The Effect of Calcium and Vitamin D Supplements on Metabolic and Hormonal Disturbances in Polycystic Ovary Syndrome Patients

June 4, 2019 updated by: Damascus University

The Effect of Calcium and Vitamin D Supplements as an Adjuvant Therapy to Metformin on Metabolic and Hormonal Disturbances in Polycystic Ovary Syndrome Patients

The aim of this study is to investigate the safety and metabolic-hormonal efficiency of supplementation vitamin D deficient/insufficient PCOS women with (calcium +vitamin D + metformin) for 8 weeks compared to (placebo+ metformin).

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among females of reproductive age. The main manifestations of this syndrome are ovulatory dysfunction, hyperandrogenism, and polycystic ovarian morphology. Noticeably, PCOS is associated with several metabolic disturbances such as insulin resistance, compensatory hyperinsulinemia, dyslipidemia and central obesity, which increase the risk for long-term complications like type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases. Moreover, previous data demonstrated that, compared to normo-ovulatory women, PCOS patients might exhibit a dysregulation in the IGF system represented as an elevation in the serum levels of free Insulin-like growth factor-1 (IGF-1) and a reduction in the serum levels of Insulin-like growth factor binding protein-1 (IGFBP-1). However, the exact aetiology of PCOS remains unclear and current treatments are only moderately effective at controlling PCOS symptoms and preventing its complications. Growing evidence suggests a role of vitamin D in female reproductive diseases as the expression of Vitamin D Receptors (VDR) was identified in many organs throughout the female reproductive tract. On the top of that, vitamin D regulates over 300 genes, including genes that are important for glucose and lipid metabolism. Moreover, vitamin D deficiency is a common condition among women with PCOS, and several studies indicated an association between low levels of serum 25-hydroxyvitamin D (25-OH-Vitamin D) and manifestations of PCOS including insulin resistance, hyperandrogenism, and infertility. Further, a recent in-vitro study showed that vitamin D regulated steroidogenesis and IGFBP-1 production in cultured human ovarian cells, and many reports have suggested an interrelation between IGF-1 and vitamin D.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
40

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Syrian Arab Republic
      • Damascus, Syrian Arab Republic
        • Orient Hospital
      • Damascus, Syrian Arab Republic
        • Damascus University of Obstetrics and Gynecology Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 30 years (ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • PCOS women aged 18-30 years diagnosed according to the Rotterdam criteria.
  • Vitamin D deficiency or insufficiency according to the Endocrine Society Clinical Practice Guideline.
  • Normal liver function.
  • Normal kidney function.

Exclusion Criteria:

