Treatment of Hypovitaminosis D in Rheumatoid Arthritis

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT00423358
First received: January 17, 2007
Last updated: July 27, 2015
Last verified: July 2015
  Purpose

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.


Condition Intervention
Rheumatoid Arthritis
Hypovitaminosis D
Dietary Supplement: Vitamin D
Dietary Supplement: placebo

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: Treatment of Hypovitaminosis D in Rheumatoid Arthritis

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Parathyroid Hormone Level [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    Serum parathyroid hormone level


Secondary Outcome Measures:
  • Bone Mineral Density [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    one year change in mean total hip BMD

  • Short Form 36 Survey [ Time Frame: 1 Year ] [ Designated as safety issue: No ]
    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


Enrollment: 22
Study Start Date: February 2005
Study Completion Date: February 2009
Primary Completion Date: August 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: ergocalciferol
Placebo Comparator: placebo
matching placebo tablet
Dietary Supplement: placebo
matching placebo
Other Name: placebo

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

Ages Eligible for Study:   18 Years to 90 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Rheumatology

Exclusion Criteria:

  • Bisphosphonate therapy
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00423358

Locations
United States, Wisconsin
University of Wisconsin
Madison, Wisconsin, United States, 53705
Sponsors and Collaborators
University of Wisconsin, Madison
Investigators
Principal Investigator: Karen E Hansen, MD University of Wisconsin, Madison
  More Information

Publications:
Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00423358     History of Changes
Other Study ID Numbers: 2004-0011, K23AR050995
Study First Received: January 17, 2007
Results First Received: May 29, 2015
Last Updated: July 27, 2015
Health Authority: United States: Institutional Review Board

Keywords provided by University of Wisconsin, Madison:
rheumatoid arthritis
hypovitaminosis D
bone turnover
ergocalciferol

Additional relevant MeSH terms:
Rickets
Arthritis
Arthritis, Rheumatoid
Avitaminosis
Vitamin D Deficiency
Autoimmune Diseases
Bone Diseases
Bone Diseases, Metabolic
Calcium Metabolism Disorders
Connective Tissue Diseases
Deficiency Diseases
Immune System Diseases
Joint Diseases
Malnutrition
Metabolic Diseases
Musculoskeletal Diseases
Nutrition Disorders
Rheumatic Diseases
Ergocalciferols
Vitamin D
Bone Density Conservation Agents
Growth Substances
Micronutrients
Pharmacologic Actions
Physiological Effects of Drugs
Vitamins

ClinicalTrials.gov processed this record on September 01, 2015