Evaluation of Vitamin D Requirements During Pregnancy

• ClinicalTrials.gov Identifier: NCT00292591
• Recruitment Status: Completed
• First Posted: February 16, 2006
• Results First Posted: August 9, 2016
• Last Update Posted: September 19, 2016
• Sponsor: Medical University of South Carolina
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Carol Wagner, Medical University of South Carolina

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Vitamin D Deficiency	Drug: cholecalciferol (vitamin D3); Drug: cholecalciferol	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 501 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Prevention
• Official Title: Evaluation of Vitamin D Requirements During Pregnancy
• Study Start Date: January 2004
• Actual Primary Completion Date: January 2010
• Actual Study Completion Date: January 2010

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: cholecalciferol-400 IU; Control group receiving 400 IU/day plus 0 IU vitamin D3 as placebo/day	Drug: cholecalciferol (vitamin D3); randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day; Drug: cholecalciferol; comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy; Other Name: vitamin D3
Experimental: cholecalciferol 2000 IU; Experimental group receiving 2000 IU total vitamin D3/day.	Drug: cholecalciferol (vitamin D3); randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day; Drug: cholecalciferol; comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy; Other Name: vitamin D3
Experimental: cholecalciferol 4000 IU; Experimental group receiving 4000 IU/day cholecalciferol	Drug: cholecalciferol (vitamin D3); randomized control trial of three vitamin D doses: 400, 2000 and 4000 IU/day; Drug: cholecalciferol; comparing vitamin D requirements of pregnant women and their fetuses from 12 weeks' gestation through pregnancy; Other Name: vitamin D3

Outcome Measures

Primary Outcome Measures :

1. 25-Hydroxyvitamin D Concentration [ Time Frame: 7 months ]
   Circulating total 25(OH)D concentration measured in serum at visit 7, one month prior to delivery

Eligibility Criteria

• Ages Eligible for Study: 16 Years to 45 Years (Child, Adult)
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

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.)

Contacts and Locations

Locations

United States, South Carolina

Medical University of South Carolina

Charleston, South Carolina, United States, 29425

Sponsors and Collaborators

Medical University of South Carolina

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

Investigators

• Principal Investigator: Bruce W. Hollis, Ph.D.; Medical University of South Carolina
• Principal Investigator: Carol L. Wagner, M.D.; Medical University of South Carolina
• Study Director: Donna Johnson, M.D.; Medical University of South Carolina
• Study Chair: Thomas C. Hulsey, Sc.D.; Medical University of South Carolina

More Information

Publications of Results:

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. Erratum in: J Bone Miner Res. 2011 Dec; 26(12):3001.

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. Review.

Other Publications:

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. Review.

Hollis BW, Wagner CL. Normal serum vitamin D levels. N Engl J Med. 2005 Feb 3;352(5):515-6; author reply 515-6.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Carol Wagner, Professor of Pediatrics, Medical University of South Carolina
• ClinicalTrials.gov Identifier: NCT00292591
• Other Study ID Numbers: R01HD043921 ( U.S. NIH Grant/Contract ); 5R01HD043921 ( U.S. NIH Grant/Contract )
• First Posted: February 16, 2006
• Results First Posted: August 9, 2016
• Last Update Posted: September 19, 2016
• Last Verified: August 2016

Keywords provided by Carol Wagner, Medical University of South Carolina:

vitamin D; cholecalciferol; pregnancy; bone mineral density

Additional relevant MeSH terms:

Vitamin D Deficiency; Vitamin D; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Ergocalciferols; Cholecalciferol; Vitamins; Micronutrients; Physiological Effects of Drugs; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents