Vitamin D Supplementation in Older Women

Aging Clinical Trial

— VIDOS  

Official title:

Determination of RDA for Vitamin D in Caucasian and African American Women

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00472823
• Other study ID #: AG0081
• Secondary ID: 1R01AG028168-01
• Status: Completed
• Phase: N/A
• First received: May 10, 2007
• Last updated: March 11, 2016
• Start date: April 2007
• Est. completion date: August 2011

Study information

• Verified date: March 2016
• Source: Creighton University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to examine the effects of several doses of vitamin D on hormones related to bone, calcium absorption, bone density and muscle strength.

Description:

The prevalence of osteoporosis is high in the United States, with about 10 million people over the age of 50 already having the disease and another 34 million at risk for developing it. Development of low-cost and effective strategies is important for preventing osteoporosis and reducing osteoporotic fractures. A simple inexpensive strategy to prevent osteoporosis is adequate nutrition with calcium and vitamin D. Serum 25OHD (25-hydroxyvitamin D) is now accepted as the objective measure of vitamin D nutrition. There is a growing understanding that serum 25OHD concentrations of at least 30-32 ng/ml are needed for optimal bone health at which serum parathyroid hormone (PTH) concentrations reach a minimum.

There are no systematic prospective dose response studies aimed at determining the optimum amount of vitamin D intake required to maintain optimum serum 25OHD levels in the population which will help in determining the estimated average requirement (EAR) and recommended dietary requirement (RDA) for vitamin D. More work to determine the RDA for vitamin D has been recommended by the Panel on Calcium and Related Nutrients of the Food and Nutrition Board. This study is aimed at filling the information gap by concentrating on the high risk group of postmenopausal women. We are testing the theory that increasing serum 25OHD to a level greater than 30 ng/ml will reduce serum PTH in the high risk group of vitamin D insufficient postmenopausal women with an adequate intake of calcium. We also believe that the dose of vitamin D that will achieve this level is approximately 4400IU per day, which is well above the suggested adequate intake of 400-600 ID recommended for the elderly.

In a one year double blind, randomized prospective clinical trial, we will examine the dose response effect of supplementation with different doses of vitamin D3 (400, 800, 1600, 2400, 3200, 4000, 4800IU/day) on the primary outcomes of serum 25OHD and PTH in 160 postmenopausal Caucasian and 160 African American women who have inadequate vitamin D levels in winter. We expect that the results from this study will add useful and important information about the RDA for vitamin D for postmenopausal women who are more susceptible to osteoporosis. The results from this study will also help in designing future clinical trials to study the effect of vitamin D, for example in preventing fractures, falls, cancer.

The main objective of the current proposal is to study the effect of increasing doses of vitamin D3 in the high risk group of postmenopausal Caucasian and African American women with hypovitaminosis D (serum 25OHD <20 ng/ml) in winter in presence of sufficient calcium intake, in order to determine the Estimated Average Requirement (EAR) that covers 50% and the Recommended Daily allowance (RDA) covers 97.5% of population for vitamin D. We will use a serum 25OHD concentration equal >30 ng/ml and normalization of serum PTH as indicators of adequacy. We expect that the results from this proposal will add important information helpful in designing future larger clinical trials to determine the recommended dietary allowance (RDA) for vitamin D in other ethnic groups and designing clinical trials on the effect of vitamin D on falls and fractures.

We hypothesize that increasing serum 25OHD to a level greater than 30 ng/ml with vitamin D supplements in 97 percent of the study subjects will reduce serum PTH and bone markers to premenopausal range. We postulate that the RDA of vitamin D that will achieve a serum 25OHD of ≥ 30 ng/ml in 97.5% of women during winter is approximately 4400 IU/d and the EAR dose of vitamin D is between 800-1000 IU.

The specific aims of the proposal are,

1. To examine the dose response effect of vitamin D3, 400, 800, 1600, 2400, 3200, 4000, and 4800 IU /d in postmenopausal Caucasian and African American women with hypovitaminosis D (serum 25OHD equal <20 ng/ml) in winter plus an adequate calcium intake compared to a calcium control group, on serum 25OHD and PTH levels, which constitute our primary outcome measures.

