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Trial record 25 of 107 for:    ( Map: Nepal )

Vitamin B12 Supplementation During Pregnancy on Cognitive Development (VitaPreg)

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ClinicalTrials.gov Identifier: NCT03071666
Recruitment Status : Recruiting
First Posted : March 7, 2017
Last Update Posted : July 17, 2018
Sponsor:
Collaborators:
Tribhuvan University Teaching Hospital, Institute Of Medicine.
Uni Research
Sykehuset Innlandet HF
Information provided by (Responsible Party):
Centre For International Health

Brief Summary:

Scientific basis: Globally, vitamin B12 deficiency is one of the most common micronutrient deficiencies. The only relevant source of vitamin B12 is animal-source foods and poor gut function may decrease absorption. 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 to pregnant women on neurodevelopment and growth of their children. We also aim to measure the impact of B12 supplementation on several other outcomes.

Study design: Individually randomized double-blind placebo controlled trial in pregnant South Asian women at risk of poor vitamin B12 status. Participants will be randomized in a 1:1 ratio.

Study participants and site: 600 pregnant women from early pregnancy. Women will be enrolled as early as possible, but no later than in week 15 of pregnancy.

Intervention: Daily administration of 50 µg of vitamin B12 from early pregnancy until 6 months after birth.

Comparator: Placebo, identical to the vitamin B12 supplements.

Outcomes: Primary: (i) neurodevelopment in children measured at 6 and 12 months of age (ii) growth in children measured by weight and length at 12 months. Secondary: (i) neurodevelopment and cognitive functioning in children at 24 months (ii) gestational age at birth, (iii) fetal and infant growth measured by weight and length at birth, after 1 month and then at 3, 6, 9, and 24 months, (iv) hemoglobin concentration in children and mothers.

Relevance for programs and public health: The results from this study can suggest new dietary guidelines for South Asian women that again can lead to improved pregnancy outcomes and neurodevelopment and cognitive functioning in South Asian children.


Condition or disease Intervention/treatment Phase
Pregnancy Related Vitamin B 12 Deficiency Anemia Dietary Supplement: cobalamin Dietary Supplement: placebo Phase 2 Phase 3

Detailed Description:

Cobalamin (Vitamin B12) deficiency is common in many low- and middle-income countries. This is not surprising as the main source of vitamin B12 is animal source foods, which are expensive and for cultural and religious reasons often not eaten at all. We have in several studies in women and children demonstrated that poor vitamin B12 status is common in South Asia. There is also compelling evidence that vitamin B12 deficiency occurs frequently in many other settings including pregnant women .

Case studies have demonstrated harmful effects of severe vitamin B12 deficiency on the developing infant brain.The consequences of mild or subclinical vitamin deficiency are less clear but it has been shown to be associated with decreased cognitive performance in both elderly and children.

Three randomized controlled trials (RCT) have measured the effect of vitamin B12 supplementation on neurodevelopment in children: In a Norwegian trial, an intramuscular injection of B12 substantially improved motor development in six weeks old infants after one month. Another intervention study in low birth weight children in Norway recently confirmed these findings. The infants in these studies had evidence of suboptimal vitamin B12 status, but none were severely deficient. We found a beneficial effect of vitamin B12 supplementation for six months on neurodevelopment in young North Indian children.

During pregnancy, vitamin B12 is concentrated in the fetus and stored in the liver. Infants born to vitamin B12-replete mothers have stores of vitamin B12 that are adequate to sustain them for the first several months postpartum. Consequently, vitamin B12 deficiency rarely occurs before the infant is about four months old if the mother has adequate vitamin B12 status during pregnancy. However, many infants of vitamin B12-deficient breastfeeding mothers are vulnerable to B12 deficiency from an early age.

In this project we will randomise Nepalese women to receive a supplement containing 50µg cobalamin or a placebo from early pregnancy until 6 months postpartum.

Hypothesis to be tested

Principal hypothesis: Daily administration of vitamin B12 to pregnant women from early pregnancy until 6 months postpartum will:

  1. Increase the scores of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III) by 0.25 SD points measured at 6 and 12 months of age.
  2. Increase length for age and weight for length by 0.2 z-scores at 12 months of age.

Other hypotheses to be tested (dependent on additional funding):

  1. Daily maternal administration of vitamin B12 from the start of the early pregnancy and for 6 months postpartum improves the hemoglobin concentration in the mother and infant.
  2. Daily maternal administration of vitamin B12 from early pregnancy and for 6 months postpartum improves plasma vitamin B12 concentration and reduces plasma total homocysteine and methylmalonic acid concentration in the mother and infant.
  3. Daily maternal administration of vitamin B12 from early pregnancy and for 6 months postpartum improves insulin sensitivity in the offspring.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 600 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: We will randomize women in a 1:1 ratio. The vitamin B12 supplements and the placebos will be produced specifically for this trial and be identical in taste and appearance. Each woman will be assigned a packet of medicines according to her id number. This packet will only be labeled with general information about the study and a unique id number. The list that links the id number to the randomization code will be kept with the company that produces the intervention and the placebo, and with the scientist who will generate the randomization code. This scientist will otherwise not be involved in the study. None of the investigators will have access to this list until completion of data collection and cleaning of data for the main outcomes.
Primary Purpose: Prevention
Official Title: Supplementation of Vitamin B12 in Pregnancy and Postpartum on Growth and Cognitive Functioning in Early Childhood: A Randomized, Placebo Controlled Trial
Actual Study Start Date : March 27, 2017
Estimated Primary Completion Date : June 28, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: B Vitamins

Arm Intervention/treatment
Experimental: Vitamin B12
cobalamin, 50 µg per day throughout pregnancy and during the first 6 months postpartum.
Dietary Supplement: cobalamin
Vitamin supplment tablet containing 50µg cobalamin
Other Name: Vitamin B12

Placebo Comparator: Placebo
Identical taste and appearance with the Experimental arm. Contains no cobalamin
Dietary Supplement: placebo
A tablet identical to the vitamin supplement but containing no vitamin B12




Primary Outcome Measures :
  1. Length [ Time Frame: 12 first months of life ]
    Length measured in centimeters

  2. Neurodevelopment [ Time Frame: 12 first months of life ]
    Infant Scores of the Bayley Scales of Infant Development version 3

  3. Weight [ Time Frame: 12 first months of life ]
    Weight measured in kilograms


Secondary Outcome Measures :
  1. Child hemoglobin concentration [ Time Frame: 12 first months of life ]
    Hemoglobin measured by hemocue in full blood

  2. Child development [ Time Frame: 12 first months of life ]
    Infant scores of the Ages and Stages Questionnaire - 3rd ed.

  3. Heart rate variability [ Time Frame: 12 first months of life ]
    Heart rate variability or vagal tone

  4. Sleep and activity [ Time Frame: 12 first months of life ]
    Sleep and activity measured by Actigraph (Actiwatch)

  5. The Infant Motor Performance [ Time Frame: 2 months after birth ]
    Screening tool to assess motor development

  6. Still births [ Time Frame: Birth. ]
    Number of still births

  7. Maternal hemoglobin concentration [ Time Frame: Birth. ]
    Hemoglobin measured by hemocue in full blood

  8. Number of complicated births [ Time Frame: Birth. ]
    Number of births that were complicated

  9. Children born at small for gestational age [ Time Frame: Birth ]
    Number of children born at small for gestational age



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Ages Eligible for Study:   20 Years to 40 Years   (Adult)
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   The study target pregnant women.
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Pregnant mother in early pregnancy and not later than 15 weeks of pregnancy.
  • Current resident and plan to reside in Bhaktapur district for at least the next 2 years.
  • Age of mother between 18 and 40 years.
  • Consent to participate in the study.

Exclusion Criteria:

  • Taking or plan to take dietary or multivitamin supplements containing vitamin B12.
  • Known case of chronic disease like asthma, tuberculosis, diabetes, hypertension, hypo or hyperthyroidism or others
  • Known case of current high risk pregnancy
  • Severe anemia (hemoglobin concentration <7 g/dL).
  • Where the study doctor finds it necessary to treat the woman with vitamin B12 or vitamin B12 containing supplements

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 ClinicalTrials.gov identifier (NCT number): NCT03071666


Contacts
Contact: Laxman Shrestha, MD +977985036550 laxmanshree12@gmail.com
Contact: Sudha Basnet, MD/PhD +977 9841209799 sudhacbasnet@gmail.com

Locations
Nepal
Manjeswori Ulak Recruiting
Bhaktapur, Nepal, P.O.Box 40
Contact: Manjeswori Ulak, MD/MPhil    6612945    manjeswori@gmail.com   
Contact: Shyam S Dhaubhadel       founder@smf.org.np   
Sub-Investigator: Merina Shrestha, MD         
Principal Investigator: Ram K Chandyo, MD PhD         
Principal Investigator: Laxman Shrestha, MD Professor         
Sponsors and Collaborators
Centre For International Health
Tribhuvan University Teaching Hospital, Institute Of Medicine.
Uni Research
Sykehuset Innlandet HF
Investigators
Principal Investigator: Tor A Strand, MD/PhD University of Bergen
Principal Investigator: Laxman Shestha, MD Tribhuvan University
Principal Investigator: Ram K Chandyo, MD/PhD Kathmandu University

Additional Information:
Publications:

Responsible Party: Centre For International Health
ClinicalTrials.gov Identifier: NCT03071666     History of Changes
Other Study ID Numbers: CISMAC-B12
Universal Trial Number ( Registry Identifier: U1111-1183-4093 )
First Posted: March 7, 2017    Key Record Dates
Last Update Posted: July 17, 2018
Last Verified: July 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Individual participant data will be shared with other researchers upon request after completion of the study (data collection) and after publication of the main outcomes. And if the ethical review boards approve the use of the data for other purposes that what is described in the proposal.

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Centre For International Health:
Nepal
South Asia
Nutrition
Pregnancy
Neurodevelopment
Growth

Additional relevant MeSH terms:
Vitamin B 12 Deficiency
Vitamin B Deficiency
Avitaminosis
Deficiency Diseases
Malnutrition
Nutrition Disorders
Vitamins
Vitamin B 12
Hydroxocobalamin
Vitamin B Complex
Micronutrients
Growth Substances
Physiological Effects of Drugs
Hematinics