Clinical trial NCT00423358: Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Official title: Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Hypovitaminosis D
Keywords: rheumatoid arthritis
hypovitaminosis D
bone turnover
ergocalciferol
Lead sponsor: University of Wisconsin, Madison
Sponsor class: OTHER
Collaborators: name: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
First posted: 2007-01-18
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

* Rheumatology

Exclusion Criteria:

* Bisphosphonate therapy

Primary outcomes:
measure: Parathyroid Hormone Level
timeFrame: 1 Year
Secondary outcomes:
measure: Bone Mineral Density
timeFrame: 1 Year
measure: Short Form 36 Survey
timeFrame: 1 Year
Other outcomes:
Locations:
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
Study officials:
affiliation: University of Wisconsin, Madison
name: Karen E Hansen, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.