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Vitamin B12, Neurodevelopment and Growth in Nepal (BeLive)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT02272842
Recruitment Status : Active, not recruiting
First Posted : October 23, 2014
Results First Posted : May 25, 2021
Last Update Posted : May 25, 2021
Tribhuvan University, Nepal
NORCE Norwegian Research Centre AS
Information provided by (Responsible Party):
Centre For International Health

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.

Condition or disease Intervention/treatment Phase
Development Vitamin Deficiency Malnutrition Dietary Supplement: Vitamin B12 Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: The Effect of Vitamin B12 Supplementation in Nepali Infants on Growth and Development
Actual Study Start Date : April 20, 2015
Actual Primary Completion Date : February 28, 2018
Estimated Study Completion Date : February 28, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: B Vitamins

Arm Intervention/treatment
Experimental: Vitamin B12
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
Vitamin B12 in a multivitamin paste.
Other Name: Cobalamin

Placebo Comparator: Placebo
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
Vitamin B12 in a multivitamin paste.
Other Name: Cobalamin

Primary Outcome Measures :
  1. The Bayley Scales of Infant Development Version 3 [ Time Frame: 12 months ]
    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), 95% of the population have scores between 70 and 130 (theoretical max/means 0/200). The higher scores, the better neurodevelopment, the scale is normalized on age.

  2. Hemoglobin Concentration [ Time Frame: 12 months ]
    Change in hemoglobin concentration from baseline to end study.

Secondary Outcome Measures :
  1. Growth Velocity Over the First Six Months of Supplementation [ Time Frame: 12 months ]
    length and weight growth velocity z scores during supplementation z-scores, growth velocity. theoretical values -10 to 10 The higher the value, the faster the growth.

  2. Predictors for Neurodevelopment in Young Nepali Children [ Time Frame: 12 months ]
    Using the collected data, identify morbidity, stimulation, nutrition, socioeconomic related predictors for neurodevelopment.

  3. Identify Subgroups of Children Who Benefit From Vitamin B12 Supplementation [ Time Frame: 12 months ]
    Based on selected baseline variables we will identify subgroups who benefit from vitamin B12 supplementation

  4. The Effect of Vitamin B12 Supplementation on Markers of Vitamin B Status [ Time Frame: 12 months ]
    We will draw a blood sample at study start and at end study to measure to what extent vitamin status is altered.

  5. Neurodevelopment Measured by Other Tools. [ Time Frame: 12 months ]
    We will measure to what extent vitamin B12 supplementation improves neurodevelopment measured by other tools such as the Ages and Stages Questionnaire (version 3) and the NEPSY II test.

  6. Immediate Adverse Effects of the Intervention [ Time Frame: 12 months ]
    We will investigate side effects such as pain, nausea, vomiting, regurgitation, allergic reactions and others after each dose of the intervention.

  7. Leucocyte Telomere Length [ Time Frame: 12 months ]
    Relative leucocyte telomere length at end of the study period. Estimated by real-time PCR analysis

  8. Sleep Duration [ Time Frame: 12 months ]
    Using actigraph and a structured questionaire on all children at baseline and at end of study measure the extent to which the intervention affects sleep.

Other Outcome Measures:
  1. Extended Followup: Neurodevelopment [ Time Frame: 3 years ]
    We will follow the cohort beyond the planned (and funded) project period and measure neurodevelopment using appropriate tests such as the Wechsler tests

  2. Surrogate Markers for Neurodevelopment [ Time Frame: 2 years ]
    If funding allows, measure other markers related to neurodevelopment such as Brain Derived Neurotrophic Factor

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   6 Months to 11 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Age 6 to 11 months
  • Stunted
  • Availability of informed verbal consent
  • Plan to reside in the area for the next 12 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.
  • Lack of consent
  • Taking B vitamin supplements that include vitamin B12.
  • Severe anemia (Hb < 7 g/dL). This would be a temporary exclusion and the children will be enrolled if they are successfully treated.
  • Ongoing acute infection with fever or infection that requires medical treatment. This would be a temporary exclusion and the children will be enrolled after recovery.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT02272842

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Siddhi Memorial Hospital (SMH),Bhelukhel, Bhimsensthan
Bhaktapur, Nepal, P.O.Box 40
Sponsors and Collaborators
Centre For International Health
Tribhuvan University, Nepal
NORCE Norwegian Research Centre AS
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Principal Investigator: Prakash S Shrestha, MD Tribhuvan University, Nepal
Principal Investigator: Tor A Strand, MD/PhD Innlandet Hospital Trust / University of Bergen
  Study Documents (Full-Text)

Documents provided by Centre For International Health:
Study Protocol  [PDF] April 2, 2020
Statistical Analysis Plan  [PDF] October 15, 2019

Additional Information:
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Centre For International Health Identifier: NCT02272842    
Other Study ID Numbers: 808734
U1111-1161-5187 ( Other Identifier: WHO )
First Posted: October 23, 2014    Key Record Dates
Results First Posted: May 25, 2021
Last Update Posted: May 25, 2021
Last Verified: May 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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 (, or by contacting the Department of Global Health and Primary Care at the University of Bergen (
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (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
Keywords provided by Centre For International Health:
Additional relevant MeSH terms:
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Nutrition Disorders
Deficiency Diseases
Vitamin B 12
Physiological Effects of Drugs
Vitamin B Complex