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Trial record 3 of 3 for:    18596274 [PUBMED-IDS]

Is There Association Between Vitamin D Levels And Insulin Resistance In Polycystic Ovary Syndrome?

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ClinicalTrials.gov Identifier: NCT02803476
Recruitment Status : Unknown
Verified June 2016 by Sara Saad Youssef Morsi, Ain Shams Maternity Hospital.
Recruitment status was:  Recruiting
First Posted : June 17, 2016
Last Update Posted : June 17, 2016
Sponsor:
Information provided by (Responsible Party):
Sara Saad Youssef Morsi, Ain Shams Maternity Hospital

Tracking Information
First Submitted Date June 10, 2016
First Posted Date June 17, 2016
Last Update Posted Date June 17, 2016
Study Start Date March 2016
Estimated Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 16, 2016)
Quantitative Insulin Sensitivity Check Index (QUICKI) [ Time Frame: After sample collection and analysis, through study completion, an average of 20 weeks. ]
A validated measure of Insulin sensitivity based on fasting Insulin (uIU/mL) and Glucose (mg/dL).
Original Primary Outcome Measures Same as current
Change History No Changes Posted
Current Secondary Outcome Measures
 (submitted: June 16, 2016)
  • Fasting Plasma Insulin [ Time Frame: 12 hours of fasting. ]
    Overnight fasting venous samples
  • Fasting Plasma Glucose [ Time Frame: 12 hours of fasting. ]
    Overnight fasting venous samples.
  • Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) [ Time Frame: After sample collection and analysis, through study completion, an average of 20 weeks. ]
    A validated measure of Insulin sensitivity based on fasting Insulin (uIU/mL) and Glucose (mg/dl)
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title Is There Association Between Vitamin D Levels And Insulin Resistance In Polycystic Ovary Syndrome?
Official Title Is There An Association Between Vitamin D Levels And Insulin Resistance In Polycystic Ovary Syndrome?
Brief Summary

The primary aim of the current study is to clarify whether serum vitamin D levels [25(OH)D3] have a temporal association with insulin resistance and/or insulin sensitivity in PCOS women versus healthy ones.

To achieve this aim, the investigators will conduct a prospective observational study involving obese and lean PCOS women in comparison to obese and lean healthy subjects living in Cairo, Egypt.

Detailed Description

Polycystic ovary syndrome (PCOS) is the most common gynecological endocrinopathy among women of reproductive age. The prevalence of PCOS among such women is estimated to be 6.4% to 6.8% worldwide. PCOS is a heterogeneous androgen excess disorder with different degrees of reproductive and metabolic dysfunctions.

There are many considerations to explain the complexity of the underlying pathogenesis of PCOS, particularly the well-known roles of hypothalamic-pituitary gonadal dysfunctions, metabolic abnormalities and genetic factors, the developmental model of chronic diseases postulates that early-life events affect the individual differences in vulnerability to lifestyle and environment, suggesting that hostile intrauterine environment and low birth weight may predispose to the development of early adrenarche, PCOS and metabolic syndrome later in life; however, the definite pathogenesis and real underlying etiologies of PCOS remain uncertain and ripe with opportunities for further research.

PCOS is the most common cause of anovulatory infertility, and its foremost clinical symptoms include anovulation or oligo-ovulation, infertility, menstrual irregularity, polycystic ovaries, and hyperandrogenism in women without specific underlying diseases of the adrenal or pituitary glands. A primary abnormality in folliculogenesis may have played a role in the development of PCOS. The polycystic ovaries contain multiple antral follicles, some of which prematurely acquire LH receptors and become responsive to LH, increasing granulosa cell proliferation in the preantral follicles, resulting in anovulation. PCOS is defined by the presence of having at least 2 of the following criteria: irregular or absent ovulation, elevated levels of androgenic hormones, and enlarged ovaries containing at least 12 follicles each.

Several epidemiological and interventional PCOS studies demonstrate that serum vitamin D concentrations are inversely associated with fasting plasma glucose levels, insulin resistance, body mass index (BMI), and body fat contributing to the pathogenesis of PCOS by promoting insulin resistance and affecting glucose metabolism in PCOS women. Vitamin D is either produced in the skin in response to direct exposure to sunlight from dehydrocholesterol or obtained from the diet. Vitamin D3 (cholecalciferol) is converted into 25-hydroxyvitamin D3 principally in the liver and 1,25-dihydroxyvitamin D3 in the kidney by two hydroxylation steps. 1,25-dihydroxyvitamin D3 is an active form of vitamin D, it binds to vitamin D receptors (VDRs) that are expressed in 2776 genomic positions and modulate the expression of 229 genes in more than 30 different tissues, such as the skeleton, pancreatic islet cells, parathyroid glands, and ovaries.

