Early Infant Micronutrition and Development

NCT ID: NCT05005897

Last Updated: 2023-04-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2/PHASE3

Total Enrollment

600 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-12-08

Study Completion Date

2029-10-15

Brief Summary

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Globally, vitamin B12 deficiency is one of the most common micronutrient deficiencies. Poor status is also seen in affluent countries such as in Norway. Vitamin B12 is crucial for normal cell division and differentiation and necessary for the development and myelination of the central nervous system. Deficiency is also associated with impaired fetal and infant growth. In the proposed study we will measure the effect of daily oral vitamin B12 supplementation infants on neurodevelopment. We also aim to measure the impact of B12 supplementation on several other outcomes.

Study design: Individually randomized double-blind placebo-controlled trial breastfed infants who will be assigned to a screening group (in which measurements will be obtained immediately) or a control group (in which serum will be stored and measurements done after one year).

Pregnant women will be informed about the study during their first antenatal visit at the clinic and that we will re-approach them on their 6-week visit to their public health nurse. Infants who are deficient will be treated with peroral or intramuscular injections with 400 µg cyano-cobalamin.

Infants in the control group will not be offered any intervention their blood sample will be stored for one year and then analyzed for the same nutrients as the intervention group.

Outcomes: Primary: (i) neurodevelopment in children measured at 12 months of age (ii) growth in children measured by attained weight and length at 12 months. Secondary: (i) neurodevelopment and cognitive functioning in children later in life

Detailed Description

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Conditions

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Vitamin B 12 Deficiency

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Screening - treatment

From 6 weeks of age, infants will be screened for elevated plasma total homocysteine concentrations. Those who have a concentration above the defined cut-off will be treated with cobalamin (vitamin B12).

Group Type EXPERIMENTAL

Cyanocobalamin

Intervention Type BIOLOGICAL

Intramuscular injection of 400 µg cobalamin to children with elevated thcy at enrollment

Control

The control-group sample will be stored and analyzed when the child is 12 months old. Those with elevated tHcy will contribute to the control group.

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Cyanocobalamin

Intramuscular injection of 400 µg cobalamin to children with elevated thcy at enrollment

Intervention Type BIOLOGICAL

Other Intervention Names

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Vitamin B12

Eligibility Criteria

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Inclusion Criteria

1. Availability of informed verbal consent
2. Plan to reside in the defined study area for the next 12 months
3. Mothers intend to breastfeed their children for at least 8 months, and exclusively for 4 months

Exclusion Criteria

1. Severe systemic illness requiring hospitalization
2. Growth retardation
3. Severe congenital malformations
4. Plasma cobalamin concentration \<148 pmol/L (These children will be treated for vitamin B12 deficiency and not included in the RCT, but will be included in the cohort design)
Minimum Eligible Age

1 Month

Maximum Eligible Age

2 Months

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bergen

OTHER

Sponsor Role collaborator

University of Oslo

OTHER

Sponsor Role collaborator

Inland Norway University of Applied Sciences

OTHER

Sponsor Role collaborator

Sykehuset Innlandet HF

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Tor A Strand, M.D. / Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Sykehuset Innlandet HF

Locations

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Innlandet Hospital Trust

Lillehammer, , Norway

Site Status RECRUITING

Countries

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Norway

Central Contacts

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Carolien Konijnenberg, Ph.D

Role: CONTACT

+47 61 28 74 94

Kjersti S Bakken, Ph.D.

Role: CONTACT

+47 957 81 349

Facility Contacts

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Kjersti S Bakken, phd

Role: primary

+4795781349

Tor A Strand, phd

Role: backup

+4790971086

References

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Hay G, Johnston C, Whitelaw A, Trygg K, Refsum H. Folate and cobalamin status in relation to breastfeeding and weaning in healthy infants. Am J Clin Nutr. 2008 Jul;88(1):105-14. doi: 10.1093/ajcn/88.1.105.

Reference Type BACKGROUND
PMID: 18614730 (View on PubMed)

Torsvik I, Ueland PM, Markestad T, Bjorke-Monsen AL. Cobalamin supplementation improves motor development and regurgitations in infants: results from a randomized intervention study. Am J Clin Nutr. 2013 Nov;98(5):1233-40. doi: 10.3945/ajcn.113.061549. Epub 2013 Sep 11.

Reference Type BACKGROUND
PMID: 24025626 (View on PubMed)

Dror DK, Allen LH. Effect of vitamin B12 deficiency on neurodevelopment in infants: current knowledge and possible mechanisms. Nutr Rev. 2008 May;66(5):250-5. doi: 10.1111/j.1753-4887.2008.00031.x.

Reference Type BACKGROUND
PMID: 18454811 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26098427 (View on PubMed)

Bjorke-Monsen AL. Is exclusive breastfeeding ensuring an optimal micronutrient status and psychomotor development in infants? Clin Biochem. 2014 Jun;47(9):714. doi: 10.1016/j.clinbiochem.2014.05.022. Epub 2014 May 17. No abstract available.

Reference Type BACKGROUND
PMID: 24845709 (View on PubMed)

Forssman L, Ashorn P, Ashorn U, Maleta K, Matchado A, Kortekangas E, Leppanen JM. Eye-tracking-based assessment of cognitive function in low-resource settings. Arch Dis Child. 2017 Apr;102(4):301-302. doi: 10.1136/archdischild-2016-310525. Epub 2016 Aug 22.

Reference Type BACKGROUND
PMID: 27551061 (View on PubMed)

Graziano P, Derefinko K. Cardiac vagal control and children's adaptive functioning: a meta-analysis. Biol Psychol. 2013 Sep;94(1):22-37. doi: 10.1016/j.biopsycho.2013.04.011. Epub 2013 May 4.

Reference Type BACKGROUND
PMID: 23648264 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 23283502 (View on PubMed)

Bjorkevoll SMG, O'Keeffe M, Konijnenberg C, Solvik BS, Sodal AF, Kaldenbach S, McCann A, Ueland PM, Kvestad I, Ersvaer E, Holten-Andersen MN, Bakken KS, Strand TA. Infant vitamin B12 status and its predictors - cross-sectional baseline results from an ongoing randomized controlled trial. Am J Clin Nutr. 2025 Sep;122(3):803-810. doi: 10.1016/j.ajcnut.2025.06.029. Epub 2025 Jul 1.

Reference Type DERIVED
PMID: 40609749 (View on PubMed)

Bakken KS, Kvestad I, Bjorkevoll SMG, Solvik BS, Kaldenbach S, McCann A, Holten-Andersen MN, Ersvaer E, Konijnenberg C, Strand TA. Vitamin B12 status in infancy and the effect of a vitamin B12 injection in infants with subclinical vitamin B12 deficiency: study protocol for a register-based randomised controlled trial. BMJ Open. 2023 Apr 20;13(4):e069102. doi: 10.1136/bmjopen-2022-069102.

Reference Type DERIVED
PMID: 37080624 (View on PubMed)

Other Identifiers

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U1111-1267-0112

Identifier Type: OTHER

Identifier Source: secondary_id

9305-150426

Identifier Type: -

Identifier Source: org_study_id

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