2. To determine the EAR and RDA for postmenopausal women by establishing the dose of vitamin D3 that will increase serum 25OHD above 30 ng/ml in 97.5% of study subjects in winter and reduce serum PTH to the normal premenopausal range.

3. To study the dose response effect of vitamin D3 on calcium absorption, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) serum calcium, serum bone markers, bone mineral density (BMD) and falls (only in elderly) (the secondary outcome measures)

4. To establish the long term safety of these doses relating to hypercalcemia and hypercalciuria

Progress: Caucasian enrollment completed July 2008; African American enrollment completed May 2009

Recruitment information / eligibility

• Status: Completed
• Enrollment: 273
• Est. completion date: August 2011
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 57 Years and older

Eligibility

Inclusion Criteria:

• At least 7 years post-menopause

• Serum 25OHD level 5 ng/ml to 20 ng/ml

• BMI less than or equal to 40 kg/m2

• Willing to discontinue multivitamins that contain vitamin D during the study

Exclusion Criteria:

• Cancer (except basal cell carcinoma) or terminal illness

• Previous hip fracture

• Hemiplegia (paralysis of one side of the body)

• Uncontrolled type I diabetes or fasting blood sugar greater than 140 mg in type II

• Kidney stones more than twice in a lifetime

• Chronic renal failure

• Evidence of chronic liver disease, including alcoholism

• Physical conditions such as severe osteoarthritis, rheumatoid arthritis, heart failure severe enough to prevent reasonable physical activity

• Previous treatment with bisphosphonates (more that 3 months), PTH or PTH derivatives, (e.g. Teriparatide or Fluoride) in the last 6 months

• Previous treatment within the last 6 months with calcitonin or estrogen

• Chronic high dose corticosteroid therapy (more than 10 mg per day) for over 6 months and not within the last 6 months

• Anticonvulsant therapy

• High dose thiazide therapy (more than 37.5 mg)

• 24 hour urine calcium greater than 290 mg on 2 baseline tests

• Serum calcium exceeding upper normal limit on 2 baseline tests

• Bone Mineral Density T-score less than -3.0 for spine or hip

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Aging
• Osteoporosis

Intervention

Dietary Supplement:
• Vitamin D3
Orally for one year
• Calcium Citrate (Citracal)
Orally for one year; dosage adjusted so that calcium intake is 1200-1400mg daily

Locations

Country	Name	City	State
United States	Creighton University Medical Center	Omaha	Nebraska

Sponsors (4)

Lead Sponsor	Collaborator
Creighton University	National Institute on Aging (NIA), Office of Dietary Supplements (ODS), University of Nebraska

Country where clinical trial is conducted

United States, 

References & Publications (3)

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. — View 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. — View 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. Epub 2005 Mar 29. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Changes in Serum 25-hydroxyvitamin D (25OHD) and parathyroid hormone (PTH) levels		Baseline, 6months,12 months	No
Secondary	Calcium absorption	100mg calcium+ calcium45	Baseline and 12 months	No
Secondary	Serum/urine calcium		Baseline and every 3 months	Yes
Secondary	Bone markers		Baseline, and 12 months	No
Secondary	Bone density	spine,hip,total body,lateral	Baseline and 12 months	No
Secondary	Muscle strength	leg strength( Cybex),timed up and go,hand grip,chair stand,gait speed,quiet stance,postural stability( biodex),standing balance	Baseline,6 months,12 months	No
Secondary	Falls	questionnaire	Baseline and every 3 months	No
Secondary	Pulmonary function studies	FEV1	baseline and final test	No
Secondary	Genotyping		one time	No
Secondary	Molecular studies of peripheral leucocytes		baseline and final test	No
Secondary	Adult Depression Score	questionnaire	baseline and 12 months	No
Secondary	Physical Activity Scale form ( PASE)	questionnaire	baseline,6 months,12 months	No
Secondary	sun exposure	sun exposure form and skin color evaluation by a reflective meter (SmartProbe)	baseline and every 3 months	No
Secondary	Basic metabolic panel		baseline and every 3 months	No
Secondary	serum 1,25 dihydroxyvitamin D		baseline and 12 months	No
Secondary	quality of life	questionnaire	baseline and 12 months	No