  • Pregnant, postpartum or breastfeeding women.
  • Females aged <18 or >30 years old.
  • Patients who were diagnosed with androgen-secreting tumours, Cushing's syndrome, congenital adrenal hyperplasia, hyperprolactinemia, hypercalcemia, malabsorption disorders, diabetes mellitus, thyroid disorders, liver disease, renal disease, epilepsy, cardiovascular disease.
  • History of kidney stones.
  • Usage of any hormonal therapy, corticosteroids (other than topical corticosteroids forms), insulin sensitizers, hypolipidemic agents, anti-obesity medications, vitamin D or calcium supplements, anti-epileptic drugs, or any other drugs known to affect endocrine parameters, carbohydrate metabolism, or calciotropic hormone concentrations during the last 3 months.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
PLACEBO_COMPARATOR: Metformin + Placebo
Drug: Metformin
Metformin (1500 mg/daily; the metformin dose was increased stepwise, starting with 500 mg once daily for the 1st week, 500 mg twice daily in the 2nd week, followed by 500 mg 3 times daily from the 3rd week onward). PO for 8 weeks.
Drug: Placebo
PO for 8 weeks.
EXPERIMENTAL: Calcium carbonate + Vitamin D3 + Metformin
Drug: Metformin
Metformin (1500 mg/daily; the metformin dose was increased stepwise, starting with 500 mg once daily for the 1st week, 500 mg twice daily in the 2nd week, followed by 500 mg 3 times daily from the 3rd week onward). PO for 8 weeks.
Dietary supplement: Vitamin D3
Vitamin D3 (Cholecalciferol) (6000 IU/daily). PO for 8 weeks.
Dietary supplement: Calcium Carbonate
Calcium carbonate (1000 mg/daily). PO for 8 weeks.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Change in quantitative insulin sensitivity check index (QUICKI).
Time Frame: baseline, 8 weeks weeks.
Assessment of QUICKI index at baseline and after 8 weeks of intervention.
baseline, 8 weeks weeks.
Change in Raynaud's index.
Time Frame: baseline, 8 weeks weeks.
Assessment of Raynaud's index at baseline and after 8 weeks of intervention.
baseline, 8 weeks weeks.
Change in McAuley Index.
Time Frame: baseline, 8 weeks weeks.
Assessment of McAuley Index at baseline and after 8 weeks of intervention.
baseline, 8 weeks weeks.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in glucose concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of glucose at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in insulin concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of insulin at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in homeostasis model assessment of insulin resistance index (HOMA-IR).
Time Frame: baseline, 8 weeks.
Assessment of HOMA-IR index at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in homeostasis model assessment of β-cell function index (HOMA-B).
Time Frame: baseline, 8 weeks.
Assessment of HOMA-B index at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in menstrual cycle abnormalities.
Time Frame: up to 8 weeks.
Assessment of menstrual cycles regularity (having normal menstrual cycle 21-35 days) was done at baseline and during the study period using a calendar by recording the time of the onset of the menstrual periods and the duration of menses.
up to 8 weeks.
Change in hirsutism score
Time Frame: baseline, 8 weeks.
Assessment of modified Ferriman-Gallwey score for hirsutism at baseline and after 8 weeks of intervention. (The score represents the hair growth in a male pattern on a woman shown in four different degrees of severity ( 0= no hair growth; 1= light hair growth; 2= moderate hair growth; 4= severe hair growth) in 9 different body parts; namely the upper lip, chin, chest, upper back, lower back, upper abdomen, lower abdomen, upper arms and thighs. The score is the sum of each region sub-score. Thus, it ranges between 0 and 36, where a score ≥ 6 was considered as a cut off Hirsutism).
baseline, 8 weeks.
Change in free testosterone concentration
Time Frame: baseline, 8 weeks.
Assessment of serum free testosterone concentration at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in serum concentration of follicle-stimulating hormone (FSH)
Time Frame: baseline, 8 weeks or the next spontaneous menstrual cycle depending on menstrual cycle status.
Assessment of serum concentration of FSH during the early follicular phase of menses at baseline and after 8 weeks of intervention if menstrual cycle regularity was reached during treatment period, or at baseline and the next spontaneous menstrual cycle after finishing the treatment if menstrual cycle regularity was not reached during treatment period.
baseline, 8 weeks or the next spontaneous menstrual cycle depending on menstrual cycle status.
Change in serum concentration of luteinizing hormone (LH) .
Time Frame: baseline, 8 weeks or the next spontaneous menstrual cycle depending on menstrual cycle status.
Assessment of serum concentration of LH during the early follicular phase of menses at baseline and after 8 weeks of intervention if menstrual cycle regularity was reached during treatment period, or at baseline and the next spontaneous menstrual cycle after finishing the treatment if menstrual cycle regularity was not reached during treatment period.
baseline, 8 weeks or the next spontaneous menstrual cycle depending on menstrual cycle status.
Change in serum concentration of Insulin-like growth factor-1 (IGF-1).
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of IGF-1 at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in serum concentration of Insulin-like growth factor binding protein-1 (IGFBP-1).
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of IGFBP-1 at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in IGF-1 to IGFBP-1 ratio.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of IGF-1 to IGFBP-1 ratio at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in lipid profile.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of total cholesterol (TC), high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglyceride (TG) and non-HDL cholesterol (non-HDL) at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in serum concentration of C-reactive protein (CRP)
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of CRP at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in Body mass index (BMI).
Time Frame: baseline, 8 weeks.
Assessment of weight and height in an overnight fasting status without shoes with light clothes at baseline and after 8 weeks of intervention. Weight and height will be combined to report BMI in kg/m^2.
baseline, 8 weeks.
Change in waist circumference.
Time Frame: baseline, 8 weeks.
Assessment of waist circumference in an overnight fasting status without shoes with light clothes at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in Hip circumference.
Time Frame: baseline, 8 weeks.
Assessment of Hip circumference in an overnight fasting status without shoes with light clothes at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in waist to hip ratio.
Time Frame: baseline, 8 weeks.
Assessment of waist to hip ratio in an overnight fasting status without shoes with light clothes at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in calcium concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of calcium at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in 25-OH-vitamin D concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of 25-OH-vitamin D at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in phosphorus concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of phosphorus at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in alanine transaminase (ALT) concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of ALT at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in aspartate transaminase (AST) concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of AST at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in urea concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of urea at baseline and after 8 weeks of intervention.
baseline, 8 weeks.
Change in creatinine concentration.
Time Frame: baseline, 8 weeks.
Assessment of serum concentration of creatinine at baseline and after 8 weeks of intervention.
baseline, 8 weeks.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Damascus University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
December 1, 2016

Primary Completion (ACTUAL)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2017

Study Completion (ACTUAL)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2017

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 18, 2018

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 3, 2019

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
January 4, 2019

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 6, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2018

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Ph-CT-2685

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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