Treatment of Hypovitaminosis D in Rheumatoid Arthritis

NCT ID: NCT00423358

Last Updated: 2015-08-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 22 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-02-28
• Study Completion Date: 2009-02-28

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.

Conditions

Rheumatoid Arthritis; Hypovitaminosis D

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

vitamin D

ergocalciferol 50,000 IU Twice monthly

Group Type: ACTIVE_COMPARATOR

Vitamin D

Intervention Type: DIETARY_SUPPLEMENT

Ergocalciferol 50,000 IU loading dose then twice monthly for one year

placebo

matching placebo tablet

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DIETARY_SUPPLEMENT

matching placebo

Interventions

Vitamin D

Ergocalciferol 50,000 IU loading dose then twice monthly for one year

Intervention Type: DIETARY_SUPPLEMENT

placebo

matching placebo

Intervention Type: DIETARY_SUPPLEMENT

Other Intervention Names

ergocalciferol

Eligibility Criteria

Inclusion Criteria

• Rheumatology

Exclusion Criteria

• Bisphosphonate therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

NIH

Sponsor Role: collaborator

University of Wisconsin, Madison

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Karen E Hansen, MD

Role: PRINCIPAL_INVESTIGATOR

University of Wisconsin, Madison

Locations

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

References

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.

Reference Type: RESULT

PMID: 18302509 (View on PubMed)

Hansen KE, Bartels CM, Gangnon RE, Jones AN, Gogineni J. An evaluation of high-dose vitamin D for rheumatoid arthritis. J Clin Rheumatol. 2014 Mar;20(2):112-4. doi: 10.1097/RHU.0000000000000072. No abstract available.

Reference Type: RESULT

PMID: 24561419 (View on PubMed)

Other Identifiers

K23AR050995

Identifier Type: NIH

Identifier Source: secondary_id

View Link

2004-0011

Identifier Type: -

Identifier Source: org_study_id