Vitamin D Supplementation in Knee Osteoarthritis
Condition: Osteoarthritis, Knee; Vitamin D Supplementation
MeSH terms: Osteoarthritis; Osteoarthritis, Knee
Study type: Interventional

Summary: 
      Muscular (i.e., quadriceps) weakness is a major risk factor for predisposing the knee to
      osteoarthritis, impairing physical function, and increasing patient-reported pain. Muscular
      weakness is a consequence of and could contribute to the development of knee osteoarthritis.
      Minimizing muscular weakness has been fount to improve activities of daily living in patients
      with osteoarthritis symptoms. Although vitamin D associates with muscular strength in young
      and old populations, it is unknown if vitamin D supplementation improves muscular strength in
      subjects with osteoarthritis or osteoarthritis symptoms. It is also unknown if supplemental
      vitamin D alters circulating cytokine concentrations in subjects with knee osteoarthritis.
      Furthermore, it is probable that a more comprehensive supplement is necessary to improve
      muscular strength. Such as glucosamine sulfate and omega-3 fatty acids (i.e.,
      eicosapentaenoic and docosahexaenoic acids) which could be influential on knee pain and
      inflammation as well as muscular strength. Therefore, the purpose of this study is to
      identify the influence of vitamin D supplementation with and without glucosamine sulfate and
      omega-3 fatty acids on circulating cytokine concentrations and muscular strength in subjects
      with knee osteoarthritis symptoms. This study is intended to establish preliminary data
      identifying the influence of vitamin D supplementation on circulating cytokines and muscular
      strength in subjects with osteoarthritis at no more than minimal risk exposure to subjects.
    

Detailed description: 
      Knee osteoarthritis (OA) is a degenerative joint condition and a leading contributor to the
      global burden of disease. Estimates indicate that approximately 14 million people in the
      United States have symptomatic knee OA, and nearly half of those individuals are between 45
      and 65 years of age. Over the years, data have extended our knowledge regarding the early
      premise of knee OA being the sole consequence of "wear and tear" processes of articular
      cartilage and it is now recognized that knee OA arises, in part, as a consequence of
      cytokine-mediated cellular and signaling events.

      Cytokines are pleiotropic proteins instrumental to the immune response, host defenses, and
      intra- and inter-cellular signaling. Tumor necrosis factor (TNF)-α and interleukin (IL)-1β
      are pro-inflammatory cytokines that promote the catabolic and destructive events of knee OA
      in animal and human studies. These findings are corroborated by data illustrating
      chondrocytes as a site for pro-inflammatory cytokine production in knee OA, and that disease
      severity and progression associate with increasing TNF-α, IL-1β, and other cytokine
      concentrations in the circulation and transcriptional expression in peripheral blood
      leukocytes. Fortunately, IL-10 is an anti-inflammatory cytokine expressed in chondrocytes and
      possesses chondroprotective properties by inhibiting pro-inflammatory cytokine production.
      While some factors are unavoidable or unpreventable, such as aging, trauma, and genetic
      predisposition, disrupting the cytokine network could alter OA development and progression.

      Low circulating vitamin D concentrations are reported in elderly with and without knee
      osteoarthritis symptoms. Serum 25(OH)D concentrations associate with muscular strength or
      performance in elderly. Vitamin D supplementation increases serum 25(OH)D concentrations and
      improves muscular strength in elderly. Based on these observations, vitamin D is essential
      for muscle function in elderly, however, it is unknown if supplemental vitamin D influences
      muscular strength in subjects with knee OA. Furthermore, it is probable that a more
      comprehensive supplement is necessary to improve muscular strength.

      The aim of this study is to identify the influence of supplemental vitamin D on circulating
      cytokines and muscular strength in subjects with knee OA. This study consists of a
      double-blind, placebo-controlled experimental design. Subjects will be randomly assigned to
      one of three groups: (#1) vitamin D (cholecalciferol, 4000 IU) with glucosamine sulfate (1000
      mg) and omega-3 fatty acids (eicosapentaenoic (EPA, 580 mg) and docosahexaenoic (DHA, 470 mg)
      acids), (#2) vitamin D (cholecalciferol, 4000 IU) with matching glucosamine sulfate and
      omega-3 fatty acid placebo supplements, or (#3) matching vitamin D, glucosamine sulfate and
      omega-3 fatty acid placebo supplements. Supplements will be taken daily for 84 days (12
      weeks). Groups will be permutated in random blocks of six. Serum 25(OH)D, serum cytokines and
      muscular-based outcomes will be determined prior to, during, and following supplementation.
    

Intervention name(s): Placebo; Vitamin D (cholecalciferol); Glucosamine sulfate and omega-3 fatty acids
Intervention type(s): Dietary Supplement; Dietary Supplement; Dietary Supplement
Intervention description(s): Placebo supplement for vitamin D (cholecalciferol), glucosamine sulfate, and omega-3 fatty acids. Supplement was taken orally every day for 84-days.; Vitamin D (cholecalciferol). Supplement was taken orally every day for 84-days.; Glucosamine sulfate and omega-3 fatty acids supplement was taken orally every day for 84-days.
Intervention MeSH terms: Vitamin D; Cholecalciferol
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This study consists of a double-blind, placebo-controlled experimental design. Subjects will be randomly assigned to one of three groups: (#1) vitamin D (cholecalciferol, 4000 IU) with glucosamine sulfate (1000 mg) and omega-3 fatty acids (eicosapentaenoic (EPA, 580 mg) and docosahexaenoic (DHA, 470 mg) acids), (#2) vitamin D (cholecalciferol, 4000 IU) with matching glucosamine sulfate and omega-3 fatty acid placebo supplements, or (#3) matching vitamin D, glucosamine sulfate and omega-3 fatty acid placebo supplements. Supplements will be taken daily for 84 days (12 weeks). Groups will be permuted in random blocks of six.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment