Vitamin D Supplementation in Younger Women (VITADAS)

Optimum Vitamin D Nutrition in Young Women

That on average it will require a vitamin D dose of 1700IU/day to increase the serum 25hydroxyvitamin D level from 20 to 30ng/ml in young Caucasian women and a dose of 1860 to 2480 IU/day in African American

Study Overview

• Status: Completed
• Conditions: Hypovitaminosis D
• Intervention / Treatment: Dietary supplement: vitamin D3

Detailed Description

Vitamin D is a unique nutrient in that its requirement can be met by both endogenous production from sun and from diet, which makes it difficult to determine the actual requirements as for other nutrients. The current recommended dietary reference intake (DRI) for vitamin D is 200 IU for adults between 25- 50 years, 400 IU for adults between 51-70 years and 600 IU for adults 70 years of age. In view of many scientists in the field of vitamin D, the current DRI of vitamin D is too low. This is mainly because of the increase in prevalence of vitamin D deficiency observed in the population based on measured serum 25OHD levels. It is now recognized that serum 25OHD is an indicator of vitamin D status. There is a growing consensus that serum 25OHD concentration of at least 30-32 ng/ml are needed to reduce serum Parathyroid hormone (PTH) and reduce bone loss. Also, research over the last two decades has provided additional evidence that higher vitamin D levels (25OHD 30ng/ml) are necessary for optimum overall health and prevent disease. There is no clear view of the amount of vitamin D intake required to maintain the optimum level of serum 25OHD levels in the population of all ages and there are no systematic dose response studies of vitamin D in women of all ages. A few studies carried out with different sexes and age groups have suggested that an untreated subject with a serum 25OHD concentration of 20 ng/ml would need a daily dose of ~1700 IU/d of Vitamin D3 to reach a serum 25OHD of 32 ng/ml in Caucasians, while in African Americans the Vitamin D3 requirement would be higher - 1860-2480 IU/d.

The current proposal aims at studying the dose response effect of vitamin D3 400 IU, 800 IU,1600 IU and 2400 IU or placebo on serum 25OHD and serum PTH in young women with vitamin D insufficiency (serum 25OHD <20 ng/ml) and an adequate calcium intake of 1000mg/day.

Another aim of the study is to establish the minimum effective dose of vitamin D3 which Normalizes PTH in Caucasian and African American young women. Vitamin D dose that reduces serum PTH to normal level in 97% of normal population is the recommended dietary allowance.

We will also establish the safety of these higher doses of vitamin D supplementation relating to hypercalcemia/hypercalcuria.

• Study Type: Interventional
• Enrollment (Actual): 198
• Phase: Not Applicable

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Premenopausal women, minimum age 25 years, maximum age 45 years. (Women with hysterectomy and/or oophorectomy must have a premenopausal FSH level.)
2. Serum 25OHD level: 5 - 20 ng/ml
3. BMI < 45 kg/m2.
4. Willing to discontinue vitamin D supplements after entering the study.
5. Negative pregnancy test before BMD and calcium absorption tests.
6. Willing to give signed informed consent form
7. Subject is Caucasian or African American

Exclusion Criteria:

