Treatment of Hypovitaminosis D in Rheumatoid Arthritis

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00423358
First received: January 17, 2007
Last updated: July 27, 2015
Last verified: July 2015

January 17, 2007
July 27, 2015
February 2005
August 2008   (final data collection date for primary outcome measure)
Parathyroid Hormone Level [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
Serum parathyroid hormone level
Bone Turnover
Complete list of historical versions of study NCT00423358 on ClinicalTrials.gov Archive Site
  • Bone Mineral Density [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    one year change in mean total hip BMD
  • Short Form 36 Survey [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    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
  • Bone Mineral Density
  • SF-36
Not Provided
Not Provided
 
Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Treatment of Hypovitaminosis D in Rheumatoid Arthritis

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.

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.

Interventional
Not Provided
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
  • Rheumatoid Arthritis
  • Hypovitaminosis D
  • Dietary Supplement: Vitamin D
    Ergocalciferol 50,000 IU loading dose then twice monthly for one year
    Other Name: ergocalciferol
  • Dietary Supplement: placebo
    matching placebo
    Other Name: placebo
  • Active Comparator: vitamin D
    ergocalciferol 50,000 IU Twice monthly
    Intervention: Dietary Supplement: Vitamin D
  • Placebo Comparator: placebo
    matching placebo tablet
    Intervention: Dietary Supplement: placebo

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
22
February 2009
August 2008   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Rheumatology

Exclusion Criteria:

  • Bisphosphonate therapy
Both
18 Years to 90 Years
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00423358
2004-0011, K23AR050995
Yes
University of Wisconsin, Madison
University of Wisconsin, Madison
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Principal Investigator: Karen E Hansen, MD University of Wisconsin, Madison
University of Wisconsin, Madison
July 2015

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP