Hypovitaminosis D, Polycystic Ovary Syndrome
Conditions
Keywords
Vitamin D, deficiency, hypovitaminosis D, Biodal, 25 hydroxy Vitamin D, 25hydroxyvitamin D, 25(OH)D, PCOS, insulin resistance, BMI, chromium levels, vitamin D 3, cholecalciferol, 50,000 IU
Brief summary
This is a prospective double-blind, randomized, parallel-group, placebo-controlled trial designed to examine the effect of supplementation with 50,000 IU vitamin D3 for 3 months on Polycystic Ovary Syndrome (PCOS) prognosis, serum 25-Hydroxy Vitamin D (25(OH)D) level, serum chromium level, insulin resistance, and Body Mass Index (BMI), in 60 overweight Jordanian female patients diagnosed with PCOS and with hypovitaminosis D.
Detailed description
This study is designed to assess the safety and efficacy of 50,000 IU vitamin D supplementation once weekly for 3 months on improvement in PCOS prognosis and improvement in serum 25(OH)D levels in 60 overweight Jordanian females (defined as having a BMI 25-30kg/m2), diagnosed with PCOS (based on Rotterdam criteria), and with hypovitaminosis D (defined as a serum 25(OH)D level \< 20 ng/mL), compared with placebo. Evaluation of the safety and efficacy of the dosing regimen will be conducted over 6 study visits during which clinical and biochemical signs of PCOS as well as serum 25(OH)D level, serum chromium level, insulin resistance, and BMI will be evaluated. The measurements will be collected as follows : day (-7) during screening , Day (0) base line measurements , Day (30) , Day(60), Day (90), day (104).
Interventions
DRUG50,000 IU vitamin D3
Film-coated tablet Biodal 50,000 IU containing cholecalciferol 50,000 IU
DRUGPlacebo
Placebo film-coated tablet of Biodal 50,000 IU
Sponsors
Jordan University of Science and Technology
Hayat Pharmaceutical Co. PLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 49 Years
Healthy volunteers
Yes
Inclusion criteria
* Female gender. * Aged between 18 and 49 years old. * Ethnic group (Caucasian, Middle-eastern). * Overweight (BMI 25-30 kg\^m2). * Diagnosed with Polycystic ovary syndrome according to Rotterdam criteria (Rotterdam SHRE-ASRM Sponsored Polycystic ovary syndrome consensus workshop group, 2004). * Diagnosed with hypovitaminosis D (serum 25(OH)D level \< 20 ng/mL). * Inadequate dietary intake of vitamin D (\<600 IU/day or \<15μg/day). * Physical examination being assessed and accepted by the attending physician. * Systolic blood pressure within the normal range (90-140 mmHg). * Diastolic blood pressure within the normal range (60-90 mmHg). * Heart rate within the normal range (60-100 BPM). * Oral body temperature within the normal range (35.9 - 37.6 Cᵒ). * Normal complete blood count , Liver Function enzymes test , Aspartate Transaminase (AST) , Alanine Transaminase (ALT) and Kidney function tests , Blood Urea Nitrogen (BUN) and Serum Creatinine (SrCr). * Participant is willing and able to give informed consent for participation in the study. * Able and willing to comply with all study requirements.
Exclusion criteria
* Female participants who are pregnant, lactating or planning pregnancy during the course of the study. * Ethnic group: non Caucasian. * Females aged \<18 or \>49 years old. * Underweight, normal body weight ,Body Mass Index (BMI) \< 25 kg\^m2 * Obese or morbidly obese (BMI \> 30 kg/m2) * Diagnosis with type 1 or type 2 diabetes mellitus, hypothyroidism, hyperthyroidism, liver disease, renal dysfunction, cardiovascular diseases, androgen-secreting tumor, Cushing syndrome, congenital adrenal hyperplasia, hyperprolactinemia, and/or virilism. * Known history or presence of food allergies or intolerance (e.g dairy products or gluten-containing foods), or any known condition that could interfere with the absorption, distribution, metabolism, or excretion of drugs. * History of drug or alcohol abuse, smoking of 10 cigarettes or more (or equivalent) per day. * Participants who took medications known to affect metabolic parameters, such as metformin and corticosteroid drugs, vitamin D and calcium. * Adequate dietary intake of vitamin D (600 IU/day or 15μg/day or more). * Participation in another clinical or bioequivalence study within 90 days prior to the start of this study period. * Participants with abnormal Electrocardiogram (ECG). * Participants with any abnormal laboratory results excluding \[ 25(OH)D, Creatinine (Cr), Calcium (Ca), phosphorus (PO4), C-reactive protein(CRP) , triglyceride , High Density Lipoprotien Cholesterol (HDL-C), Low Density Lipoprotien Cholesterol (LDL-C), total cholesterol (TC)/HDL-C ratio, fasting insulin , fasting blood glucose, oral glucose tolerance test, impaired glucose tolerance, Progesterone, total testosterone, sex hormone binding globulin, parathyroid hormone and free androgen index\].
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Ultrasound Examination of Number of Follicles and Ovarian Volume | 3 months | Evaluation of the efficacy of the dosing regimen as per the approved Summery of Product Characteristics (SmPC) (50,000 IU vitamin D3 once weekly for 3 months) on improvement in PCOS prognosis clinically using ultrasound examination. In this measure the reported results were the finding of the ultrasound examination after the course of the treatment /intervention as per the study protocol and reporting the numbers of patients with normal ovaries, One normal ovary and the other is polycystic or both ovaries are poly-cystic. An improvement in PCOS prognosis clinically by ultrasound examination is defined by: * decreasing the number of follicles to \< 12 follicles measuring 2-9 mm in diameter * decreasing ovarian volume to \< 10 cm3 |
| Menstrual Regularity | 3 months | Evaluation of the efficacy of the dosing regimen as per the approved SmPC (50,000 IU vitamin D3 once weekly for 3 months) on improvement in PCOS prognosis by assessment of menstrual regularity An improvement in PCOS prognosis by assessment of menstrual regularity is measured through improving progesterone level \> 4 ng/mL. One of the clinical signs of improving PCOS prognosis is menstrual cycle regularity. In this measure ,the reported results consist of the number of volunteers/patients in each arm either with regular menstrual cycle or irregular menstrual cycle after completing the course of the treatment/ intervention as per the study protocol. The results will be statistically analyzed using paired student t-test and 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated. |
| Hirsutism Score | 3 months | The scale ranges between 0 and 36, where A score of 8 or higher was considered as androgen excess (Ferriman and Gallwey, 1961).Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on PCOS prognosis by evaluating Hirsutism Score.Hirsutism score was assessed using self-administrated Ferriman-Gallwey scoring system (Ferriman and Gallwey, 1961). Each participant answered the hirsutism test with the help of a trained nurse who was working in the same clinic. The score of each body site may range between 0 (no excessive terminal hair growth) to 4 (extensive terminal hair growth). In this measure , the hirsutism score were reported in each are after completing the course of treatment/ intervention as per the study protocol. after which, the means were compared for statistical significance between the two groups / arms. |
| Serum Progesterone Level | 3 months | The results below show the Serum Progesterone level after treatment in each arm after completing the course of the treatment / intervention as per the study protocol.after which, the means were compared for statistical significance between the two groups / arms. After which, the means were compared for statistical significance between the two groups / arms. The evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on PCOS Prognosis by measuring Change in Serum Progesterone level. One of the clinical signs of improving PCOS prognosis is the change in progesterone level. the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated. |
| Total Testosterone Level | 3 months | Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on PCOS Prognosis by measuring Change in Total Testosterone level before and after the treatment. In this measure , the Total Testosterone levels in each arm were reported after completing the course of the treatment / intervention as per the study protocol. One of the clinical signs of improving PCOS prognosis is the change in testosterone level. After which, the means were compared for statistical significance between the two groups / arms. the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated. |
| Free Androgen Index | 3 months | Free Androgen Index is calculated as the ratio of total testosterone to sex hormone binding globulin (SHBG). In this measure , the Free Androgen Index in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms. Improvement assessment of PCOS Prognosis by evaluating the change in Free Androgen Index. One of the clinical signs of improving PCOS prognosis is the change in FAI. the results will be statistically analyzed using Wilcoxon (Mann- Whitney) method at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated. |
| Sex Hormone Binding Globulin Concentration | 3 months | Evaluation of Biodal 50,000 IU on improvement of PCOS Prognosis by comparing the Sex Hormone Binding Globulin concentrations in both groups/arms. One of the clinical signs of improving PCOS prognosis is the change in the Sex Hormone Binding Globulin Concentration. In this measure , the Sex Hormone Binding Globulin Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms. The results will be statistically analyzed using Wilcoxon (Mann-Whiteny) method at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serum 25-Hydroxy Vitamin D3 Level | 3 months | Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on increase the level of serum 25(OH)D \> 20 ng/ml by measuring of the serum 25(OH)D levels on 104 of the study period after 3 months treatment . In this measure , Serum 25-Hydroxy Vitamin D3 leveln in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms. |
| Serum C-Reactive Protien Concentration | 3 months | Evaluation of the Efficacy of the Dose (50,000IU) and the Dose Regimen on inflammation by measuring reduction of the serum concentration of C-Reactive Protein before and after the treatment. In this measure , Serum C-Reactive Protien Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms. |
| Serum Chromium Concentration | 3 months | Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on improving serum chromium level to be \> 0.05 and \< 0.5 ppm. which will be assessed by measuring serum chromium level before and after supplementation of Vitamin D3. In this measure , Serum chromium Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms. One of the clinical signs of improving PCOS prognosis is the improvement in serum chromium level . the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated. |
| Serum Glucose Concentration in Oral Glucose Tolerance Test 1st hr After Treatment | 3 months | Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on reduction of insulin resistance and improving insulin sensitivity measuring Oral Glucose Tolerance Test 1st hr after the treatment and to compare with same at baseline point within the time frame. In this measure , Serum Glucose Concentration in Oral Glucose Tolerance test in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms. One of the clinical signs of improving PCOS prognosis is the improvement in insulin resistance by evaluating the results of Oral Glucose Tolerance Test 1st hr . the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI). |
| Body Mass Index | 3 months | Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on reduction of body mass index to be \<25-30 kg/m\^2. Evaluation of the Effectiveness of the dose (50,000IU) and the dose regimen as per the approved SmPC on reduction in Body Mass Index before and after the treatment. After which, the means were compared for statistical significance between the two groups / arms. In this measure , Body Mass Index in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). |
| Serum Parathyroid Hormone Concentration | 3 months | Evaluation of the Safety of the Dose and the Dose Regimen as Per the SmPC by measuring the change in the level of serum Serum Parathyroid Hormone (PTH) Concentration before and after the treatment and/or reporting any adverse events through the trial period. In this measure , Serum Parathyroid Hormone Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms. |
| Serum Calcium Concentration | 3 months | Evaluation of the safety of the dose and the dose regimen as per the SmPC by measuring the change in the level of serum Calcium before and after the treatment and/or reporting it as adverse. event through the trial period. as the increase of Serum calcium concentration above the normal level is considered as adverse event for the intervention dose regimen of this study for the purpose of evaluating the safety. In this measure , Serum Calcium Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms. |
| Serum Phosphorous Concentration | 3 months | Evaluation of the safety of the dose and the dose regimen as per the SmPC by measuring the change in the level of serum PO4 Concentration before and after the treatment and/or reporting as adverse event through the trial period.as the increase of Serum phosphoruse concentration above the normal level is considered as adverse event for the intervention dose regimen of this study for the purpose of evaluating the safety. In this measure , Serum Phosphorous Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms. |
Countries
Jordan
Participant flow
Recruitment details
Random sample of women attending outpatient obstetrics and gynecology clinics in King Abdullah Hospital / Jordan University of Science and Technology
Pre-assignment details
Approximately 120 women will be assessed for eligibility clinically, anthropometrically, dietary and biochemically. Women diagnosed with PCOS and vitamin D deficiency will be randomly divided into 2 groups
Participants by arm
| Arm | Count |
|---|---|
| Vitamin D3 (Biodal 50,000IU) 50,000 IU vitamin D3 (Biodal 50,000IU) coated tablets by oral route
50,000IU Vitamin D3: 50,000IU Vitamin D3 (Biodal 50,000IU ) once weekly for 3 months | 29 |
| Placebo (Biodal 50,000IU Placebo) Placebo (Biodal 50,000IU Placebo tablets) coated tablets by oral route
Placebo: 50,000IU Vitamin D3 placebo (Biodal 50,000IU placebo) once weekly for 3 months | 29 |
| Total | 58 |
Baseline characteristics
| Characteristic | Total | Placebo (Biodal 50,000IU Placebo) | Vitamin D3 (Biodal 50,000IU) |
|---|---|---|---|
| 25(OH)D Serum Level | 12.415 ng/ml STANDARD_DEVIATION 3.08 | 12.37 ng/ml STANDARD_DEVIATION 2.91 | 12.46 ng/ml STANDARD_DEVIATION 3.29 |
| Age, Continuous Age | 23.56 years | 23.56 years | 23.56 years |
| Body Mass Index | 27.33 kg/m^2 STANDARD_DEVIATION 0.23 | 27.33 kg/m^2 STANDARD_DEVIATION 0.3 | 27.33 kg/m^2 STANDARD_DEVIATION 0.16 |
| Calcium Serum Level | 2.3 mmol/L STANDARD_DEVIATION 0.02 | 2.3 mmol/L STANDARD_DEVIATION 0.02 | 2.3 mmol/L STANDARD_DEVIATION 0.02 |
| Chromium Serum Level | 0.295 ppm STANDARD_DEVIATION 0.01 | 0.30 ppm STANDARD_DEVIATION 0.01 | 0.29 ppm STANDARD_DEVIATION 0.01 |
| C-Reactive Protien Serum Level | 5.15 mg/L STANDARD_DEVIATION 0.91 | 3.7 mg/L STANDARD_DEVIATION 0.69 | 6.6 mg/L STANDARD_DEVIATION 1.13 |
| Fasting Blood Sugar Serum Level | 4.83 mmol/L STANDARD_DEVIATION 0.04 | 4.9 mmol/L STANDARD_DEVIATION 0.07 | 4.7 mmol/L STANDARD_DEVIATION 0.07 |
| Fasting Insulin Serum Level | 10.0 uU/ml STANDARD_DEVIATION 3.4 | 9.8 uU/ml STANDARD_DEVIATION 2.17 | 10.2 uU/ml STANDARD_DEVIATION 1.23 |
| Hirsutism Score | 16.65 units on a scale STANDARD_DEVIATION 1.025 | 16.8 units on a scale STANDARD_DEVIATION 1.19 | 16.5 units on a scale STANDARD_DEVIATION 0.86 |
| Lipid Profile HDL | 1.3 mmol/L STANDARD_DEVIATION 0.05 | 1.3 mmol/L STANDARD_DEVIATION 0.04 | 1.3 mmol/L STANDARD_DEVIATION 0.06 |
| Lipid Profile LDLC | 3.35 mmol/L STANDARD_DEVIATION 0.17 | 3.4 mmol/L STANDARD_DEVIATION 0.19 | 3.3 mmol/L STANDARD_DEVIATION 0.15 |
| Lipid Profile Total Cholestrol | 5.3 mmol/L STANDARD_DEVIATION 0.23 | 5.3 mmol/L STANDARD_DEVIATION 0.26 | 5.3 mmol/L STANDARD_DEVIATION 0.2 |
| Menstrual Cycle Regularity Irrigular | 51 participants | 25 participants | 26 participants |
| Menstrual Cycle Regularity Regular | 7 participants | 4 participants | 3 participants |
| Oral Glucose Tolerance Test (1st Hour) | 7.55 mmol/L STANDARD_DEVIATION 0.41 | 7.7 mmol/L STANDARD_DEVIATION 0.48 | 7.4 mmol/L STANDARD_DEVIATION 0.33 |
| Parathyroide Hormon Serum Level | 63.55 Pg/ml STANDARD_DEVIATION 5.225 | 61.8 Pg/ml STANDARD_DEVIATION 4.54 | 65.3 Pg/ml STANDARD_DEVIATION 5.91 |
| Phosphorus Serum Level | 1.1 nmol/L STANDARD_DEVIATION 0.03 | 1.1 nmol/L STANDARD_DEVIATION 0.02 | 1.1 nmol/L STANDARD_DEVIATION 0.03 |
| Progesterone Serum Level | 7.7 nmol/L STANDARD_DEVIATION 2.67 | 10.7 nmol/L STANDARD_DEVIATION 3.48 | 5.2 nmol/L STANDARD_DEVIATION 1.86 |
| Region of Enrollment Jordan | 58 participants | 29 participants | 29 participants |
| Sex: Female, Male Female | 58 Participants | 29 Participants | 29 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Sex Hormon Binding Globulin | 84.55 nmol/L STANDARD_DEVIATION 13 | 111.2 nmol/L STANDARD_DEVIATION 16.7 | 57.9 nmol/L STANDARD_DEVIATION 9.29 |
| TC / HDL-C Ratio | 4.4 Ratio STANDARD_DEVIATION 0.23 | 4.5 Ratio STANDARD_DEVIATION 0.26 | 4.3 Ratio STANDARD_DEVIATION 0.2 |
| Total Testosteron Serum Level | 1.95 nmol/L STANDARD_DEVIATION 0.16 | 1.8 nmol/L STANDARD_DEVIATION 0.15 | 2.1 nmol/L STANDARD_DEVIATION 0.17 |
| Ultrasound Examination Both are Polycystic | 58 participants | 29 participants | 29 participants |
| Ultrasound Examination Both Overies are Normal | 0 participants | 0 participants | 0 participants |
| Ultrasound Examination Left or Right is Normal | 0 participants | 0 participants | 0 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 1 / 30 | 1 / 30 |
| serious Total, serious adverse events | 0 / 30 | 0 / 30 |
Outcome results
Primary
Free Androgen Index
Free Androgen Index is calculated as the ratio of total testosterone to sex hormone binding globulin (SHBG). In this measure , the Free Androgen Index in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms. Improvement assessment of PCOS Prognosis by evaluating the change in Free Androgen Index. One of the clinical signs of improving PCOS prognosis is the change in FAI. the results will be statistically analyzed using Wilcoxon (Mann- Whitney) method at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Free Androgen Index | 4.5 Ratio | Standard Deviation 0.93 |
| Placebo | Free Androgen Index | 4.4 Ratio | Standard Deviation 1.1 |
p-value: 0.04Wilcoxon (Mann-Whitney)
Primary
Hirsutism Score
The scale ranges between 0 and 36, where A score of 8 or higher was considered as androgen excess (Ferriman and Gallwey, 1961).Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on PCOS prognosis by evaluating Hirsutism Score.Hirsutism score was assessed using self-administrated Ferriman-Gallwey scoring system (Ferriman and Gallwey, 1961). Each participant answered the hirsutism test with the help of a trained nurse who was working in the same clinic. The score of each body site may range between 0 (no excessive terminal hair growth) to 4 (extensive terminal hair growth). In this measure , the hirsutism score were reported in each are after completing the course of treatment/ intervention as per the study protocol. after which, the means were compared for statistical significance between the two groups / arms.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Hirsutism Score | 11.5 units on a scale | Standard Error 0.93 |
| Placebo | Hirsutism Score | 16.7 units on a scale | Standard Error 1.21 |
p-value: 0.01t-test, 2 sided
Primary
Menstrual Regularity
Evaluation of the efficacy of the dosing regimen as per the approved SmPC (50,000 IU vitamin D3 once weekly for 3 months) on improvement in PCOS prognosis by assessment of menstrual regularity An improvement in PCOS prognosis by assessment of menstrual regularity is measured through improving progesterone level \> 4 ng/mL. One of the clinical signs of improving PCOS prognosis is menstrual cycle regularity. In this measure ,the reported results consist of the number of volunteers/patients in each arm either with regular menstrual cycle or irregular menstrual cycle after completing the course of the treatment/ intervention as per the study protocol. The results will be statistically analyzed using paired student t-test and 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated.
Time frame: 3 months
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Menstrual Regularity | Regular | 27 participants |
| Vitamin D3 (Biodal 50,000IU) | Menstrual Regularity | Irregular | 2 participants |
| Placebo | Menstrual Regularity | Regular | 4 participants |
| Placebo | Menstrual Regularity | Irregular | 25 participants |
p-value: 0.001Chi-squared
Primary
Serum Progesterone Level
The results below show the Serum Progesterone level after treatment in each arm after completing the course of the treatment / intervention as per the study protocol.after which, the means were compared for statistical significance between the two groups / arms. After which, the means were compared for statistical significance between the two groups / arms. The evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on PCOS Prognosis by measuring Change in Serum Progesterone level. One of the clinical signs of improving PCOS prognosis is the change in progesterone level. the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum Progesterone Level | 5.8 nmol/L | Standard Error 1.86 |
| Placebo | Serum Progesterone Level | 7.3 nmol/L | Standard Error 2.42 |
p-value: 0.65t-test, 2 sided
Primary
Sex Hormone Binding Globulin Concentration
Evaluation of Biodal 50,000 IU on improvement of PCOS Prognosis by comparing the Sex Hormone Binding Globulin concentrations in both groups/arms. One of the clinical signs of improving PCOS prognosis is the change in the Sex Hormone Binding Globulin Concentration. In this measure , the Sex Hormone Binding Globulin Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms. The results will be statistically analyzed using Wilcoxon (Mann-Whiteny) method at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Sex Hormone Binding Globulin Concentration | 85.9 nmol/L | Standard Deviation 15.19 |
| Placebo | Sex Hormone Binding Globulin Concentration | 100.6 nmol/L | Standard Deviation 15.8 |
p-value: 0.02Wilcoxon (Mann-Whitney)
Primary
Total Testosterone Level
Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on PCOS Prognosis by measuring Change in Total Testosterone level before and after the treatment. In this measure , the Total Testosterone levels in each arm were reported after completing the course of the treatment / intervention as per the study protocol. One of the clinical signs of improving PCOS prognosis is the change in testosterone level. After which, the means were compared for statistical significance between the two groups / arms. the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Total Testosterone Level | 1.6 nmol/L | Standard Deviation 0.17 |
| Placebo | Total Testosterone Level | 1.9 nmol/L | Standard Deviation 0.1 |
p-value: 0.25t-test, 2 sided
Primary
Ultrasound Examination of Number of Follicles and Ovarian Volume
Evaluation of the efficacy of the dosing regimen as per the approved Summery of Product Characteristics (SmPC) (50,000 IU vitamin D3 once weekly for 3 months) on improvement in PCOS prognosis clinically using ultrasound examination. In this measure the reported results were the finding of the ultrasound examination after the course of the treatment /intervention as per the study protocol and reporting the numbers of patients with normal ovaries, One normal ovary and the other is polycystic or both ovaries are poly-cystic. An improvement in PCOS prognosis clinically by ultrasound examination is defined by: * decreasing the number of follicles to \< 12 follicles measuring 2-9 mm in diameter * decreasing ovarian volume to \< 10 cm3
Time frame: 3 months
Population: The participants in the treatment and placebo groups will be classified into two categories of prognosis (improved and not improved) and will be analyzed using Chi-square test, if Chi-square is higher than 3.84 (df=1) it will be statistically significant (p-value\</= 0.05)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Ultrasound Examination of Number of Follicles and Ovarian Volume | Both Normal | 7 participants |
| Vitamin D3 (Biodal 50,000IU) | Ultrasound Examination of Number of Follicles and Ovarian Volume | Left or Right Normal | 5 participants |
| Vitamin D3 (Biodal 50,000IU) | Ultrasound Examination of Number of Follicles and Ovarian Volume | Both Polycystic | 17 participants |
| Placebo | Ultrasound Examination of Number of Follicles and Ovarian Volume | Both Polycystic | 18 participants |
| Placebo | Ultrasound Examination of Number of Follicles and Ovarian Volume | Both Normal | 0 participants |
| Placebo | Ultrasound Examination of Number of Follicles and Ovarian Volume | Left or Right Normal | 11 participants |
Comparison: The participants in the treatment and placebo groups will be classified into two categories of prognosis (improved and not improved) and will be analyzed using Chi-square test, if Chi-square is higher than 3.84 (df=1) it will be statistically significant (p-value\</= 0.05)p-value: 0.001Chi-squared
Secondary
Body Mass Index
Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on reduction of body mass index to be \<25-30 kg/m\^2. Evaluation of the Effectiveness of the dose (50,000IU) and the dose regimen as per the approved SmPC on reduction in Body Mass Index before and after the treatment. After which, the means were compared for statistical significance between the two groups / arms. In this measure , Body Mass Index in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Body Mass Index | 25.6 kg/m^2 | Standard Error 0.37 |
| Placebo | Body Mass Index | 26.5 kg/m^2 | Standard Error 0.37 |
p-value: 0.08t-test, 2 sided
Secondary
Serum 25-Hydroxy Vitamin D3 Level
Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on increase the level of serum 25(OH)D \> 20 ng/ml by measuring of the serum 25(OH)D levels on 104 of the study period after 3 months treatment . In this measure , Serum 25-Hydroxy Vitamin D3 leveln in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum 25-Hydroxy Vitamin D3 Level | 48.2 ng/ml | Standard Error 2.03 |
| Placebo | Serum 25-Hydroxy Vitamin D3 Level | 11.8 ng/ml | Standard Error 0.76 |
Comparison: Both arms where evaluated at which paired t-test for the mean difference in the two arm was calculated . where the serum 25-OH Vit D3 was measured at 0 day time and after the end of the study. after that a paired t-test where applied for the difference for the 25-OH VitD3 levels between the two time pointsp-value: <0t-test, 2 sided
Secondary
Serum Calcium Concentration
Evaluation of the safety of the dose and the dose regimen as per the SmPC by measuring the change in the level of serum Calcium before and after the treatment and/or reporting it as adverse. event through the trial period. as the increase of Serum calcium concentration above the normal level is considered as adverse event for the intervention dose regimen of this study for the purpose of evaluating the safety. In this measure , Serum Calcium Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum Calcium Concentration | 2.3 mmol/L | Standard Error 0.02 |
