Clinical trial NCT00662844: Vitamin D Supplementation in Younger Women
Official title: Optimum Vitamin D Nutrition in Young Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hypovitaminosis D
Keywords: Vitamin D insufficiency,vitamin D3 treatment,young women
Lead sponsor: Creighton University
Sponsor class: OTHER
Collaborators: name: University of Nebraska
First posted: 2008-04-21
Enrollment: 198
Sex: FEMALE
Minimum age (years): 25
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

Brief summary: 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

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serum 25hydroxyvitamin D
timeFrame: Baseline, Change from Baseline at 6 Months and 12 Months
measure: Parathyroid hormone
timeFrame: Baseline, Change from Baseline at 6 Months and 12 Months
Secondary outcomes:
measure: serum and urine calcium
timeFrame: Baseline, Change from Baseline at 6 Months, 9 Months and 12 Months
measure: calcium absorption
timeFrame: Baseline, Change from Baseline at 12 Months
measure: Bone density
timeFrame: Baseline, Change from Baseline at 12 Months
measure: physical performance battery
timeFrame: Baseline, Change from Baseline at 12 Months
measure: Forced Expiratory Volume FEV1
timeFrame: Baseline, Change from Baseline at 12 Months
measure: bone markers
timeFrame: Baseline, Change from Baseline at 12 Months
measure: Serum 1,25-dihydroxyvitamin D3
timeFrame: Baseline, Change from Baseline at 12 Months
measure: skin color
timeFrame: Baseline, Change from Baseline at 6 Months and 12 Months
measure: Serum 24,25dihydroxyvitamin D
timeFrame: Baseline, Change from Baseline at 12 Months
Other outcomes:
Locations:
Study officials:
affiliation: Creighton University Medical Center
name: J C Gallagher, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.