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
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
115
30,000IU cholecalciferol
Placebo tablets
Semmelweis University - Departement Medicine and Oncology
Budapest, Hungary
MediMOM Healthy Center
Budapest, Hungary
Róbert Károly Hospital
Budapest, Hungary
Gynpraxis Nőgyógyászat
Debrecen, Hungary
Somogy County Kaposi Mór Teaching Hospital
Kaposvár, Hungary
Borsod-Abaúj-Zemplén County Hospital
Miskolc, Hungary
SZTE-ÁOK - 1st Dept. of Internal MEdicine
Szeged, Hungary
Gynofarm Outpatient Clinic
Székesfehérvár, Hungary
Recovery of ovarian function
Recovery of ovarian function is detected by changes in progesterone levels (lutal phase progesterone level reaches 2 ng/ml)
Time frame: Up to 32 weeks, continuously
Length of menstrual cycle
Determined by patient reported number of days between two menstrual cycles
Time frame: Up to 32 weeks
Variation in menstrual cycles length
Determined by patient reported menstrual cycle length and regularity, measured in days
Time frame: Up to 32 weeks
Incidence of adverse events
Incidence of adverse events (safety and tolerability), evaluated at every visit
Time frame: Up to 32 weeks, continuously
Change in serum calcium level
Change in serum calcium levels in mmol/l (safety measure), evaluated every clinical visit
Time frame: Up to 32 weeks, continuously
Change in urinary calcium/creatinine ratio
Change in urinary calcium/creatinine ratio (\[mmol/l\]/\[umol/l\]) (safety measure), evaluated every clinical visit
Time frame: Up to 32 weeks
25(OH)D levels
Evaluation of treatment of changes in 25(OH)D blood levels compared between treatment groups
Time frame: Up to 32 weeks
Change in fasting glucose level
Change in fasting glucose level (mmol/l), measured at every visit
Time frame: Up to 32 weeks
Change in hemoglobin A1c level
Change in hemoglobin A1c level (IFCC validated, mmol/mol), measured every 12 weeks
Time frame: Up to 32 weeks
Change in ovarian morphology
Changes in ovarian follicle count assessed by TVUS and evaluated by the Rotterdam criteria (having 12 or more follicles, measuring between 2 and 9 mm)
Time frame: Up to 32 weeks
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