Ignite Creation Date:
2025-12-25 @ 12:03 AM
Ignite Modification Date:
2025-12-25 @ 10:01 PM
Study NCT ID:
NCT00423358
Status:
COMPLETED
Last Update Posted:
2015-08-24
First Post:
2007-01-17
Is NOT Gene Therapy:
False
Has Adverse Events:
True
Brief Title:
Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Sponsor:
University of Wisconsin, Madison
Organization:
Study Overview
Official Title:
Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Status:
COMPLETED
Status Verified Date:
2015-07
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
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.
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 Oversight
Has Oversight DMC:
True
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
Secondary ID Infos
| Secondary ID | Type | Domain | Link | View |
|---|---|---|---|---|
| K23AR050995 | NIH | None | https://reporter.nih.gov/quic… | View |