About 3% of the human genome are regulated by VDRs gene including those responsible for glucose and fat metabolism as well as blood regulation; it's active form acts through its VDRs either directly or through regulation of intercellular calcium that facilitates insulin secretion. It has been suggested that Vitamin D increases insulin sensitivity through the effect on its muscle cell receptors by increasing insulin receptors or increasing the insulin sensitivity of insulin receptors to insulin. Also, being a fat soluble vitamin, a higher proportion of vitamin D may be sequestered in the adipose tissue of obese individuals, resulting in lower 25-(OH)D3 concentration levels; therefore, a low vitamin D status is suspected to be a risk factor for impaired glucose tolerance, insulin resistance and a substantial cause of obesity.

In the light of the literature, the relationship between vitamin D status and insulin or glucose metabolism has been investigated in women with PCOS who are vitamin D deficient, although there is no consensus on whether or not serum vitamin D levels are different in women with or without PCOS. Vitamin D level is defined as a serum level of 25-hydroxycholecalciferol [25-(OH)D3]. Vitamin D insufficiency is defined as a 25-(OH)D3 concentration of <30ng/ml and frank vitamin D deficiency is defined as a 25-(OH)D3 concentration of <20ng/ml. There appears to be a growing disconnect between the observational studies and the randomized clinical trials of vitamin D supplementation in PCOS women with insulin resistance and glucose intolerance. Observational studies keep showing a fairly consistent relationship between low concentration levels of vitamin D and insulin resistance or glucose intolerance, while almost all randomized trials, including a meta-analysis of vitamin D supplementation on women suffering from PCOS shows minimal, if any, benefit in terms of correcting insulin resistance or increasing insulin sensitivity indexes or an improvement in glucose metabolism. The results published indicated that the change was not significant and did not show any difference in insulin resistance which is the core patho-physiology of this syndrome.

Vitamin D deficiency (VDD) is common in women with and without PCOS and may be associated with metabolic and endocrine disorders in PCOS. However, the phenotypic manifestation of PCOS is associated with various degrees of gonadotropic and/or metabolic abnormalities and there has been much debate as to whether it represents a single disorder or several that can only be determined by the interaction of multiple genetic and environmental factors. Previously conducted prospective observational studies that investigated the temporal relationship between VDD and metabolic disturbances (resistance to the action of insulin and glucose intolerance) in PCOS are lacking. If VDD were causally related to PCOS and the subsequent development of metabolic dysfunction in PCOS, then further prospective observational studies with repeated VDD assessment and better characterization of PCOS disease severity at enrollment are needed to clarify whether VDD is a co-determinant of metabolic dysregulations in PCOS compared to Non-PCOS women (controls).

Study design:

A prospective observational study which will be conducted in the outpatient clinics of Ain Shams University Women's Hospital after being approved by the local ethical committee.

Sample size justification:

For sample size determination, the investigators used the following formula: N= 2 x K x [SD/μ1-μ2]2 where N equals the number of patients per arm and K is constant (K=7.9) setting the type-1 error α at 0.5 and the power β at 80%. Results from a previous study calculated the mean (standard deviation (SD)) of vitamin Din the PCOS group(μ1)is 15.45 ± 7.88 ng/ml and in the control group(μ2) 12.83 ± 5.76ng/ml. Anticipating a 10% drop out rate, we calculated that a sample size of 83 subjects in each group, with a total of 166 subjects is enough to detect a significant difference, if any existed.

Objectives:

  1. To measure plasma concentrations of vitamin D, fasting glucose, fasting Insulin, androgen levels, FSH and LH levels in all participants diagnosed with PCOS and healthy participants.
  2. To clarify whether VDD is a co-determinant of metabolic dysregulations particularly insulin resistance and glucose metabolism in PCOS when compared to healthy women (controls).
  3. To develop a better assessment of the PCOS severity and factors involved.

Methodology:

All of the recruited subjects will undergo:

  • Written consent.
  • Complete history with particular emphasis on menstrual, sexual, gynecological, medical as (Irregular cycles, oligomenorrhea, polymenorrhea, secondary amenorrhea, dysmenorrhea primary or secondary infertility, cancer, thyroid disease, galactorrhea, hirsutism, pelvic pain...etc), previous pelvic surgeries, induction of ovulation, vaginal infection, abnormal Pap smears, life style habits such as alcohol and smoking.
  • Physical examination including general examination, Anthropometric measurements like weight (in kg), height (in meters), Body Mass Index (BMI), waist to hip ratio (WHR), Waist circumference (midway between the lowest rib margin and iliac crest) and hip circumference (over the widest part of the gluteal region). Signs of androgen excess, thyroid toxicity, and galactorrhea will be examined. Patients will undergo gynecological ultrasound in the follicular phase and to assess the ovarian size and morphology. Local examination to exclude uterine abnormalities, cervical tenderness, masses, vaginal infections and discharge.
  • Diagnostic tests: Overnight fasting venous blood samples will be withdrawn between the 2nd and 3rd day of menstruation, and withdrawal bleeding following progesterone therapy for 5 days in amenorheic women, centrifuged and frozen to -80 C until analyzed for the assessment of vitamin D levels, Androgen levels, plasma Glucose and plasma Insulin, FSH and LH analogues.

