Evaluation of Vitamin D Requirements During Pregnancy

NCT ID: NCT00292591

Last Updated: 2016-09-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 501 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-01-31
• Study Completion Date: 2010-01-31

Brief Summary

The purpose of this study is to determine the effectiveness of vitamin D supplementation during pregnancy starting at the beginning of the second trimester. Mothers will be randomized to one of three vitamin D dosing groups: 400, 2,000 or 4,000 international units per day. It is hypothesized that the highest dosing regimen will result in a better vitamin D status of women regardless of their ethnicity or race.

Detailed Description

The prevalence of hypovitaminosis D in reproductive aged African-American women occurs at a rate of > 40%. Two factors have contributed to this public health problem: an inadequate DRI for vitamin D and avoidance of sun exposure/use of sunscreen. This startling rate of hypovitaminosis D requires that the DRI for vitamin D in pregnancy be evaluated in a detailed manner. The Cochrane Library (2002) released a report stating that there is insufficient data to evaluate the effects of vitamin D supplementation during pregnancy. Recently, the safety of prolonged supplementation with up to 25x's DRI (10,000 IU/day) was demonstrated in nonpregnant adults. It is essential to determine what dose of vitamin D is required to eliminate hypovitaminosis D during pregnancy and provide the fetus/neonate with adequate vitamin D stores during development and growth, particularly in darkly pigmented individuals. The aim of this research proposal, then, is to determine the efficacy, effectiveness, and safety of maternal vitamin D supplementation (as a function of ethnicity and UV exposure) in the prevention of hypovitaminosis D in the pregnant mother and her fetus/neonate. We hypothesize that darkly pigmented mothers will require substantially higher oral supplementation with vitamin D to eliminate hypovitaminosis D as compared to their Caucasian counterparts. We propose a comprehensive clinical trial to test our hypothesis. Mothers at 12 weeks' gestation will be randomized to one of three vitamin D treatment groups:

1. Control, 400-,

2. 2,000-, or

3. 4,000 IU/day to be continued throughout pregnancy.

Calcium and vitamin D homeostasis and skeletal remodeling in the mother will be monitored closely throughout the pregnancy. Bone density of the mother will be measured at 12 weeks' gestation and one-month postpartum. Follow-up growth and skeletal integrity assessments of the infant will be performed at birth, 1, 6 and 12 months stratified by infant feeding regime. Through these proposed studies, the prevalence of hypovitaminosis D among mothers, their developing fetuses and neonates, and the utility of maternal therapeutic intervention with vitamin D for both mother and fetus/infant will be assessed.

Conditions

Vitamin D Deficiency

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

cholecalciferol-400 IU

Control group receiving 400 IU/day plus 0 IU vitamin D3 as placebo/day

Group Type: ACTIVE_COMPARATOR

cholecalciferol (vitamin D3)

Intervention Type: DRUG

randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day

cholecalciferol

Intervention Type: DRUG

comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy

cholecalciferol 2000 IU

Experimental group receiving 2000 IU total vitamin D3/day.

Group Type: EXPERIMENTAL

cholecalciferol (vitamin D3)

Intervention Type: DRUG

randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day

cholecalciferol

Intervention Type: DRUG

comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy

cholecalciferol 4000 IU

Experimental group receiving 4000 IU/day cholecalciferol

Group Type: EXPERIMENTAL

cholecalciferol (vitamin D3)

Intervention Type: DRUG

randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day

cholecalciferol

Intervention Type: DRUG

comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy

Interventions

cholecalciferol (vitamin D3)

randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day

Intervention Type: DRUG

cholecalciferol

comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy

Intervention Type: DRUG

Other Intervention Names

vitamin D3

Eligibility Criteria

Inclusion Criteria

1. Women who are within the ages of 16-45 years

2. In good general health

3. Less than 12 weeks pregnant (based on last menstrual period)

Exclusion Criteria

1. Mothers with preexisting type I or type II diabetes

2. Mothers with preexisting hypertension

3. Mothers with preexisting parathyroid disease or uncontrolled thyroid disease

4. Mothers with multiple fetuses (e.g., twins, triplets, etc.)

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Carol Wagner

Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bruce W. Hollis, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Carol L. Wagner, M.D.

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Donna Johnson, M.D.

Role: STUDY_DIRECTOR

Medical University of South Carolina

Thomas C. Hulsey, Sc.D.

Role: STUDY_CHAIR

Medical University of South Carolina

Locations

Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

Hollis BW. Circulating 25-hydroxyvitamin D levels indicative of vitamin D sufficiency: implications for establishing a new effective dietary intake recommendation for vitamin D. J Nutr. 2005 Feb;135(2):317-22. doi: 10.1093/jn/135.2.317.

Reference Type: BACKGROUND

PMID: 15671234 (View on PubMed)

Hollis BW, Wagner CL. Normal serum vitamin D levels. N Engl J Med. 2005 Feb 3;352(5):515-6; author reply 515-6. doi: 10.1056/NEJM200502033520521. No abstract available.

Reference Type: BACKGROUND

PMID: 15689596 (View on PubMed)

Hollis BW, Johnson D, Hulsey TC, Ebeling M, Wagner CL. Vitamin D supplementation during pregnancy: double-blind, randomized clinical trial of safety and effectiveness. J Bone Miner Res. 2011 Oct;26(10):2341-57. doi: 10.1002/jbmr.463.

Reference Type: RESULT

PMID: 21706518 (View on PubMed)

Hollis BW, Wagner CL. Vitamin D requirements and supplementation during pregnancy. Curr Opin Endocrinol Diabetes Obes. 2011 Dec;18(6):371-5. doi: 10.1097/MED.0b013e32834b0040.

Reference Type: RESULT

PMID: 21857221 (View on PubMed)

Palacios C, Kostiuk LL, Cuthbert A, Weeks J. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2024 Jul 30;7(7):CD008873. doi: 10.1002/14651858.CD008873.pub5.

Reference Type: DERIVED

PMID: 39077939 (View on PubMed)

Wei W, Shary JR, Garrett-Mayer E, Anderson B, Forestieri NE, Hollis BW, Wagner CL. Bone mineral density during pregnancy in women participating in a randomized controlled trial of vitamin D supplementation. Am J Clin Nutr. 2017 Dec;106(6):1422-1430. doi: 10.3945/ajcn.116.140459. Epub 2017 Oct 18.

Reference Type: DERIVED

PMID: 29046301 (View on PubMed)

Other Identifiers

5R01HD043921

Identifier Type: NIH

Identifier Source: secondary_id

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R01HD043921

Identifier Type: NIH

Identifier Source: org_study_id

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