Early Infant Micronutrition and Development (RART)
Primary Purpose
Vitamin B 12 Deficiency
Status
Recruiting
Phase
Phase 2
Locations
Norway
Study Type
Interventional
Intervention
Cyanocobalamin
Sponsored by
About this trial
This is an interventional treatment trial for Vitamin B 12 Deficiency focused on measuring Nutrition, Vitamins, Breastfeeding, Infant, Neurodevelopment, Growth, Clinical trial
Eligibility Criteria
Inclusion Criteria:
- Availability of informed verbal consent
- Plan to reside in the defined study area for the next 12 months
- Mothers intend to breastfeed their children for at least 8 months, and exclusively for 4 months
Exclusion Criteria:
- Severe systemic illness requiring hospitalization
- Growth retardation
- Severe congenital malformations
- 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)
Sites / Locations
- Innlandet Hospital TrustRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
No Intervention
Arm Label
Screening - treatment
Control
Arm Description
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).
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.
Outcomes
Primary Outcome Measures
Neurodevelopment
Bayley Scales of Infant Development 4th edition
Prevalence of vitamin B12 deficiency
Number of children with elevated plasma homocysteine or low cobalamin
Prevalence of other vitamin deficiencies
Number of infants with vitamin deficiencies other than vitamin B12 deficiency
Secondary Outcome Measures
Neurodevelopment measured by the Ages and Stages Questionaire
Ages and Stages Questionnaire version 3 repeated throughout infancy
Vagal tone
Heart rate variability
Eye tracking
Visual acuity, visuospatial orientation, and attention to social cues
Neurodevelopment later in childhood
General cognitive abilities ("IQ") assessed by the Wechsler Preschool and Primary Scale of Intelligence
Adverse events
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Full Information
NCT ID
NCT05005897
First Posted
August 9, 2021
Last Updated
April 14, 2023
Sponsor
Sykehuset Innlandet HF
Collaborators
University of Bergen, University of Oslo, Inland Norway University of Applied Sciences
1. Study Identification
Unique Protocol Identification Number
NCT05005897
Brief Title
Early Infant Micronutrition and Development
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 8, 2021 (Actual)
Primary Completion Date
October 15, 2025 (Anticipated)
Study Completion Date
October 15, 2029 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sykehuset Innlandet HF
Collaborators
University of Bergen, University of Oslo, Inland Norway University of Applied Sciences
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief 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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Vitamin B 12 Deficiency
Keywords
Nutrition, Vitamins, Breastfeeding, Infant, Neurodevelopment, Growth, Clinical trial
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
600 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Screening - treatment
Arm Type
Experimental
Arm Description
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).
Arm Title
Control
Arm Type
No Intervention
Arm Description
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.
Intervention Type
Biological
Intervention Name(s)
Cyanocobalamin
Other Intervention Name(s)
Vitamin B12
Intervention Description
Intramuscular injection of 400 µg cobalamin to children with elevated thcy at enrollment
Primary Outcome Measure Information:
Title
Neurodevelopment
Description
Bayley Scales of Infant Development 4th edition
Time Frame
12 months of age
Title
Prevalence of vitamin B12 deficiency
Description
Number of children with elevated plasma homocysteine or low cobalamin
Time Frame
1-3 months of age
Title
Prevalence of other vitamin deficiencies
Description
Number of infants with vitamin deficiencies other than vitamin B12 deficiency
Time Frame
1-3 months of age
Secondary Outcome Measure Information:
Title
Neurodevelopment measured by the Ages and Stages Questionaire
Description
Ages and Stages Questionnaire version 3 repeated throughout infancy
Time Frame
4-12 months of age
Title
Vagal tone
Description
Heart rate variability
Time Frame
12 months of age
Title
Eye tracking
Description
Visual acuity, visuospatial orientation, and attention to social cues
Time Frame
12 months of age
Title
Neurodevelopment later in childhood
Description
General cognitive abilities ("IQ") assessed by the Wechsler Preschool and Primary Scale of Intelligence
Time Frame
5 years
Title
Adverse events
Description
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
Time Frame
3 months after treatment with vitamin B12
Other Pre-specified Outcome Measures:
Title
Thyroid function
Description
Infant thyroid function measured by the concentration of the hormones TSH, T3, and T4
Time Frame
12 months of age
10. Eligibility
Sex
All
Minimum Age & Unit of Time
1 Month
Maximum Age & Unit of Time
2 Months
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Availability of informed verbal consent
Plan to reside in the defined study area for the next 12 months
Mothers intend to breastfeed their children for at least 8 months, and exclusively for 4 months
Exclusion Criteria:
Severe systemic illness requiring hospitalization
Growth retardation
Severe congenital malformations
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)
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Carolien Konijnenberg, Ph.D
Phone
+47 61 28 74 94
Email
carolien.konijnenberg@inn.no
First Name & Middle Initial & Last Name or Official Title & Degree
Kjersti S Bakken, Ph.D.
Phone
+47 957 81 349
Email
Kjersti.Sletten.Bakken@sykehuset-innlandet.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tor A Strand, M.D. / Ph.D.
Organizational Affiliation
Sykehuset Innlandet HF
Official's Role
Principal Investigator
Facility Information:
Facility Name
Innlandet Hospital Trust
City
Lillehammer
ZIP/Postal Code
2615
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kjersti S Bakken, phd
Phone
+4795781349
Email
kjerstisbakken@gmail.com
First Name & Middle Initial & Last Name & Degree
Tor A Strand, phd
Phone
+4790971086
Email
tors@me.com
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
We plan to share data with other researchers.
IPD Sharing Time Frame
Data will be available not later than 5 years after the study have completed enrollment and the first year of follow-up of all children.
IPD Sharing Access Criteria
Data available on request. In order to meet ethical requirements for the use of confidential patient data, requests must be approved by Regional Committee for Medical and Health Research Ethics in Norway.
Citations:
PubMed Identifier
18614730
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.
Results Reference
background
PubMed Identifier
24025626
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.
Results Reference
background
PubMed Identifier
18454811
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.
Results Reference
background
PubMed Identifier
26098427
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.
Results Reference
background
PubMed Identifier
24845709
Citation
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.
Results Reference
background
PubMed Identifier
27551061
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.
Results Reference
background
PubMed Identifier
23648264
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.
Results Reference
background
PubMed Identifier
23283502
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.
Results Reference
background
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Early Infant Micronutrition and Development
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