1. Cancer (exceptions: basal cell carcinoma or if cancer occurred more than 10 years ago) or terminal illness.
2. Previous hip fracture.
3. Hemiplegia.
4. Uncontrolled type I diabetes ± significant proteinuria or fasting blood sugar >140 mg in type II diabetes.
5. Kidney stones- > 2 in a lifetime.
6. Chronic renal failure (serum creatinine >1.4 mg/dl).
7. Evidence of chronic liver disease, including alcoholism.
8. Physical conditions such as severe osteoarthritis, rheumatoid arthritis, heart failure severe enough to prevent reasonable physical activity.
9. Previous treatment with bisphosphonates (more that 3 months), PTH or PTH derivatives, (e.g. Teriparatide) or Fluoride in the last 6 months.
10. Previous treatment within the last 6 months with calcitonin or estrogen (except birth control pills).
11. Chronic high dose corticosteroid therapy (> 10 mg/day) for over 6 months and not within the last 6 months.
12. Anticonvulsant therapy. (Dilantin, Phenobarbital)
13. High dose thiazide therapy (> 37.5 mg).
14. 24 hour urine calcium > 290 mg on 2 baseline tests.
15. Serum calcium exceeding upper normal limit on 2 baseline tests.
16. BMD. T-score less than -3.0 for spine or hip.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: HEALTH_SERVICES_RESEARCH
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: A1 vitamin D3 400IU; Orally for one year	Dietary supplement: vitamin D3; Oral, one capsule daily of vitamin D3 (400IU, 800IU, 1600 IU, or 2400IU) plus calcium citrate (1-4 tablets) twice daily to reach a total calcium intake of 1000-1200 mg/day; Other Names: Calcium citrate (Citracal)
PLACEBO_COMPARATOR: A2 vitamin D3 800IU; Orally for one year	Dietary supplement: vitamin D3; Oral, one capsule daily of vitamin D3 (400IU, 800IU, 1600 IU, or 2400IU) plus calcium citrate (1-4 tablets) twice daily to reach a total calcium intake of 1000-1200 mg/day; Other Names: Calcium citrate (Citracal)
PLACEBO_COMPARATOR: A3 vitamin D3 1600IU; Orally for one year	Dietary supplement: vitamin D3; Oral, one capsule daily of vitamin D3 (400IU, 800IU, 1600 IU, or 2400IU) plus calcium citrate (1-4 tablets) twice daily to reach a total calcium intake of 1000-1200 mg/day; Other Names: Calcium citrate (Citracal)
PLACEBO_COMPARATOR: A4 Vitamin D3 2400 IU; Orally for one year	Dietary supplement: vitamin D3; Oral, one capsule daily of vitamin D3 (400IU, 800IU, 1600 IU, or 2400IU) plus calcium citrate (1-4 tablets) twice daily to reach a total calcium intake of 1000-1200 mg/day; Other Names: Calcium citrate (Citracal)
PLACEBO_COMPARATOR: Placebo; Placebo for one year	Dietary supplement: vitamin D3; Oral, one capsule daily of vitamin D3 (400IU, 800IU, 1600 IU, or 2400IU) plus calcium citrate (1-4 tablets) twice daily to reach a total calcium intake of 1000-1200 mg/day; Other Names: Calcium citrate (Citracal)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Serum 25hydroxyvitamin D	Baseline, Change from Baseline at 6 Months and 12 Months
Parathyroid hormone	Baseline, Change from Baseline at 6 Months and 12 Months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
serum and urine calcium		Baseline, Change from Baseline at 6 Months, 9 Months and 12 Months
calcium absorption	radioactive calcium absorption is measured at baseline and end of study	Baseline, Change from Baseline at 12 Months
Bone density	bone density	Baseline, Change from Baseline at 12 Months
physical performance battery		Baseline, Change from Baseline at 12 Months
Forced Expiratory Volume FEV1	spirometry	Baseline, Change from Baseline at 12 Months
bone markers	serum osteocalcin,serum N-telopeptides	Baseline, Change from Baseline at 12 Months
Serum 1,25-dihydroxyvitamin D3	serum test	Baseline, Change from Baseline at 12 Months
skin color	measurement of sin color through the study using an IMS smart probe	Baseline, Change from Baseline at 6 Months and 12 Months
Serum 24,25dihydroxyvitamin D	measurement of serum 24,24(OH)2D by LCMS( liquid chromatography mass spectrophotometry	Baseline, Change from Baseline at 12 Months

Collaborators and Investigators

• Sponsor: Creighton University
• Collaborators: University of Nebraska

Publications and helpful links

General Publications

• Gallagher JC, Kinyamu HK, Fowler SE, Dawson-Hughes B, Dalsky GP, Sherman SS. Calciotropic hormones and bone markers in the elderly. J Bone Miner Res. 1998 Mar;13(3):475-82. doi: 10.1359/jbmr.1998.13.3.475.
• Aloia JF, Talwar SA, Pollack S, Feuerman M, Yeh JK. Optimal vitamin D status and serum parathyroid hormone concentrations in African American women. Am J Clin Nutr. 2006 Sep;84(3):602-9. doi: 10.1093/ajcn/84.3.602.
• Holick MF, Siris ES, Binkley N, Beard MK, Khan A, Katzer JT, Petruschke RA, Chen E, de Papp AE. Prevalence of Vitamin D inadequacy among postmenopausal North American women receiving osteoporosis therapy. J Clin Endocrinol Metab. 2005 Jun;90(6):3215-24. doi: 10.1210/jc.2004-2364. Epub 2005 Mar 29.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (ACTUAL): August 1, 2011
• Study Completion (ACTUAL): August 1, 2011

Study Registration Dates

• First Submitted: April 17, 2008
• First Submitted That Met QC Criteria: April 18, 2008
• First Posted (ESTIMATE): April 21, 2008

Study Record Updates

• Last Update Posted (ESTIMATE): March 25, 2016
• Last Update Submitted That Met QC Criteria: March 24, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Vitamin D insufficiency,vitamin D3 treatment,young women
• Additional Relevant MeSH Terms: Metabolic Diseases; Nutrition Disorders; Musculoskeletal Diseases; Deficiency Diseases; Malnutrition; Bone Diseases; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Vitamin D Deficiency; Rickets; Avitaminosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Cholecalciferol
• Other Study ID Numbers: PR065013; DOD. CDMRP. W81XWH-07-1-0201 (OTHER_GRANT: Department of Defense)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO