Early Infant Micronutrition and Development

Vitamin B 12 Deficiency Clinical Trial

— RART  

Official title:

Vitamin B12 Status in Infancy and the Effect of Providing Vitamin B12 to Infants With Signs of Suboptimal Vitamin B12 Status - a Registry-based, Randomized Controlled Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05005897
• Other study ID #: 9305-150426
• Secondary ID: U1111-1267-0112
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 8, 2021
• Est. completion date: October 15, 2029

Study information

• Verified date: April 2023
• Source: Sykehuset Innlandet HF
• Contact: Carolien Konijnenberg, Ph.D
• Phone: +47 61 28 74 94
• Email: carolien.konijnenberg[@]inn.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 600
• Est. completion date: October 15, 2029
• Est. primary completion date: October 15, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Month to 2 Months

Eligibility

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)

Related Conditions & MeSH terms

• Vitamin B 12 Deficiency

Intervention

Biological:
• Cyanocobalamin
Intramuscular injection of 400 µg cobalamin to children with elevated thcy at enrollment

Locations

Country	Name	City	State
Norway	Innlandet Hospital Trust	Lillehammer

Sponsors (4)

Lead Sponsor	Collaborator
Sykehuset Innlandet HF	Inland Norway University of Applied Sciences, University of Bergen, University of Oslo

Country where clinical trial is conducted

Norway, 

References & Publications (8)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Thyroid function	Infant thyroid function measured by the concentration of the hormones TSH, T3, and T4	12 months of age
Primary	Neurodevelopment	Bayley Scales of Infant Development 4th edition	12 months of age
Primary	Prevalence of vitamin B12 deficiency	Number of children with elevated plasma homocysteine or low cobalamin	1-3 months of age
Primary	Prevalence of other vitamin deficiencies	Number of infants with vitamin deficiencies other than vitamin B12 deficiency	1-3 months of age
Secondary	Neurodevelopment measured by the Ages and Stages Questionaire	Ages and Stages Questionnaire version 3 repeated throughout infancy	4-12 months of age
Secondary	Vagal tone	Heart rate variability	12 months of age
Secondary	Eye tracking	Visual acuity, visuospatial orientation, and attention to social cues	12 months of age
Secondary	Neurodevelopment later in childhood	General cognitive abilities ("IQ") assessed by the Wechsler Preschool and Primary Scale of Intelligence	5 years
Secondary	Adverse events	Number of participants with treatment-related adverse events as assessed by CTCAE v4.0	3 months after treatment with vitamin B12