All collected data will be tabulated and statistically analyzed.

Statistical analysis:

Descriptive statistics for measured variables will be expressed as range, mean and standard deviation (for metric data); range, median and interquartile range (for discrete data); and number and proportions (for categorical data).

Demographic data, primary and secondary outcomes of all women will be compared using t-test (for quantitative parametric measures), Mann-Whitney's U-test (for quantitative non-parametric measures) and chi-squared for Fisher's Exact tests (for categorical measures). Pearson's correlation coefficient (for metric variables) and Spearman's correlation coefficient (for rank variables) will be used to estimate association between variables. Microsoft Excel and SPSS for Windows will be used for data presentation and statistical analysis.

Ethical considerations:

The clinical research study will be conducted in accordance with the above mentioned design, safety and reporting of cases matching the relevant policies, requirements, and regulations of the Ethical Committee of the Department of Obstetrics and Gynecology - Faculty of Medicine, Ain Shams University Women's Hospital.

Consent procedure:

The investigator will make certain that an appropriate informed consent process is in place to ensure that potential research subjects, or their authorized representatives, are fully informed about the nature and objectives of the clinical study, the benefits of study participation and their rights as research subjects. The investigator will obtain a written, signed informed consent of each subject, or the subject's authorized representative, prior to performing any study-specific procedures on the subject. The investigator will retain the original signed informed consent form.

Subject confidentiality:

All evaluation forms, reports and other records that leave the site will not include unique personal data to maintain subject confidentiality.

Study Type Observational
Study Design Observational Model: Case Control
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples Without DNA
Description:
Overnight fasting venous blood samples will be withdrawn between the 2nd and 3rd day of menstruation, and withdrawal bleeding following progesterone therapy for 5 days in amenorheic women, centrifuged and frozen to -80 C until analyzed for the assessment of vitamin D levels, Androgen levels, plasma Glucose and plasma Insulin, FSH and LH analogues.
Sampling Method Non-Probability Sample
Study Population In this study, a total of 166 consenting women with and without PCOS will be asked to participate and divided into two groups; 83 female patients will represent PCOS recruited from the outpatient clinics of Ain Shams university maternity hospital, along with 83 non-PCOS women who will represent controls recruited after fulfilling specific criteria.
Condition
  • Polycystic Ovary Syndrome
  • Insulin Resistance
  • Vitamin D Deficiency
Intervention Not Provided
Study Groups/Cohorts
  • Cases
    Polycystic ovary syndrome (PCOS) female patients. 20-35 years of age.
  • Controls
    Non-PCOs female subjects. 20-35 years of age.
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Unknown status
Estimated Enrollment
 (submitted: June 16, 2016)
166
Original Estimated Enrollment Same as current
Estimated Study Completion Date August 2016
Estimated Primary Completion Date July 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria

PCOS female patients criteria:

Inclusion Criteria:

  • PCOS will be diagnosed in accordance with Rotterdam criteria.
  • No relevant systemic diseases e.g. hypertension, DM.

Exclusion Criteria:

  • Androgen secreting tumor.
  • Cushing syndrome.
  • Congenital adrenal hyperplasia.
  • Hyperprolactinemia.
  • Virilism.
  • Pregnant or nursing.
  • Conditions known to affect Vitamin D deficiency like renal disease, liver disease, gastrointestinal problems and malnutrition.
  • Taking vitamin D or calcium supplements.
  • Untreated hypothyroidism or hyperthyroidism.

Non-PCOS female subjects criteria:

  • Regular menstrual cycles
  • Not suffering from any conditions known to affect Vitamin D deficiency like renal disease, liver disease, gastro-Intestinal problems and malnutrition.
  • Not taking vitamin D or calcium supplements.
  • No relevant systemic diseases e.g. hypertension, DM.
Sex/Gender
Sexes Eligible for Study: Female
Ages 20 Years to 35 Years   (Adult)
Accepts Healthy Volunteers Yes
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Egypt
Removed Location Countries  
 
Administrative Information
NCT Number NCT02803476
Other Study ID Numbers 2732016
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: Yes
Responsible Party Sara Saad Youssef Morsi, Ain Shams Maternity Hospital
Study Sponsor Ain Shams Maternity Hospital
Collaborators Not Provided
Investigators
Study Chair: Hisham M Fathi, Phd , MD Professor of Obstetrics & Gynecology. Faculty of Medicine - Ain Shams University.
Study Director: Sherif A Ashoush, Phd, MD Professor of Obstetrics & Gynecology. Faculty of Medicine - Ain Shams University.
Principal Investigator: Sara S Youssef, MD MD, Obstetrics and Gynecology. Faculty of Medicine - Ain Shams University
PRS Account Ain Shams Maternity Hospital
Verification Date June 2016