Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary Syndrome Patients and Healthy Women (CNP)
Primary Purpose
Polycystic Ovary Syndrome, c Type Natriuretic Peptide, Menstrual Irregularity
Status
Completed
Phase
Not Applicable
Locations
Cyprus
Study Type
Interventional
Intervention
C type natriuretic peptide
Sponsored by
About this trial
This is an interventional diagnostic trial for Polycystic Ovary Syndrome focused on measuring c type natriuretic peptide, polycystic ovary syndrome, menstrual cycle
Eligibility Criteria
Inclusion Criteria:
- PCOS defined according to Rotterdam criteria
- Healthy normal menstruating women
Exclusion Criteria:
- Diabetes mellitus
- Cardiavascular disease
- Renal disease
- Any drug usage
- Smoking
- Pregnancy
Sites / Locations
- Near East University Faculty of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
women with polycystic ovary syndrome
Healthy women of reproductive age
Arm Description
36 patients with PCOS
30 patients with regular normal menstrual cycle
Outcomes
Primary Outcome Measures
Serum CNP Levels of PCOS and Healthy Participants
The comparison of serum levels of C type natriuretic peptide among PCOS and healthy women
Roc Curve of CNP
We made a cut off value estimation for the diagnosis of PCOS by serum CNP levels using Receiver operator characteristics. The ROC curve incorporates both sensitivity (true positive rate) and specificity (true negative rate) providing a single assessment incorporating both measures. The higher the total area under the curve, the greater the predictive power of the CNP for diagnosing PCOS
Secondary Outcome Measures
Comparison of FSH and LH of PCOS and Healthy Women
Serum FSH and LH of PCOS and healthy women were compared
Serum Estradiol Levels of PCOS and Healthy Women
Serum Estradiol levels of PCOS and Healthy Women were compared
Serum Tiroid Stimulating Hormone of PCOS and Healthy Women
serum tiroid stimulating hormone of PCOS and healthy women were compared
Serum Prolactin Levels of PCOS and Healthy Women
serum prolactin levels of PCOS and healthy women were compared
Serum Androstenedione Levels of PCOS and Healthy Women
Serum Androstenedione Levels of PCOS and Healthy Women were compared
Serum Dehydroepiandrosterone Sulfate (DHEAS) Levels of PCOS and Healthy Women
Serum dehydroepiandrosterone sulfate (DHEAS) Levels of PCOS and Healthy Women were compared
Serum Total Testosterone Levels of PCOS and Healthy Women
Serum Total Testosterone Levels of PCOS and Healthy Women were compared
Serum Free Testosterone Levels of PCOS and Healthy Women
Serum Free Testosterone Levels of PCOS and Healthy Women were compared
Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women
Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women were compared
Free Androgen Index of Participants
Free androgen index of participants were compared. It was calculated with the formula 100XTotal testosterone/Sex hormone binding globulin
Serum Glucose, Total Cholesterol and Triglycerides Levels of Participants
Serum glucose, total cholesterol and triglycerides levels of participants were compared
High Density Lipoprotein and Low Density Lipoprotein Levels of Participants
High density lipoprotein and low density lipoprotein levels of participants were compared
Serum Insulin Levels of Participants
Serum Insulin Levels of Participants were compared
Homeostatic Model Assessment of Insulin Resistance of Participants
homeostatic model assessment of insulin resistance of participants were compared. The calculation was made with formula Glucose X Insulin/405.
Full Information
NCT ID
NCT04006171
First Posted
June 29, 2019
Last Updated
October 7, 2021
Sponsor
Near East University, Turkey
1. Study Identification
Unique Protocol Identification Number
NCT04006171
Brief Title
Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary Syndrome Patients and Healthy Women
Acronym
CNP
Official Title
C Type Natriuretic Peptide and Polycystic Ovary Syndrome
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
July 15, 2019 (Actual)
Primary Completion Date
September 1, 2020 (Actual)
Study Completion Date
September 1, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Near East University, Turkey
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
5. Study Description
Brief Summary
Recent studies have shown that C natriuretic peptide is produced from granulosa cells, increasing cumulative guanosine monophosphate (cGMP) production by affecting cumulus cells through natriuretic peptide receptors. It is suggested that produced cGMP maintains the transport of oocytes via the gap junctions and leads to a continuous increase in cyclic adenosine monophosphate (cAMP) levels in the oocyte. An important role of increased internal cAMP levels in the oocyte is shown to suppress meiotic progression.
