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.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis; Hypovitaminosis D
• Intervention / Treatment: Dietary supplement: placebo; Dietary supplement: Vitamin D

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
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • Madison, Wisconsin, United States, 53705
      • University of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Rheumatology

Exclusion Criteria:

• Bisphosphonate therapy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: ergocalciferol
Placebo Comparator: placebo; matching placebo tablet	Dietary supplement: placebo; matching placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Parathyroid Hormone Level	Serum parathyroid hormone level	1 Year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Mineral Density	one year change in mean total hip BMD	1 Year
Short Form 36 Survey	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	1 Year

Collaborators and Investigators

• Sponsor: University of Wisconsin, Madison
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)

Publications and helpful links

General Publications

• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: February 1, 2005
• Primary Completion (Actual): August 1, 2008
• Study Completion (Actual): February 1, 2009

Study Registration Dates

• First Submitted: January 17, 2007
• First Submitted That Met QC Criteria: January 17, 2007
• First Posted (Estimate): January 18, 2007

Study Record Updates

• Last Update Posted (Estimate): August 24, 2015
• Last Update Submitted That Met QC Criteria: July 27, 2015
• Last Verified: July 1, 2015

More Information

Terms related to this study

• Keywords: rheumatoid arthritis; ergocalciferol; hypovitaminosis D; bone turnover
• Additional Relevant MeSH Terms: Metabolic Diseases; Immune System Diseases; Autoimmune Diseases; Nutrition Disorders; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Deficiency Diseases; Malnutrition; Bone Diseases; Bone Diseases, Metabolic; Calcium Metabolism Disorders; Arthritis; Arthritis, Rheumatoid; Vitamin D Deficiency; Rickets; Avitaminosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Ergocalciferols
• Other Study ID Numbers: 2004-0011; K23AR050995 (U.S. NIH Grant/Contract)