A Multicentre, Phase-II, Randomised, Double Blind, Placebo-controlled Study to Assess the Safety and the Efficacy of a Weekly Administered Dose of 30,000 IU Vitamin D (Colecalciferol) in Deficient Patients Diagnosed With PCOS
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 115
- 试验地点
- 8
- 主要终点
- Recovery of ovarian function
研究概览
简要总结
This is a human, II/b phase, multicentre, randomised, double blind, placebo-controlled study to assess the safety and the efficacy of a weekly administered dose of 30,000 IU vitamin D (colecalciferol) in deficient patients diagnosed with PCOS.
Investigational products: 30.000 IU vitamin D or placebo administered once a week for 12-weeks-long period, followed by a 12-week-long open label treatment 30.000 IU vitamin D in a follow-up period.
Each participant should be checked for regular dietary Ca intake and to assure the optimal calcium level the supplementation is provided with a commercially available Citrocalcium 200 mg tablets.
Setting:
I. Baseline and screening period:
Baseline period considered as when the exogenous Vitamin D intake should not exceed the level of 1000 IU intake per day or a total 5000 NE per week dosages applied (in forms of any Vitamin D3 medication or multivitamin products) at least for 30 days prior the assessment made.
II. Double-blind treatment period:
Once a week per os applied Vitamin D or placebo treatment for 12 weeks according to randomisation of trial subjects in a 1:1 assignment. By the end of this period an interim assessment will be performed based on the analysis of primary efficacy parameters, stratification to responder and non-responder groups.
III. Open label and follow-up phase:
An open-label 30000 IU of Vitamin D treatment on weekly basis. (Vitamin D3 Pharma Patent 30000 IU tablets) for additional 12 weeks and continue with the follow-up assessments. A compassionate use of patient diary for additional 26 weeks.
Objectives:
Primary objectives: to assess the efficacy as a recovery of ovarian function based on progesterone levels and menses diary in at least 20% of trial subjects, compared to placebo treated group Secondary Objectives: assess the efficacy and safety of orally administered vitamin D treatment by the changes in 25(OH) D levels in PCOS patients.
Explore the changes in Ovarian-morphology based on the results of standard TVUS Imaging: detection of adverse drug reactions during treatment periods, by frequency and distribution compared to follow-up periods and placebo group.
Anticipated participants: 168
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 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Female subject age >18 years.
- •Clinical and/or biochemical hyperandrogenism and the proven PCOS by the "Rotterdam" criteria, (ovarian dysfunction, oligo- and/or anovulation, and the morphology of polycystic ovaries on ultrasound images when other etiologies are excluded)
- •25(OH)D levels are between 10-28 ng/ml by inclusion
- •Subject can not be under any kind of ongoing hormone or metformin therapies and no indication that requires continuation
- •Has the ability and willingness to understand and comply with study procedures and to give written informed consent prior to enrollment in the study or initiation of study procedures
- •Study subject has the ability and willingness to understand and comply with study procedures and to give written informed consent prior to enrollment in the study or initiation of study procedures
排除标准
- •Has been exposed to any investigational agent within 3 month of enrolment to the study
- •Sever metabolic disease on endocrine disease in etiology different from PCOS
- •Significant obesity (BMI> 36)
- •Any other signs of lab results that may lead to other etiologies in differentiation, or menopause
- •Increased serum calcium level results or symptoms of hypercalcemia in last one year
- •Hypercalciuria or kidney stone appearance in last one year
- •Sever kidney diseases (CKD 3 or higher)
- •Chronic or serious disease, which can significantly influence the absorption, metabolism of vitamin D or Ca
- •Heart failure or angina pectoris,
- •More than 1000 IU vitamin D per day intake or in total >5000 IU per week within 1 month prior to trial (in any forms medication, or nutritional food supplement). The patient is not under hormonal therapy for ovulation stimulation purposes and was not involved in two months prior the study
- •The patient is under hormonal therapy for the aim of ovulation stimulation or was involved in within 3 months prior the study
- •Existence or suspected gravidity
- •Any other finding or symptoms which are by the opinion of the Investigator may indicate a potential interference with the safety of participating trial subjects
- •Has a known hypersensitivity to any of the investigational drug or vehicle components.
- •Concomitant medication which is not allowed:
- •glycosides
- •metformin
- •magnesium-containing preparations (antacids)
- •cholestyramine and other ion exchange resins, orlistat
- •thiazide diuretics
- •regular use of microsomal enzyme inducers (anticonvulsants, sedatives, etc.).
- •corticosteroids (except for dermatological use)
- •products containing phosphorus
- •regular use of laxatives (such as paraffin oil)
- •fat absorption inhibitory drugs
- •any kind of hormone therapy (including therapeutic use of birth control pills, within 2 months prior inclusion) except treatment of stabile hypothyroidism
研究组 & 干预措施
Cholecalciferol
Cholecalciferol 30,000IU weekly orally
干预措施: Cholecalciferol (Drug)
Placebo
Placebo tablets weekly orally
干预措施: Placebo (Drug)
结局指标
主要结局
Recovery of ovarian function
时间窗: Up to 32 weeks, continuously
Recovery of ovarian function is detected by changes in progesterone levels (lutal phase progesterone level reaches 2 ng/ml)
次要结局
- 25(OH)D levels(Up to 32 weeks)
- Change in hemoglobin A1c level(Up to 32 weeks)
- Length of menstrual cycle(Up to 32 weeks)
- Incidence of adverse events(Up to 32 weeks, continuously)
- Change in urinary calcium/creatinine ratio(Up to 32 weeks)
- Change in fasting glucose level(Up to 32 weeks)
- Change in ovarian morphology(Up to 32 weeks)
- Variation in menstrual cycles length(Up to 32 weeks)
- Change in serum calcium level(Up to 32 weeks, continuously)
研究者
Istvan Takacs
M.D., DSc., Director of Department
Semmelweis University