Serum CNP LevelsCONCT04000815
Serum Levels of C Type Natriuretic Peptide in Different Reproductive Periods
A study testing C Type Natriüretic Peptide in people with Serum CNP Levels and Healthy Reproductive Age Women, run by Near East University, Turkey at 1 site in Cyprus.
Trial summary
Recent studies have shown that C natriuretic peptide (CNP) is produced from granulosa cells, increasing cumulative guanosine monophosphate (cGMP) production by affecting cumulus cells through natriuretic peptide receptors.It has been suggested that the transport of cGMP to oocyte via gap junctions causes a continuous… Read more about this study
- Who is it for?
- Ages 18 to 70 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Serum CNP Levels, Healthy Reproductive Age Women, Healthy Perimenopausal Women
- What is being tested?
- C Type Natriüretic Peptide
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 71 participants
- Where
- 1 siteCyprus
- Study dates
- 24 Jul 2019to 20 Jan 2020
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy
- Regular cyclic menstruation for reproductive age group
Who cannot join
- No systemic disease(cardiac, renal...etc)
- Smoking
- Drug usage
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Serum Levels of C Type Natriuretic Peptide in Reproductive Age, Perimenopausal and Postmenopausal Women
Recent studies have shown that C natriuretic peptide (CNP) is produced from granulosa cells, increasing cumulative guanosine monophosphate (cGMP) production by affecting cumulus cells through natriuretic peptide receptors.It has been suggested that the transport of cGMP to oocyte via gap junctions causes a continuous increase in cyclic adenosine monophosphate (cAMP) levels within the oocyte. An important role of increased cAMP levels in oocyte is shown to suppress meiotic progression. Deoxyribonucleic acid (DNA) 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(LH) / human chorionic(hCG) stimulation. Human studies have shown that after ovulation induction, the CNP level in follicular fluid decreases following ovulatory dose of hCG (9).
Read the detailed description
In this prospective study, 60 patients are planned to recruite. Group 1 consists of 20 healthy reproductive aged women between 18-40 years old, with regular menstruation. Group 2 will include 20 patients in perimenopausal time period between 40-49 ages and in group 3 there will be20 postmenopausal women.
Age, gravida, parity and body mass index (BMI) data of all patients will be recorded. BMI is calculated by dividing the body weight in kilograms by the square of the height in meters. All patients will go under ultrasound examination by the same clinician (ACO). The number of antral follicles in group 1 and group 2 will be recorded. In addition, on the 2nd or 3rd day of menstruation, serum FSH, LH and E2 data of the patients in group 1 and 2 will be recorded.
For the last 6 months, patients with drug use that may affect menstruation like oral contraceptives, patients with cardiac or renal disease and therefore drug use, causes of infertility other than unexplained infertility, history of ovarian surgery, presence of polycystic ovary syndrome, and patients with irregular menstruation will be excluded for the study. In addition, patients with renal, cardiac, central nervous system and endocrine diseases will be excluded.
Morning fasting venous blood samples will be taken from the patients on the 2nd or 3rd day of the menstruation for group 1 and 2. All blood samples will be centrifuged on the day of collection and separated serum samples and will be kept at -80 degrees until the day of CNP test. Serum CNP levels of the patients will be analyzed by an enzyme-linked immunosorbent (ELISA) assay for human CNP in accordance with the manufacturer's instructions (SEA721Hu, ELISA Kit for Human CNP, Wuhan USCN Business Co., Ltd., Cloud-Clone Corp., CCC, USA).
Data will be analyzed using Statistical Package for Social Sciences software (SPSS v15, SPSS Inc, Chicago, IL, USA). The variables will be investigated using visual and analytical methods (histograms, homogeneity of variances test, Kolmogorov-Simirnov/Shapiro-Wilk's test) to determine whether or not they are normally distributed. Patient demographics and CNP values will be presented as median ± interquartile range. Gravida and parity will be demonstrated by frequency distribution. The correlation coefficients and their significance will be calculated using the Spearman test. P-values less than 0.05 will be regarded as statistically significant.
- Conditions
- Serum CNP Levels, Healthy Reproductive Age Women, Healthy Perimenopausal Women, Healthy Postmenopausal Women
- Being tested
- C Type Natriüretic Peptide
- Keywords
- c type natriuretic peptide, duration of menopause, menstrual cycle
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
C Type Natriüretic PeptideDiagnostic test
C Type Natriuretic Peptide will be measured with elisa method
| Study group | Role | What they receive |
|---|---|---|
| Reproductive age women | Active comparator | The healthy women between 18-40 years old. Receives: Diagnostic Test: C Type Natriüretic Peptide |
| Perimenopausal women | Active comparator | The healthy women between 40-49 years old. Receives: Diagnostic Test: C Type Natriüretic Peptide |
| Postmenopausal women | Active comparator | The healthy women that has been in to menopause more than a year Receives: Diagnostic Test: C Type Natriüretic Peptide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Serum C Type Natriuretic Peptide Levels
The comparison of serum levels of C type natriuretic peptide among different age groups
Measured: Second or Third Day of Menstruation
Secondary outcomes (3)
Correlation Between Serum CNP and Follicle Stimulating Hormone and Luteinizing Hormone Levels in Groups 1 and 2
Correlations between serum CNP vs Follicle Stimulating Hormone(FSH), CNP vs Luteinizing Hormone(LH) levels in groups 1 and 2
Measured: Second or Third Day of Menstruation
Correlation Between Serum CNP and Antral Follicle Count (AFC) in Groups 1 and 2
Correlation between serum CNP and antral follicle count (AFC) in groups 1 and 2 using Spearman test
Measured: Second or Third Day of Menstruation
Correlation Between Serum CNP and Estradiol Levels in Groups 1 and 2
Correlation of CNP vs. Estradiol levels in reproductive age and perimenopausal women
Measured: Second or Third Day of Menstruation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Jun 2019
- Study start24 Jul 2019
- Primary completion9 Jan 2020
- Study completion20 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (9)Papers the sponsor has linked to this study.
- Other trials for Serum CNP LevelsStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Model description
- In this study, there are three groups. Group 1:Women between 18-40 age, Group 2:Perimenopausal women (40-49 years), Group 3: Postmenopausal women.
- Masking
- Single blind
- Who is masked
- Investigator
- Enrolment
- 71 participants (actual)
Sponsor and investigators
- Lead sponsor
- Near East University, Turkey
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ali Cenk, Near East University, Turkey
- Investigators
- Özay, Principal investigator, Near East University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04000815
- Sponsor's protocol ID
- CenkOzay
- Acronym
- CO
- Status last verified
- Mar 2020
- First submitted
- 22 Jun 2019
- Last updated
- 11 Mar 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Only the name of study
Publications
Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010 Oct 15;330(6002):366-9. doi: 10.1126/science.1193573.
PubMed 20947764Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, Wang H, Ke H, Nikolaev VO, Jaffe LA. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development. 2009 Jun;136(11):1869-78. doi: 10.1242/dev.035238.
PubMed 19429786Vaccari S, Weeks JL 2nd, Hsieh M, Menniti FS, Conti M. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 2009 Sep;81(3):595-604. doi: 10.1095/biolreprod.109.077768. Epub 2009 May 27.
PubMed 19474061Tsafriri A, Chun SY, Zhang R, Hsueh AJ, Conti M. Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol. 1996 Sep 15;178(2):393-402. doi: 10.1006/dbio.1996.0226.
PubMed 8812137Thomas RE, Armstrong DT, Gilchrist RB. Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation. Dev Biol. 2002 Apr 15;244(2):215-25. doi: 10.1006/dbio.2002.0609.
PubMed 11944932Nogueira D, Albano C, Adriaenssens T, Cortvrindt R, Bourgain C, Devroey P, Smitz J. Human oocytes reversibly arrested in prophase I by phosphodiesterase type 3 inhibitor in vitro. Biol Reprod. 2003 Sep;69(3):1042-52. doi: 10.1095/biolreprod.103.015982. Epub 2003 May 28.
