Clinical trial NCT00933244: Treatment of Vitamin D Insufficiency
Official title: Treatment of Vitamin D Insufficiency
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Vitamin D Deficiency
Keywords: Vitamin D
Cholecalciferol
Parathyroid Hormone
Calcium Absorption
Bone Mineral Density
Muscle Function
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institutes of Health (NIH)
name: National Institute on Aging (NIA)
First posted: 2009-07-07
Enrollment: 230
Sex: FEMALE
Maximum age (years): 75
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to answer the following questions: Does vitamin D increase calcium absorption, bone mass and muscle mass and function in women past menopause who have mildly low vitamin D levels? Do these benefits require prescription-strength vitamin D, or is an over the counter vitamin D dose enough?

Detailed description: Osteoporosis is a major health problem in postmenopausal women. At age 50, half of women will suffer an osteoporotic fracture in their remaining lifetime, causing increased disability and mortality. Vitamin D deficiency, defined as a serum 25(OH)D \<15 ng/mL, contributes to osteoporosis via decreased calcium absorption (Ca·Ab), secondary hyperparathyroidism (HPT), increased bone resorption and decreased bone mineral density (BMD). Thus, experts agree that patients with vitamin D deficiency should receive vitamin D therapy.

Vitamin D insufficiency (VDI) is a milder form of hypovitaminosis D defined as a 25(OH)D level between 15 and 30 ng/mL regardless of parathyroid hormone (PTH) status. Experts disagree on whether to treat VDI, as the clinical benefits of therapy are uncertain. Some experts insist the optimal 25(OH)D level is ≥30 ng/mL. By contrast, both the Food and Nutrition Board and NIH Evidence Report No. 158 state that insufficient evidence exists to declare the optimal serum 25(OH)D for bone health, despite review of \~170 studies. Consequently, the Food and Nutrition Board cannot determine a recommended daily allowance for vitamin D. Confusion over the optimal 25(OH)D level results, in part, because previous trials failed to recruit subjects based on initial 25(OH)D levels and/or failed to target or achieve 25(OH)D levels ≥30 ng/mL. Moreover, secondary HPT, the proposed mechanism by which VDI causes bone loss, occurs in only 10% to 33% of people with VDI. As such, people with VDI and normal PTH might not experience clinical benefits from vitamin D therapy. VDI is widespread, affecting 26% to 39% of postmenopausal American women with and without osteoporosis. Therefore, determining the ideal 25(OH)D level for optimal calcium homeostasis and bone health is of utmost clinical and public health importance. Our overall goal, congruent with Healthy People 2010 objective 2-9, is to evaluate the effect of vitamin D therapy on the risk of osteoporosis in postmenopausal women with VDI, as reflected by changes in Ca·Ab, BMD and muscle fitness. Our second goal is to evaluate whether a high-dose vitamin D regimen, chosen to achieve and maintain a 25(OH)D level ≥30 ng/mL, is superior in its effects on study outcomes compared to a low-dose vitamin D regimen that can permit continued VDI.

We will conduct a randomized, placebo-controlled double-blind trial of low-dose and high-dose vitamin D in postmenopausal women with vitamin D insufficiency in order to investigate the following aims:

1. To evaluate the effect of vitamin D3 therapy on Ca·Ab in postmenopausal women less than or equal to 75 years old with VDI. Sub-aims include the investigation of subject variables influencing Ca·Ab and 25(OH)D levels at baseline and one month, the accuracy of oral isotope plasma levels for Ca·Ab measurement and the ability of a questionnaire to identify patients with low vitamin D status.
2. To evaluate the effects of vitamin D3 therapy on the 12-month change in BMD and bone turnover in the same trial conducted for Aim 1. Sub-aims include the identification of subject variables significantly influencing change in BMD and an evaluation of the relationship between changes in Ca·Ab and changes in BMD.
3. To evaluate the effect of vitamin D therapy on muscle mass and functional capacity in the same trial conducted for Aim 1. We will measure muscle mass by whole body bone densitometry and assess muscle function using the Timed Up and Go (TUG) Test and the modified Stanford Health Assessment Questionnaire (HAQ) score. Sub-aims include the identification of subject variables significantly influencing muscle outcomes.

Eligibility criteria: Inclusion Criteria:

* Vitamin D insufficiency, defined as a serum 25(OH)D 16 to 25 ng/mL by high performance liquid chromotography assay
* Women ≥ 5 years past the date of last menses or bilateral oophorectomy, or ≥ 60 years old if they had prior hysterectomy without bilateral oophorectomy
* Total dietary and supplemental calcium intake \< 600 mg daily but ≤ 1,400 mg daily, based on a food frequency questionnaire

Exclusion Criteria:

* Women \> 75 years old
* Hypercalcemia (serum calcium corrected for albumin \> 10.4 mg/dL)
* Nephrolithiasis by medical record or patient report
* Inflammatory bowel disease, malabsorption or chronic diarrhea
* Stage 3, 4 or 5 Chronic Kidney Disease based on the Modification of Renal Diet (MDRD) formula
* Use of bone-active medications within the past 6 months including bisphosphonates, estrogen compounds, calcitonin, teriparatide, oral corticosteroids and anticonvulsants
* Allergy or intolerance to orange juice
* Allergy or intolerance to sunscreen
* Prior adult clinical fragility fracture of the hip, spine or wrist or a T-score below -2.5 at the lumbar spine or femur

Primary outcomes:
measure: Intestinal Calcium Absorption
timeFrame: One Year
Secondary outcomes:
measure: Bone Mineral Density
timeFrame: 1 Year
Other outcomes:
measure: Bone Turnover
timeFrame: 0, 30, 60, 120, 365 days
measure: Muscle Function: One Year Change in Timed Up and Go Test, Five Sit-to-Stand Test
timeFrame: 1 Year
Locations:
city: Madison
country: United States
facility: University of Wisconsin School of Medicine and Public Health
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Karen E Hansen, MD, MS
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hansen KE, Jones AN, Lindstrom MJ, Davis LA, Engelke JA, Shafer MM. Vitamin D insufficiency: disease or no disease? J Bone Miner Res. 2008 Jul;23(7):1052-60. doi: 10.1359/jbmr.080230.
citation: Ramsubeik K, Keuler NS, Davis LA, Hansen KE. Factors associated with calcium absorption in postmenopausal women: a post hoc analysis of dual-isotope studies. J Acad Nutr Diet. 2014 May;114(5):761-7. doi: 10.1016/j.jand.2013.07.041. Epub 2013 Oct 24.
citation: Nabak AC, Johnson RE, Keuler NS, Hansen KE. Can a questionnaire predict vitamin D status in postmenopausal women? Public Health Nutr. 2014 Apr;17(4):739-46. doi: 10.1017/S1368980013001973. Epub 2013 Jul 22.
citation: Hansen KE, Johnson RE, Chambers KR, Johnson MG, Lemon CC, Vo TN, Marvdashti S. Treatment of Vitamin D Insufficiency in Postmenopausal Women: A Randomized Clinical Trial. JAMA Intern Med. 2015 Oct;175(10):1612-21. doi: 10.1001/jamainternmed.2015.3874.
citation: Vreede AP, Jones AN, Hansen KE. Can serum isotope levels accurately measure intestinal calcium absorption compared to gold-standard methods? Nutr J. 2015 Jul 31;14:73. doi: 10.1186/s12937-015-0065-5.