Treatment of Hypovitaminosis D in Rheumatoid Arthritis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00423358
Recruitment Status : Completed
First Posted : January 18, 2007
Results First Posted : August 24, 2015
Last Update Posted : August 24, 2015
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
This study recruits individuals with rheumatoid arthritis (RA) and low vitamin D concentrations. Subjects are dosed with vitamin D or placebo for one year. Primary outcome is change in bone turnover markers, additionally, bone mineral density and parameters of RA status are evaluated throughout the study.

Condition or disease Intervention/treatment Phase
Rheumatoid Arthritis Hypovitaminosis D Dietary Supplement: Vitamin D Dietary Supplement: placebo Not Applicable

Detailed Description:

Osteoporosis is twice as common in people with rheumatoid arthritis (RA), compared to age and gender-matched controls [1, 2]. Hypovitaminosis D can contribute to osteoporosis pathogenesis by decreasing calcium absorption, leading to a decline in serum ionized calcium, a rise in parathyroid hormone levels and upregulation of osteoclast activity, leading to loss of calcium from the skeleton. Hypovitaminosis D is also common in patients with rheumatoid arthritis [3-5], making it an appealing target to potentially improve health in both RA and osteoporosis.

Vitamin D has theoretic potential to modulate RA disease activity, based on the presence of vitamin D receptors in lymphocytes, macrophages, chondrocytes, and synovial cells [6]. Vitamin D, given as the bioactive metabolite 1,25(OH)2D, ameliorates disease activity in murine models of RA [7, 8]. However, few studies have evaluated the effect of vitamin D on RA disease activity in humans. Two three month open-label studies reported that vitamin D reduced RA disease activity [9] and pain levels [10]. By contrast, an eight-week open-label study [11] reported no reduction in swollen joint counts, inflammatory markers or cytokine levels after vitamin D therapy. The only double-blind, placebo-controlled trial published thus far [12] found no significant effect of vitamin D on RA disease activity, but was limited by the lack of hypovitaminosis D as a criterion for study entry. Indeed, at baseline subjects' mean 25(OH)D levels indicated vitamin D repletion, potentially explaining the null effect of vitamin D on RA disease activity.

Three studies have evaluated the effect of vitamin D on bone mineral density (BMD) in patients with RA [13-15]. Researchers [14] randomized 96 subjects with RA to vitamin D (500 IU/day) and calcium (1000 mg/day) or placebo for two years; vitamin D and calcium therapy modestly increased BMD in the spine and hip. In another study [15], 20 subjects randomized to daily calcium and 1 α-hydroxyvitamin D for up to 24 months experienced similar declines in radius and spine BMD compared to 15 controls [15]. Likewise, vitamin D and calcium did not prevent bone loss in a prospective cohort study of patients with RA [13]. However, none of the studies required hypovitaminosis D as an entry criterion, vitamin D repletion to 25(OH)D levels > 32 ng/ml were not evaluated [13, 14] or achieved [15], and low doses of vitamin D were administered, potentially limiting skeletal benefits of this therapy.

We hypothesized that correction of hypovitaminosis D in subjects with RA would decrease parathyroid hormone (PTH), increase BMD, improve functional capacity and down-regulate inflammatory cytokine production, thereby diminishing disease activity. Vitamin D is inexpensive and widely available. If proven beneficial, vitamin D might become a mainstay of therapy for subjects with RA.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Study Start Date : February 2005
Actual Primary Completion Date : August 2008
Actual Study Completion Date : February 2009

Arm Intervention/treatment
Active Comparator: vitamin D
ergocalciferol 50,000 IU Twice monthly
Dietary Supplement: Vitamin D
Ergocalciferol 50,000 IU loading dose then twice monthly for one year
Other Name: ergocalciferol

Placebo Comparator: placebo
matching placebo tablet
Dietary Supplement: placebo
matching placebo

Primary Outcome Measures :
  1. Parathyroid Hormone Level [ Time Frame: 1 Year ]
    Serum parathyroid hormone level

Secondary Outcome Measures :
  1. Bone Mineral Density [ Time Frame: 1 Year ]
    one year change in mean total hip BMD

  2. Short Form 36 Survey [ Time Frame: 1 Year ]
    12 month score for physical function domain of SF36 survey; scale 0 to 100 with 0 indicating worst disability and 100 indicating best physical function

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Rheumatology

Exclusion Criteria:

  • Bisphosphonate therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00423358

United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Wisconsin, Madison
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Karen E Hansen, MD University of Wisconsin, Madison

Publications of Results:
Responsible Party: University of Wisconsin, Madison Identifier: NCT00423358     History of Changes
Other Study ID Numbers: 2004-0011
K23AR050995 ( U.S. NIH Grant/Contract )
First Posted: January 18, 2007    Key Record Dates
Results First Posted: August 24, 2015
Last Update Posted: August 24, 2015
Last Verified: July 2015

Keywords provided by University of Wisconsin, Madison:
rheumatoid arthritis
hypovitaminosis D
bone turnover

Additional relevant MeSH terms:
Arthritis, Rheumatoid
Vitamin D Deficiency
Joint Diseases
Musculoskeletal Diseases
Rheumatic Diseases
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases
Deficiency Diseases
Nutrition Disorders
Bone Diseases, Metabolic
Bone Diseases
Metabolic Diseases
Calcium Metabolism Disorders
Vitamin D
Growth Substances
Physiological Effects of Drugs
Bone Density Conservation Agents