PubMed 12773402Lee KB, Zhang M, Sugiura K, Wigglesworth K, Uliasz T, Jaffe LA, Eppig JJ. Hormonal coordination of natriuretic peptide type C and natriuretic peptide receptor 3 expression in mouse granulosa cells. Biol Reprod. 2013 Feb 21;88(2):42. doi: 10.1095/biolreprod.112.104810. Print 2013 Feb.
PubMed 23255339Hiradate Y, Hoshino Y, Tanemura K, Sato E. C-type natriuretic peptide inhibits porcine oocyte meiotic resumption. Zygote. 2014 Aug;22(3):372-7. doi: 10.1017/S0967199412000615. Epub 2013 Jan 18.
PubMed 23331536Kawamura 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.
PubMed 21865234
Study at a glance
From the registry record, last updated by the sponsor on 11 Mar 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Serum Levels of C Type Natriuretic Peptide in Reproductive Age, Perimenopausal and Postmenopausal Women
- ClinicalTrials.gov ID
- NCT04000815
- Acronym / sponsor ID
- CO / CenkOzay
- Conditions
- Serum CNP Levels, Healthy Reproductive Age Women, Healthy Perimenopausal Women, Healthy Postmenopausal Women
- Keywords
- c type natriuretic peptide, duration of menopause, menstrual cycle
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 71 participants (actual)
- Lead sponsor
- Near East University, TurkeyUniversity, hospital or other
- Study start
- 24 Jul 2019 (actual)
- Primary completion
- 9 Jan 2020 (actual)
- Study completion
- 20 Jan 2020 (actual)
- First posted
- 27 Jun 2019 (actual)
- Results
- Posted 11 Mar 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent studies have shown that C natriuretic peptide (CNP) is produced from granulosa cells, increasing cumulative guanosine monophosphate (cGMP) production by affecting cumulus cells through natriuretic peptide receptors.It has been suggested that the transport of cGMP to oocyte via gap junctions causes a continuous increase in cyclic adenosine monophosphate (cAMP) levels within the oocyte. An important role of increased cAMP levels in oocyte is shown to suppress meiotic progression. Deoxyribonucleic acid (DNA) 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(LH) / human chorionic(hCG) stimulation. Human studies have shown that after ovulation induction, the CNP level in follicular fluid decreases following ovulatory dose of hCG (9).
Detailed description
In this prospective study, 60 patients are planned to recruite. Group 1 consists of 20 healthy reproductive aged women between 18-40 years old, with regular menstruation. Group 2 will include 20 patients in perimenopausal time period between 40-49 ages and in group 3 there will be20 postmenopausal women.
Age, gravida, parity and body mass index (BMI) data of all patients will be recorded. BMI is calculated by dividing the body weight in kilograms by the square of the height in meters. All patients will go under ultrasound examination by the same clinician (ACO). The number of antral follicles in group 1 and group 2 will be recorded. In addition, on the 2nd or 3rd day of menstruation, serum FSH, LH and E2 data of the patients in group 1 and 2 will be recorded.
For the last 6 months, patients with drug use that may affect menstruation like oral contraceptives, patients with cardiac or renal disease and therefore drug use, causes of infertility other than unexplained infertility, history of ovarian surgery, presence of polycystic ovary syndrome, and patients with irregular menstruation will be excluded for the study. In addition, patients with renal, cardiac, central nervous system and endocrine diseases will be excluded.
Morning fasting venous blood samples will be taken from the patients on the 2nd or 3rd day of the menstruation for group 1 and 2. All blood samples will be centrifuged on the day of collection and separated serum samples and will be kept at -80 degrees until the day of CNP test. Serum CNP levels of the patients will be analyzed by an enzyme-linked immunosorbent (ELISA) assay for human CNP in accordance with the manufacturer's instructions (SEA721Hu, ELISA Kit for Human CNP, Wuhan USCN Business Co., Ltd., Cloud-Clone Corp., CCC, USA).
