Vitamin D, Chronic Kidney Disease (CKD) and the Microcirculation
Condition: Chronic Kidney Disease; Vitamin D Deficiency
MeSH terms: Kidney Diseases; Renal Insufficiency, Chronic; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      Overall research aims: This study will examine the effect of vitamin D supplementation on the
      function of the endothelium and microcirculation of patients with chronic kidney disease and
      vitamin D deficiency.

      Hypothesis: Vitamin D therapy in patients with CKD and concomitant vitamin D deficiency will
      improve endothelial, and therefore microcirculatory function, reduce levels of oxidative
      stress and thus reduce the risk of future CVS events in this population.
    

Detailed description: 
      Research rationale: Cardiovascular (CVS) diseases are the major cause of death in patients
      with chronic kidney disease (CKD), accounting for approximately half of all deaths. Patients
      with CKD are far more likely to die of CVS disease than progress to end stage renal disease.
      Recently, vitamin D deficiency has been identified as a non-traditional CVS risk factor.
      However, vitamin D is not routinely prescribed in the early stages of CKD.

      Previous publications have established that endothelial, and therefore, microcirculatory
      dysfunction is a marker of CVS health and a predictor of future CVS events. Studies have also
      shown that clinical assessments of the microcirculation reflect the overall health and
      function of the endothelium. Vitamin D has been shown to improve endothelial function in
      diabetic patients with vitamin D deficiency and normal kidney function. However, no study has
      examined endothelial dysfunction in patients with CKD and vitamin D deficiency.

      With the prevalence of CKD and concomitant vitamin D deficiency increasing worldwide, there
      is a pressing need to examine the effects of vitamin D therapy in the early stages of CKD.
      This study involves the use of four, non-invasive, detailed assessments of the
      microcirculation which could be used in a clinical setting to enhance CVS risk profiling. The
      current study design includes novel clinical and in vitro work examining endothelial
      function, oxidative stress levels and potential cellular mechanisms by which vitamin D
      improves endothelial function. Early detection of endothelial dysfunction, before end stage
      renal disease is reached, will provide a powerful tool for predicting future CVS events and
      thus provide an opportunity to intervene with therapies, including vitamin D, at an early
      stage of renal dysfunction.

      Study objectives: Primary study objective - to evaluate the effects of vitamin D therapy on
      endothelial function in patients with CKD and vitamin D deficiency. Secondary study
      objective: to evaluate the effects of vitamin D therapy on key clinical parameters in
      patients with CKD and vitamin D deficiency.

      Research plan: We will conduct a double blind, randomised control trial comparing oral
      ergocalciferol to a placebo in adult, non-diabetic patients with CKD stages 3-4 and vitamin D
      deficiency (defined as < 10ng/ml (<30nmol/L)). Based on power calculations, 40 subjects will
      be recruited in each arm as well as 15 healthy control subjects. Subjects will be followed
      for 7 months in total.
    

Intervention name(s): Ergocalciferol (Vitamin D); Placebo
Intervention type(s): Drug; Drug
Intervention description(s): ergocalciferol: 50,000 IU per week for 1 month followed by 50,000 IU per month for 5 months.; Matching placebo at same dose schedule as ergocalciferol
Other intervention name(s): Drisdol
Intervention MeSH terms: Vitamin D; Ergocalciferols
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment