The Effect of Vitamin D Supplementation Among Overweight Jordanian Women With Polycystic Ovary Syndrome (PCOS)

NCT02328404 | Completed Phase 3 Results DMC

• 2 other identifiers: VitD31.02013-003353-22
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Polycystic Ovary Syndrome; Hypovitaminosis D

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

Outcome Measures

Primary Outcomes (7)

• 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

  3 months

• 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.

  3 months

• 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.

  3 months

• 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.

  3 months

• 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.

  3 months

• 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.

  3 months

• 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.

  3 months

Secondary Outcomes (8)

• Serum 25-Hydroxy Vitamin D3 Level

  3 months

• Serum Chromium Concentration

  3 months

• Serum Glucose Concentration in Oral Glucose Tolerance Test 1st hr After Treatment

  3 months

• Body Mass Index

  3 months

• Serum Parathyroid Hormone Concentration

  3 months

Study Arms (2)

vitamin D3 (Biodal 50,000 IU)

ACTIVE COMPARATOR

50,000 IU Vitamin D3 tablet given orally once weekly for 3 months

Drug: 50,000 IU vitamin D3

placebo

PLACEBO COMPARATOR

Placebo tablet given orally once weekly for 3 months

Drug: Placebo

Interventions

50,000 IU vitamin D3 DRUG

Film-coated tablet Biodal 50,000 IU containing cholecalciferol 50,000 IU

Also known as: Biodal 50,000 IU, cholecalciferol 50,000 IU

vitamin D3 (Biodal 50,000 IU)

Placebo DRUG

Placebo film-coated tablet of Biodal 50,000 IU

Also known as: Biodal 50,000IU

placebo

Eligibility Criteria

• Age: 18 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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 \[ 25(OH)D, Creatinine (Cr), Calcium (Ca), phosphorus (PO4), C-reactive protein(CRP) , triglyceride , High Density Lipoprotien Cholesterol (HDL-C), Low Density Lipoprotien Cholesterol (LDL-C), total cholesterol (TC)/HDL-C ratio, fasting insulin , fasting blood glucose, oral glucose tolerance test, impaired glucose tolerance, Progesterone, total testosterone, sex hormone binding globulin, parathyroid hormone and free androgen index\].

Sponsors & Collaborators

• Hayat Pharmaceutical Co. PLC: lead
• Jordan University of Science and Technology: collaborator

Study Sites (1)

King Abdullah University Hospital

Irbid, Irbid Governorate, 22110, Jordan

Location

Related Publications (1)

• Al-Bayyari N, Al-Domi H, Zayed F, Hailat R, Eaton A. Androgens and hirsutism score of overweight women with polycystic ovary syndrome improved after vitamin D treatment: A randomized placebo controlled clinical trial. Clin Nutr. 2021 Mar;40(3):870-878. doi: 10.1016/j.clnu.2020.09.024. Epub 2020 Sep 24.

  PMID: 33010974 DERIVED

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Vitamin D Deficiency; Insulin Resistance

Interventions

Cholecalciferol

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases; Avitaminosis; Deficiency Diseases; Malnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases

Intervention Hierarchy (Ancestors)

Cholestenes; Cholestanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Sterols; Vitamin D; Secosteroids; Membrane Lipids; Lipids

Limitations and Caveats

* The study was conducted only in the north of Jordan * Body composition was measured by bioelectrical impedance * Insulin resistance was assessed using the indirect method of assessment (HOMA) * The study was done exclusively on overweight women

Results Point of Contact

• Title: DR. ALA' ABU RUQA'A
• Organization: Hayat Pharmaceutical industries

tbd@hayatpharma.com

00962 6 4162607

Study Officials

• ALA M ABU RUQAA, MSC PHARM

  HAYAT PHARMACEUTICAL INDUSTRIES CO. PLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 14, 2014
• First Posted: December 31, 2014
• Study Start: February 1, 2014
• Primary Completion: September 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 4, 2016
• Results First Posted: April 17, 2015

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

JO (1)