Treatment of Vitamin D Insufficiency

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00933244
First received: July 2, 2009
Last updated: August 7, 2014
Last verified: August 2014
  Purpose

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?


Condition Intervention Phase
Vitamin D Insufficiency
Drug: High Dose Vitamin D3
Drug: Low Dose Vitamin D3
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Treatment of Vitamin D Insufficiency

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Intestinal Calcium Absorption [ Time Frame: One Year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Bone Mineral Density [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • Bone Turnover [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
  • Muscle Function [ Time Frame: 1 Year ] [ Designated as safety issue: No ]

Enrollment: 230
Study Start Date: April 2010
Study Completion Date: August 2014
Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: High Dose Vitamin D

Loading Dose: 50,000 International Units vitamin D3 gel-caps (yellow) to take daily for 15 days and placebo gel-caps (white) to take daily for 15 days.

Maintenance Dose: 50,000 International Units vitamin D3 gel-caps (yellow) to take two times a month for 350 days and placebo gel-caps (white) to take daily for 350 days.

Drug: High Dose Vitamin D3
Yellow gel-cap vitamin D3 at 50,000 International Units to take orally, daily for 15 days then two times a month for 350 days.
Other Names:
  • Vitamin D
  • Cholecalciferol
Drug: Placebo
White gel-cap placebo pills to take orally, daily for 355 days.
Other Name: sugar pill
Active Comparator: Low Dose Vitamin D

Loading Dose: 800 International Units vitamin D3 gel-caps (white) to take daily for 15 days plus placebo gel-caps (yellow) to take daily for 15 days.

Maintenance Dose: 800 International Units vitamin D3 gel-caps (white) to take daily for 350 days plus placebo gel-caps (yellow) to take two times a month for 350 days.

Drug: Low Dose Vitamin D3
White gel-cap vitamin D3 at 800 International Units to take orally, daily for 355 days
Other Names:
  • Vitamin D
  • Cholecalciferol
Drug: Placebo
Yellow gel-cap placebo pills to take orally, daily for 15 days then two times a month for 350 days.
Other Name: sugar pill
Placebo Comparator: Placebo

Loading Dose: Placebo gel-caps (yellow) to take daily for 15 days plus placebo gel-caps (white) to take daily for 15 days.

Maintenance Dose: Placebo gel-caps (yellow) to take two times a month for 350 days plus placebo gel-caps (white) to take daily for 350 days.

Drug: Placebo
Yellow gel-cap placebo pills to take orally, daily for 15 days then two times a month for 350 days.
Other Name: sugar pill
Drug: Placebo
White gel-cap placebo pills to take orally, daily for 355 days.
Other Name: sugar pill

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

Ages Eligible for Study:   up to 75 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00933244

Locations
United States, Wisconsin
University of Wisconsin School of Medicine and Public Health
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Principal Investigator: Karen E Hansen, MD, MS University of Wisconsin, Madison
  More Information

Publications:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00933244     History of Changes
Other Study ID Numbers: H-2009-0055, AG028739-01A2
Study First Received: July 2, 2009
Last Updated: August 7, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
Vitamin D
Cholecalciferol
Parathyroid Hormone
Calcium Absorption
Bone Mineral Density
Muscle Function

Additional relevant MeSH terms:
Vitamins
Vitamin D
Ergocalciferols
Cholecalciferol
Micronutrients
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Bone Density Conservation Agents

ClinicalTrials.gov processed this record on October 19, 2014