Deoxyribonucleic acid studies in animals have shown that expression of the natriuretic peptide precursor increases during the periovulatory period and shows that this increase decreases rapidly after luteinizing hormone / human chorionic gonadotropin (hCG) stimulation.Human studies have shown that after ovulation induction, the CNP level in follicular fluid decreases following ovulatory dose of hCG.Polycystic ovary syndrome (PCOS) is the most common endocrine disease in the reproductive period, characterized by hyperandrogenism, oligo-anovulation, and polycystic ovarian morphology on ultrasonography, and in an animal study investigating the relationship between CNP and PCOS, serum CNP levels were increased in polycystic ovary syndrome.CNP serum level is thought to show differences between healthy women and women with polycystic ovary syndrome.
Detailed Description
In this prospective study, a total of 60 patients are planed to be included. PCOS group will be consisted of 30 women and control group will include 30 healthy women with regular menstruation aged between 18-40 years old. PCOS diagnosis will be made according to Rotterdam criteria.
Age and body mass index of all participants will be recorded. BMI will be calculated by dividing weight by height in square meters. Then morning fasting venous blood samples will be taken from the patients between 2nd-5th day of menstruation for both groups. All blood samples will be centrifuged on the day of collection. Sera will be aliquoted into 1.5 mL Eppendorf (Eppendorf, Milano, Italy) tubes, and will be kept at -80°C until the day of CNP test. For the PCOS patients describing oligo/anovulation, after excluding pregnancy, progesterone withdrawal bleeding will be created and then the patients will be evaluated. Serum levels of LH, FSH, estradiol, thyroid stimulating hormone (TSH), prolactin (PRL), androstenedione, dehydroepiandrosterone sulfate (DHEAS), total testosterone, free testosterone, sex hormone binding globulin (SHBG), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), glucose and insulin levels will be analyzed. For insulin sensitivity, homeostatic model of insulin resistance (HOMA-IR) will be used and it will be calculated by the formula: HOMA-IR ¼ fasting blood glucose (mg/dL)fasting insulin (mIU/mL)/405. Free androgen index will be calculated by the formula 100x (Total testosteron/SHBG).
Serum CNP levels of the patients will be analyzed by an enzyme-linked immunosorbent (ELISA) assay for human C-type natriuretic peptide in accordance with the manufacturer's instructions (SEA721Hu, ELISA Kit for Human C-Type Natriuretic Peptide, Wuhan USCN Business Co., Ltd., Cloud-Clone Corp., CCC, USA).
Data will be analyzed using Statistical Packege for Social Sciences software (SPSS v15, SPSS Inc, Chicago, IL, USA). Independent t-test will be used to compare the parameters with normal distribution. Parameters that don't fulfill the parametric test assumptions will be compared using Mann-Whitney U test. Correlation of CNP with other parameters will be analyzed using Spearman's rank correlation test. Receiver operating characteristic (ROC) curve will be used to evaluate diagnostic sensitivity and specificity of CNP for PCOS. P values less than 0.05 will be regarded as statistically significant.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Polycystic Ovary Syndrome, c Type Natriuretic Peptide, Menstrual Irregularity, Hyperandrogenism
Keywords
c type natriuretic peptide, polycystic ovary syndrome, menstrual cycle
7. Study Design
Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
90 (Actual)
8. Arms, Groups, and Interventions
Arm Title
women with polycystic ovary syndrome
Arm Type
Active Comparator
Arm Description
36 patients with PCOS
Arm Title
Healthy women of reproductive age
Arm Type
Active Comparator
Arm Description
30 patients with regular normal menstrual cycle
Intervention Type
Diagnostic Test
Intervention Name(s)
C type natriuretic peptide
Intervention Description
Serum level of CNP in PCOS and healthy women
Primary Outcome Measure Information:
Title
Serum CNP Levels of PCOS and Healthy Participants
Description
The comparison of serum levels of C type natriuretic peptide among PCOS and healthy women
Time Frame
Second or Third Day of Menstruation
Title
Roc Curve of CNP
Description
