Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Primary Purpose
Rheumatoid Arthritis, Hypovitaminosis D
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Vitamin D
placebo
Sponsored by
About this trial
This is an interventional treatment trial for Rheumatoid Arthritis focused on measuring rheumatoid arthritis, hypovitaminosis D, bone turnover, ergocalciferol
Eligibility Criteria
Inclusion Criteria:
- Rheumatology
Exclusion Criteria:
- Bisphosphonate therapy
Sites / Locations
- University of Wisconsin
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Placebo Comparator
Arm Label
vitamin D
placebo
Arm Description
ergocalciferol 50,000 IU Twice monthly
matching placebo tablet
Outcomes
Primary Outcome Measures
Parathyroid Hormone Level
Serum parathyroid hormone level
Secondary Outcome Measures
Bone Mineral Density
one year change in mean total hip BMD
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
Full Information
NCT ID
NCT00423358
First Posted
January 17, 2007
Last Updated
July 27, 2015
Sponsor
University of Wisconsin, Madison
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
1. Study Identification
Unique Protocol Identification Number
NCT00423358
Brief Title
Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Official Title
Treatment of Hypovitaminosis D in Rheumatoid Arthritis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2015
Overall Recruitment Status
Completed
Study Start Date
February 2005 (undefined)
Primary Completion Date
August 2008 (Actual)
Study Completion Date
February 2009 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis, Hypovitaminosis D
Keywords
rheumatoid arthritis, hypovitaminosis D, bone turnover, ergocalciferol
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
22 (Actual)
8. Arms, Groups, and Interventions
Arm Title
vitamin D
Arm Type
Active Comparator
Arm Description
ergocalciferol 50,000 IU Twice monthly
Arm Title
placebo
Arm Type
Placebo Comparator
Arm Description
matching placebo tablet
Intervention Type
Dietary Supplement
Intervention Name(s)
Vitamin D
Other Intervention Name(s)
ergocalciferol
Intervention Description
Ergocalciferol 50,000 IU loading dose then twice monthly for one year
Intervention Type
Dietary Supplement
Intervention Name(s)
placebo
Intervention Description
matching placebo
Primary Outcome Measure Information:
Title
Parathyroid Hormone Level
Description
Serum parathyroid hormone level
Time Frame
1 Year
Secondary Outcome Measure Information:
Title
Bone Mineral Density
Description
one year change in mean total hip BMD
Time Frame
1 Year
Title
Short Form 36 Survey
Description
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
Time Frame
1 Year
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Rheumatology
Exclusion Criteria:
Bisphosphonate therapy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Karen E Hansen, MD
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Wisconsin
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53705
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
18302509
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.
Results Reference
result
PubMed Identifier
24561419
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.
Results Reference
result
Learn more about this trial
Treatment of Hypovitaminosis D in Rheumatoid Arthritis
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