Treatment of Hypovitaminosis D in Rheumatoid Arthritis

Not Applicable

Completed

• Conditions: Rheumatoid Arthritis; Hypovitaminosis D
• Interventions: Dietary Supplement: Vitamin D; Dietary Supplement: placebo

• Registration Number: NCT00423358
• Lead Sponsor: 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.

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 Timeline

• Study Start: 2005-02
• Study First Submitted: 2007-01-17
• Study First Submitted QC: 2007-01-17
• Study First Posted: 2007-01-18
• Primary Completion: 2008-08
• Study Completion: 2009-02
• Results First Submitted: 2015-05-29
• Status Verified: 2015-07
• Results First Submitted QC: 2015-07-27
• Last Update Submitted: 2015-07-27
• Results First Posted: 2015-08-24
• Last Update Posted: 2015-08-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 22

Inclusion Criteria

• Rheumatology

Exclusion Criteria

• Bisphosphonate therapy

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
vitamin D	Vitamin D	ergocalciferol 50,000 IU Twice monthly
placebo	placebo	matching placebo tablet

Primary Outcome Measures

Name	Time	Method
Parathyroid Hormone Level	1 Year	Serum parathyroid hormone level

Secondary Outcome Measures

Name	Time	Method
Bone Mineral Density	1 Year	one year change in mean total hip BMD
Short Form 36 Survey	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

Trial Locations

Locations (1)

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States