We made a cut off value estimation for the diagnosis of PCOS by serum CNP levels using Receiver operator characteristics. The ROC curve incorporates both sensitivity (true positive rate) and specificity (true negative rate) providing a single assessment incorporating both measures. The higher the total area under the curve, the greater the predictive power of the CNP for diagnosing PCOS
Time Frame
Second or Third Day of Menstruation
Secondary Outcome Measure Information:
Title
Comparison of FSH and LH of PCOS and Healthy Women
Description
Serum FSH and LH of PCOS and healthy women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Estradiol Levels of PCOS and Healthy Women
Description
Serum Estradiol levels of PCOS and Healthy Women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Tiroid Stimulating Hormone of PCOS and Healthy Women
Description
serum tiroid stimulating hormone of PCOS and healthy women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Prolactin Levels of PCOS and Healthy Women
Description
serum prolactin levels of PCOS and healthy women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Androstenedione Levels of PCOS and Healthy Women
Description
Serum Androstenedione Levels of PCOS and Healthy Women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Dehydroepiandrosterone Sulfate (DHEAS) Levels of PCOS and Healthy Women
Description
Serum dehydroepiandrosterone sulfate (DHEAS) Levels of PCOS and Healthy Women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Total Testosterone Levels of PCOS and Healthy Women
Description
Serum Total Testosterone Levels of PCOS and Healthy Women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Free Testosterone Levels of PCOS and Healthy Women
Description
Serum Free Testosterone Levels of PCOS and Healthy Women were compared
Time Frame
Second or Third Day of Menstruation
Title
Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women
Description
Serum Sex Hormone Binding Globulin Levels of PCOS and Healthy Women were compared
Time Frame
Second or Third Day of Menstruation
Title
Free Androgen Index of Participants
Description
Free androgen index of participants were compared. It was calculated with the formula 100XTotal testosterone/Sex hormone binding globulin
Time Frame
Second or Third Day of Menstruation
Title
Serum Glucose, Total Cholesterol and Triglycerides Levels of Participants
Description
Serum glucose, total cholesterol and triglycerides levels of participants were compared
Time Frame
Second or third day of menstruation and morning fasting
Title
High Density Lipoprotein and Low Density Lipoprotein Levels of Participants
Description
High density lipoprotein and low density lipoprotein levels of participants were compared
Time Frame
Second or Third Day of Menstruation-morning fasting
Title
Serum Insulin Levels of Participants
Description
Serum Insulin Levels of Participants were compared
Time Frame
Second or Third Day of Menstruation-morning fasting
Title
Homeostatic Model Assessment of Insulin Resistance of Participants
Description
homeostatic model assessment of insulin resistance of participants were compared. The calculation was made with formula Glucose X Insulin/405.
Time Frame
Second or Third Day of Menstruation-morning fasting
10. Eligibility
Sex
Female
Gender Based
Yes
Gender Eligibility Description
women
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
PCOS defined according to Rotterdam criteria
Healthy normal menstruating women
Exclusion Criteria:
Diabetes mellitus
Cardiavascular disease
Renal disease
Any drug usage
Smoking
Pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Özay
Organizational Affiliation
Near East University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Near East University Faculty of Medicine
City
Nicosia
ZIP/Postal Code
99138
Country
Cyprus
12. IPD Sharing Statement
Plan to Share IPD
No
Citations:
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20947764
Citation
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Kawamura K, Cheng Y, Kawamura N, Takae S, Okada A, Kawagoe Y, Mulders S, Terada Y, Hsueh AJ. Pre-ovulatory LH/hCG surge decreases C-type natriuretic peptide secretion by ovarian granulosa cells to promote meiotic resumption of pre-ovulatory oocytes. Hum Reprod. 2011 Nov;26(11):3094-101. doi: 10.1093/humrep/der282. Epub 2011 Aug 23.
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Comparison of Serum C Type Natriuretic Peptide Levels Between Polycystic Ovary Syndrome Patients and Healthy Women
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