A Randomized, Double-Blind, Placebo Controlled Trial to Evaluate the Effects of Vitamin D Supplementation on Metabolic and Fertility Parameters in PCOS Women
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 330
- 试验地点
- 1
- 主要终点
- Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 44 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •PCOS women:
- •25(OH)D levels below 30 ng/ml (measured at the baseline visit)
- •Polycystic ovary syndrome defined by the Androgen Excess Society (AES) criteria
- •Female, age of ≥ 18 and <45 years
- •BMI status: 75 PCOS women with BMI ≤25 kg/m² and 75 PCOS women with BMI>25 kg/m²
- •Written informed consent before study entry
- •Control women:
- •25(OH)D levels below 30 ng/ml (measured at the baseline visit)
- •Female, age of ≥ 18 and <45 years
- •BMI status: 75 nonPCOS women with BMI ≤25 kg/m² and 75 nonPCOS women with BMI>25 kg/m²
- •Written informed consent before study entry
排除标准
- •PCOS women:
- •Hypercalcemia defined as a serum calcium > 2,7 mmol/L
- •Pregnancy or lactating women
- •Disorders associated with androgen excess and/or menstrual irregularities apart from PCOS (thyroid dysfunction, hyperprolactinemia, adrenal hyperplasia, androgen secreting tumors)
- •Prevalent type 2 diabetes
- •Regular intake of vitD supplements at any time before study entry
- •Intake of medication influencing metabolic or endocrine parameters (insulin sensitizers, oral contraceptives, ...) in the last 3 months before study entry
- •Control women:
- •Hypercalcemia defined as a serum calcium > 2,7 mmol/L
- •Established PCOS or any of the AES criteria 29 (hyperandrogenism (clinical and/or biochemical), oligo- or anovulation, or polycystic ovaries on ultrasound)
- •Disorders associated with androgen excess and/or menstrual irregularities apart from PCOS (thyroid dysfunction, hyperprolactinemia, adrenal hyperplasia, androgen secreting tumors)
- •Prevalent type 2 diabetes
- •Pregnancy or lactating women
- •Regular intake of vitD supplements at any time before study entry
- •Intake of medication influencing metabolic or endocrine parameters (insulin sensitizers, oral contraceptives, ...) in the last 3 months before study entry
研究组 & 干预措施
Vitamin D supplementation
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)
干预措施: Vitamin D supplementation (Drug)
Placebo
the placebo group will receive oily drops without vitD
干预措施: Placebo (Drug)
结局指标
主要结局
Metabolic response during an oral glucose tolerance test (oGTT) as defined by AUCgluc
时间窗: Change from Baseline in AUC gluc at 24 weeks
次要结局
- Insulin sensitivity assessed by Quantitative Insulin-sensitivity Check Index (QUICKI)(Change from baseline in QUICKI at 24 weeks)
- HbA1c(Change from Baseline in HbA1c at 24 weeks)
- Testosterone(Change from Baseline in testosterone at 24 weeks)
- Menstrual frequency(Change from Baseline in menstrual frequency at 24 weeks)
- Free testosterone (FT)(Change from Baseline in FT at 4 weeks)
- Triglycerides(Change from Baseline in triglycerides at 24 weeks)
- Insulin resistance assessed by homeostatic model assessment-insulin resistance (HOMA-IR)(Change from Baseline in insulin resistance at 24 weeks)
- Lipid levels (total cholesterol)(Change from Baseline in total cholesterol at 24 weeks)
研究者
Lerchbaum Elisabeth, MD
A randomized, double-blind, placebo controlled trial to evaluate the effects of vitamin D
Medical University of Graz