized Controlled Trial. J Nutr. 2024 Aug;154(8):2543-2550. doi: 10.1016/j.tjnut.2023.10.015. Epub 2023 Oct 31.

    PMID: 37918674DERIVED

  • Chandyo RK, Schwinger C, Kvestad I, Ulak M, Ranjitkar S, Shrestha M, Nguyen LV, Corona-Perez D, DeVivo I, Shrestha L, Strand TA. The association between household biomass fuel use and leukocyte telomere length among toddlers in Bhaktapur, Nepal. J Expo Sci Environ Epidemiol. 2023 May;33(3):448-454. doi: 10.1038/s41370-022-00474-1. Epub 2022 Sep 22.

    PMID: 36138138DERIVED

  • Hysing M, Strand TA, Chandyo RK, Ulak M, Ranjitkar S, Schwinger C, Shrestha M, Kvestad I. The effect of vitamin B12-supplementation on actigraphy measured sleep pattern; a randomized control trial. Clin Nutr. 2022 Feb;41(2):307-312. doi: 10.1016/j.clnu.2021.11.040. Epub 2021 Dec 6.

    PMID: 34999324DERIVED

  • Strand TA, Ulak M, Hysing M, Ranjitkar S, Kvestad I, Shrestha M, Ueland PM, McCann A, Shrestha PS, Shrestha LS, Chandyo RK. Effects of vitamin B12 supplementation on neurodevelopment and growth in Nepalese Infants: A randomized controlled trial. PLoS Med. 2020 Dec 1;17(12):e1003430. doi: 10.1371/journal.pmed.1003430. eCollection 2020 Dec.

    PMID: 33259482DERIVED

  • Strand TA, Ulak M, Chandyo RK, Kvestad I, Hysing M, Shrestha M, Basnet S, Ranjitkar S, Shrestha L, Shrestha PS. The effect of vitamin B12 supplementation in Nepalese infants on growth and development: study protocol for a randomized controlled trial. Trials. 2017 Apr 21;18(1):187. doi: 10.1186/s13063-017-1937-0.

    PMID: 28431557DERIVED

Related Links

MeSH Terms

Conditions

AvitaminosisMalnutritionGrowth Disorders

Interventions

Vitamin B 12

Condition Hierarchy (Ancestors)

Deficiency DiseasesNutrition DisordersNutritional and Metabolic DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

CorrinoidsTetrapyrrolesPyrrolesAzolesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsHeterocyclic Compounds, 4 or More RingsHeterocyclic Compounds, Fused-RingMacrocyclic CompoundsPolycyclic Compounds

Results Point of Contact

Title
Tor Strand
Organization
Innlandet Hospital Trust
tors@me.com
+4790971086

Study Officials

  • Prakash S Shrestha, MD

    Tribhuvan University, Nepal

    PRINCIPAL INVESTIGATOR

  • Tor A Strand, MD/PhD

    Innlandet Hospital Trust / University of Bergen

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restrictive Agreement
No

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
PREVENTION
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 21, 2014

First Posted

October 23, 2014

Study Start

April 20, 2015

Primary Completion

February 28, 2018

Study Completion

December 28, 2024

Last Updated

September 18, 2023

Results First Posted

May 25, 2021

Record last verified: 2022-07

Data Sharing

IPD Sharing
Will share

Data available on request. In order to meet ethical requirements for the use of confidential patient data, requests must be approved by the Nepal Health Research Council (NHRC) and the Regional Committee for Medical and Health Research Ethics in Norway. Requests for data should be sent to the authors, by contacting NHRC (http://nhrc.gov.np), or by contacting the Department of Global Health and Primary Care at the University of Bergen (post@igs.uib.no).

Shared Documents
STUDY PROTOCOL, SAP, ICF, CSR
Time Frame
Upon publication of the main outcomes.
Access Criteria
The protocols and the plan of analyses will be available with the main publication. IPD will be available following an application process which involves the ethical committees in Norway and Nepal

Locations

NE(1)