| Placebo | Serum Calcium Concentration | 2.3 mmol/L | Standard Error 0.2 |
p-value: 0.89t-test, 2 sided
Secondary
Serum Chromium Concentration
Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on improving serum chromium level to be \> 0.05 and \< 0.5 ppm. which will be assessed by measuring serum chromium level before and after supplementation of Vitamin D3. In this measure , Serum chromium Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol. After which, the means were compared for statistical significance between the two groups / arms. One of the clinical signs of improving PCOS prognosis is the improvement in serum chromium level . the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI) for the difference of the means within and between the two groups will be calculated.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum Chromium Concentration | 0.27 ppm | Standard Error 0.01 |
| Placebo | Serum Chromium Concentration | 0.27 ppm | Standard Error 0.01 |
p-value: 0.67t-test, 2 sided
Secondary
Serum C-Reactive Protien Concentration
Evaluation of the Efficacy of the Dose (50,000IU) and the Dose Regimen on inflammation by measuring reduction of the serum concentration of C-Reactive Protein before and after the treatment. In this measure , Serum C-Reactive Protien Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum C-Reactive Protien Concentration | 5.4 mg/L | Standard Error 1.06 |
| Placebo | Serum C-Reactive Protien Concentration | 3.9 mg/L | Standard Error 1.17 |
p-value: 0.35t-test, 2 sided
Secondary
Serum Glucose Concentration in Oral Glucose Tolerance Test 1st hr After Treatment
Evaluation of the Efficacy of the dose (50,000IU) and the dose regimen as per the approved SmPC on reduction of insulin resistance and improving insulin sensitivity measuring Oral Glucose Tolerance Test 1st hr after the treatment and to compare with same at baseline point within the time frame. In this measure , Serum Glucose Concentration in Oral Glucose Tolerance test in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms. One of the clinical signs of improving PCOS prognosis is the improvement in insulin resistance by evaluating the results of Oral Glucose Tolerance Test 1st hr . the results will be statistically analyzed using paired student t-test at 95% confidence interval (CI).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum Glucose Concentration in Oral Glucose Tolerance Test 1st hr After Treatment | 6.9 mmol/L | Standard Error 0.5 |
| Placebo | Serum Glucose Concentration in Oral Glucose Tolerance Test 1st hr After Treatment | 6.4 mmol/L | Standard Error 0.54 |
p-value: 0.51t-test, 2 sided
Secondary
Serum Parathyroid Hormone Concentration
Evaluation of the Safety of the Dose and the Dose Regimen as Per the SmPC by measuring the change in the level of serum Serum Parathyroid Hormone (PTH) Concentration before and after the treatment and/or reporting any adverse events through the trial period. In this measure , Serum Parathyroid Hormone Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum Parathyroid Hormone Concentration | 39.1 Pg/ml | Standard Error 2.6 |
| Placebo | Serum Parathyroid Hormone Concentration | 52.6 Pg/ml | Standard Error 4.18 |
p-value: 0.01t-test, 2 sided
Secondary
Serum Phosphorous Concentration
Evaluation of the safety of the dose and the dose regimen as per the SmPC by measuring the change in the level of serum PO4 Concentration before and after the treatment and/or reporting as adverse event through the trial period.as the increase of Serum phosphoruse concentration above the normal level is considered as adverse event for the intervention dose regimen of this study for the purpose of evaluating the safety. In this measure , Serum Phosphorous Concentration in each arm were reported after completing the course of the treatment / intervention as per the study protocol (Treatment with either Biodal or Placebo for 3 months). After which, the means were compared for statistical significance between the two groups / arms.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Vitamin D3 (Biodal 50,000IU) | Serum Phosphorous Concentration | 1.2 mmol/L | Standard Error 0.3 |
| Placebo | Serum Phosphorous Concentration | 1.2 mmol/L | Standard Error 0.2 |
p-value: 0.6t-test, 2 sided