Vitamin D Treatment, Pharmacogenetics and Glucose Metabolism
Condition: Polycystic Ovary Syndrome; Healthy; Vitamin D Deficiency
MeSH terms: Polycystic Ovary Syndrome; Vitamin D Deficiency
Study type: Interventional
Phase: Phase 4

Summary: 
      Background: Polycystic ovary syndrome (PCOS) is as common as 5-10% of all women in Austria.
      PCOS women frequently present with metabolic disturbances, hyperandrogenism and infertility.
      New therapy concepts are warranted. In our recent pilot study, vitamin D (vitD)
      supplementation significantly improved glucose metabolism and fertility. However, the
      efficacy of vitD administration shows individual variability indicating endogenous influences
      on pharmacological effects.

      A recent genome-wide association study reported three loci (DHCR7, CYP2R1, and GC) associated
      with vitD insufficiency. Moreover, vitD receptor (VDR) gene variants have already been known
      to be associated with insulin resistance.

      Aim: To test the hypothesis that vitD is efficient in changing metabolic parameters in PCOS
      and non-PCOS women longitudinally and to generate data on pharmacogenetic effects of vitD
      related genetic determinants adjusted for environmental factors.

      Primary outcome: Change from baseline in AUCgluc after vitD treatment. Secondary outcome: To
      generate the hypothesis that changes in metabolic and endocrine parameters following vitD
      treatment are associated with vitD related gene variants.

      Methods: 150 PCOS women with 25-hydroxyvitamin D (cholecalciferol, [25(OH)D]) levels <30
      ng/ml will be treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled
      trial over 24 weeks and investigated for metabolic and endocrine parameters as well as vitD
      related genetic variants. In addition, 150 non-PCOS women with 25(OH)D <30 ng/ml will be
      treated with vitD (20,000 IU/wk) or placebo in a 2:1 randomized controlled trial over 24
      weeks and investigated for metabolic and endocrine parameters as well as vitD related genetic
      variants. The response to vitD supplementation in both groups will be analysed according to
      genotype profiles.

      Significance: VitD might be a new therapeutic option without major side effects for PCOS
      patients. Exploring specific loci for pharmacogenetic vitD actions would open a new window
      for therapy modulation in PCOS and other metabolic diseases.
    


Intervention name(s): Vitamin D supplementation; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The treatment group will receive an oral dose of 20,000 IU vitD weekly (equivalent to 2857 IU/day) as oily drops (Oleovit D3-drops; producer: Fresenius Kabi Austria GmbH, Linz)
Other intervention name(s): A11CC05 Colecalciferol
Intervention MeSH terms: Vitamin D
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Polycystic Ovary Syndrome (PCOS); glucose metabolism; Vitamin D deficiency; vitamin D supplementation; pharmakogenetics; women