Study Comparing Two Isoforms of Vitamin D Supplements for Infants
Information source: McGill University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Healthy
Intervention: Cholecalciferol (D3) or ergocalciferol (D2) (Dietary Supplement)
Phase: Phase 3
Status: Completed
Sponsored by: McGill University Official(s) and/or principal investigator(s): Hope A, Weiler, PhD, RD, Principal Investigator, Affiliation: McGill University Celia Rodd, MD, Principal Investigator, Affiliation: Montreal Children's Hospital, McGill University Health Center Sina Gallo, MSc, RD, Principal Investigator, Affiliation: McGill University
Summary
There are two different types of vitamin D - vitamin D3 (animal source) and vitamin D2
(plant source). Almost all the usual vitamin D preparations for infants available in
Canadian pharmacies contain vitamin D3 which may not be suitable for families who avoid
animal products for social or religious reasons. The purpose of this study is to learn more
about the two forms of vitamin D and if blood levels of vitamin D are similar in infants
after taking them. Forty-eight breastfed infants will be randomly assigned to 400 IU of
either vitamin D2 or D3 supplement for 3 months starting at 1 month of age. The difference
in blood vitamin D levels, after 3 months of supplementation, between the two groups will
help determine if the two supplements are equal.
Clinical Details
Official title: Bio-equivalency Study of the Effects of Vitamin D2 and Vitamin D3 Supplements on 25-hydroxyvitamin D Levels in Exclusively Breast Fed Canadian Infants
Study design: Allocation: Randomized, Endpoint Classification: Bio-equivalence Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: Equivalency of isoforms
Detailed description:
Vitamin D is important to develop strong bones and teeth as well as to prevent rickets, a
childhood bone disease in which the bones get very soft and bend. the investigators know
that vitamin D can be produced by cells in our skin during sunny months of the year but
there is a concern about the safety of sun exposure in infants. As well breast milk contains
very little vitamin D. It is for this reason that Health Canada recommends all breast fed
babies should receive 400 IU of vitamin D per day. There are two different types of vitamin
D - vitamin D3 (animal source) and vitamin D2 (plant source). Standard infant preparations
in Canada tend to be in the vitamin D3 form. To date, there is insufficient information to
judge the equivalency of 400 IU of vitamin D2 and D3 given daily in very young Canadian
infants. In view of over 1 million Canadian families practicing vegetarianism, this would
appear to be an important and not yet answered question. The investigators cannot
extrapolate from the adult data because the infant physiology is immature relative to adults
and absorption, especially of fat soluble vitamins differs. This area needs to be better
evaluated to emphasize the optimal isoform of vitamin D during infancy necessary for the
development of adequate bone mass.
This study aims to compare the relative ability of equal daily intakes of vitamin D2 and D3,
amounts (400 IU/d) currently recommended by Health Canada, to support circulating 25(OH)D
concentrations after 3 months of supplementation in breastfed newborns. In particular,
whether both supplements are equally effective in their ability to achieve and sustain
optimal plasma 25(OH)D concentrations, defined as 25(OH)D values between 75-225 nmol/L.
Design: Randomized clinical trial in which 48, 1 month old infants, will be randomized to
either the vitamin D2 or D3 isoform at the standard of care dosage (400 IU daily) for 3
months; a sufficient time to observe a change of vitamin D status ascribed to the
supplement. Infant physiology is immature and evolving and the time to stabilize 25-hydroxy
vitamin D (25(OH)D) is approximately 3 weeks (half-life). Supplements will be double blinded
to participants, investigators and all staff.
Recruitment: Infants will be recruited from 1 large primary care center located in the
greater Montreal area. The goal is for infants to begin the study at 4 weeks of age but a
range of +/- 2 weeks. Rolling recruitment over a 9 months period with a 3 month follow-up
for all beginning in May 2010. This covers both the synthesizing and non synthesizing
periods of vitamin D. This age group has been selected (first month of life) since vitamin
D stores transferred from the mother begin to decrease owing to the 15 to 30 day half life
of 25(OH)D. After this point, infants need a source of vitamin D other than breast milk or
sunshine. Because the majority of Canadian infants are now breastfed for at least 3-6 months
of age the first 4 months of life appear to be an important time frame to examine the
relative potency of the 2 isoforms.
Frequency and duration of follow up: Infants will be followed for 3 months with 2 visits, at
baseline (~1 month) and the end of the study (~4 months). Visits will include anthropometric
assessment and blood collection for the assessment of 25(OH)D and parathyroid hormone (PTH)
concentrations. Bottles of supplement will be weighed upon receipt and return for
compliance. As well, parents will be asked to self-report compliance at each visit. In
order to encourage continued supplementation during the 3 month intervention, the
investigators plan to a schedule a reminder phone call at approximately 1½ months post the
baseline visit. Vitamin D supplementation of infants prior to the initial visit (birth to
visit 1) will be documented, but considered as systematic error. Maternal baseline
information will be collected at the first visit including demographics, ethnicity,
pregnancy history and sun exposure during pregnancy. This data will be used to characterize
the study population. At each visit, the health status and sun exposure and sunscreen use of
the infants will be assessed. A computerized narrow band reflectometer will be utilized to
measure skin pigmentation on unexposed skin of the inner upper arm and forehead. Procedures
will be performed using guidelines established by the European Society of Contact
Dermatitis. This test estimates melanin content of the skin which influences vitamin D
status.
Sample procurement: At both visits, blood will be collected from infants using a capillary
blood sample and from mothers by venipuncture. All samples will be taken between 8 and 10 am
to control for diurnal variation. Approximately 1 ml of heparinized blood will be collected
from infants via heel/finger prick and 5 ml from mothers.
Plasma 25(OH)D and PTH concentrations: Response to supplementation will be evaluated by the
change in plasma 25(OH)D and PTH. Mothers 25(OH)D status will also be obtained to determine
that both groups are similar as mother's vitamin D status can affect infant's vitamin stores
and risk of hypovitaminosis. Mother's vitamin D status will also allow us to better
establish total infant vitamin D exposure through maternal placental transfer of vitamin D.
If there is no change, the proportion with 25(OH)D below target will be examined. Both
vitamin D and PTH will be measured using an automated chemiluminescent assay system
(Liaison, Diasorin). All analyses will be completed in a laboratory meeting the performance
targets set by the Vitamin D External Quality Assessment Scheme (DEQAS).
Anthropometry: Infant's weight, length and head circumference will be taken at each visit.
Gestational age will be documented from the vaccination booklet. Growth will be assessed
using triplicate measurements of weight (to nearest g without clothing/diaper using a
digital infant scale) and head circumference (to the nearest 0. 1 cm using non-stretchable
tape). Data will be expressed in absolute units and z-scores using data from the World
Health Organization growth charts at each age. Mother's weight, height and body composition
(% body fat using bioelectrical impendence will be measured to accurately describe the
population.
Infant nutrition: Information of infant feeding status (exclusively, predominately breastfed
or formula fed) will be collected at each visit as well as the reminder telephone call
(approximately 1½ most post supplementation). If formula is consumed, information about
specific amounts consumed, frequency, brands as well as additional multivitamins/minerals
will also be collected.
Mother's nutrition: Mother's vitamin D intake from diet and supplements will be assessed
during lactation using a 24 hour recall, using the US Department of Agriculture 5-step
multiple-pass method for dietary recall, conducted with a registered dietitian at each
visit. The correct assessment of 25(OH)D from dietary food records is limited as current
food sources of vitamin D (such as fish) are consumed weekly or a few times/month. 24-hours
recalls will likely miss important food sources thus, the Canadian adapted Harvard Food
Frequency Questionnaire will be completed to assess last 3 months of usual food intake.
Safety: Participants found to be below the optimal range of vitamin D [25(OH)D ≤ 75 nmol/L,
30 ng/ml] or any value exceeding 225 nmol/L [90 ng/ml] after the 3-month supplementation
period, upon participant consent, will be contacted and referred to their pediatrician for
appropriate treatment. If permitted by the participant, the physician will be contacted
directly with the results. Both maternal and infant 25(OH)D values collected at the visit 2
will be made available to all participants.
Eligibility
Minimum age: N/A.
Maximum age: 6 Weeks.
Gender(s): Both.
Criteria:
Inclusion Criteria:
- Healthy, singleton term infants of appropriate for gestational age, according to
Centers for Disease Control (CDC) growth charts based on weight at birth between 5th
and 95th percentiles for sex
- Born to healthy breastfeeding women
- Exclusively breast fed infants from birth, according to WHO definition: breast milk,
expressed breast milk, vitamins, minerals and medicine but not including water,
breast milk substitutes, other liquids and solid foods.
Exclusion Criteria:
- Infants of mothers with a history of gestational diabetes or hypertension in
pregnancy; chronic alcohol use; malabsorption syndromes (Celiac disease, Crohn's,
etc.), due to malabsorption of fat soluble vitamins
- Mothers taking any medications that can affect vitamin D metabolism (anticonvulsants
and corticosteroids)
- Mothers taking ≥ 2,000 IU/d of vitamin D from supplementation
Locations and Contacts
Mary Emily Clinical Nutrition Research Unit, Ste. Anne de Bellevue, Quebec H9X 3V9, Canada
Additional Information
Study website
Starting date: March 2010
Last updated: March 1, 2012
|