Data will be analyzed using Statistical Package for Social Sciences software (SPSS v15, SPSS Inc, Chicago, IL, USA). The variables will be investigated using visual and analytical methods (histograms, homogeneity of variances test, Kolmogorov-Simirnov/Shapiro-Wilk's test) to determine whether or not they are normally distributed. Patient demographics and CNP values will be presented as median ± interquartile range. Gravida and parity will be demonstrated by frequency distribution. The correlation coefficients and their significance will be calculated using the Spearman test. P-values less than 0.05 will be regarded as statistically significant.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (investigator)
- Number of arms
- 3
- Model description
- In this study, there are three groups. Group 1:Women between 18-40 age, Group 2:Perimenopausal women (40-49 years), Group 3: Postmenopausal women.
| Arm | Type | Receives |
|---|---|---|
| Reproductive age women | Active comparator | Diagnostic Test: C Type Natriüretic PeptideThe healthy women between 18-40 years old. |
| Perimenopausal women | Active comparator | Diagnostic Test: C Type Natriüretic PeptideThe healthy women between 40-49 years old. |
| Postmenopausal women | Active comparator | Diagnostic Test: C Type Natriüretic PeptideThe healthy women that has been in to menopause more than a year |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Healthy
- Regular cyclic menstruation for reproductive age group
Key exclusion criteria (4 listed)
- No systemic disease(cardiac, renal...etc)
- Smoking
- Drug usage
- Pregnancy
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| C Type Natriüretic PeptideC Type Natriuretic Peptide will be measured with elisa method | Diagnostic test | Perimenopausal women, Postmenopausal women, Reproductive age women |
Primary outcome
Serum C Type Natriuretic Peptide Levels
Time frame: Second or Third Day of Menstruation
The comparison of serum levels of C type natriuretic peptide among different age groups
3 secondary outcomes
Correlation Between Serum CNP and Follicle Stimulating Hormone and Luteinizing Hormone Levels in Groups 1 and 2
Time frame: Second or Third Day of Menstruation
Correlation Between Serum CNP and Antral Follicle Count (AFC) in Groups 1 and 2
Time frame: Second or Third Day of Menstruation
Correlation Between Serum CNP and Estradiol Levels in Groups 1 and 2
Time frame: Second or Third Day of Menstruation
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Mar 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 20947764Zhang M, Su YQ, Sugiura K, Xia G, Eppig JJ. Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science. 2010 Oct 15;330(6002):366-9. doi: 10.1126/science.1193573.
- Background: PubMed 19429786Norris RP, Ratzan WJ, Freudzon M, Mehlmann LM, Krall J, Movsesian MA, Wang H, Ke H, Nikolaev VO, Jaffe LA. Cyclic GMP from the surrounding somatic cells regulates cyclic AMP and meiosis in the mouse oocyte. Development. 2009 Jun;136(11):1869-78. doi: 10.1242/dev.035238.
- Background: PubMed 19474061Vaccari S, Weeks JL 2nd, Hsieh M, Menniti FS, Conti M. Cyclic GMP signaling is involved in the luteinizing hormone-dependent meiotic maturation of mouse oocytes. Biol Reprod. 2009 Sep;81(3):595-604. doi: 10.1095/biolreprod.109.077768. Epub 2009 May 27.
- Background: PubMed 8812137Tsafriri A, Chun SY, Zhang R, Hsueh AJ, Conti M. Oocyte maturation involves compartmentalization and opposing changes of cAMP levels in follicular somatic and germ cells: studies using selective phosphodiesterase inhibitors. Dev Biol. 1996 Sep 15;178(2):393-402. doi: 10.1006/dbio.1996.0226.
- Background: PubMed 11944932Thomas RE, Armstrong DT, Gilchrist RB. Differential effects of specific phosphodiesterase isoenzyme inhibitors on bovine oocyte meiotic maturation. Dev Biol. 2002 Apr 15;244(2):215-25. doi: 10.1006/dbio.2002.0609.
- Background: PubMed 12773402Nogueira D, Albano C, Adriaenssens T, Cortvrindt R, Bourgain C, Devroey P, Smitz J. Human oocytes reversibly arrested in prophase I by phosphodiesterase type 3 inhibitor in vitro. Biol Reprod. 2003 Sep;69(3):1042-52. doi: 10.1095/biolreprod.103.015982. Epub 2003 May 28.
- Background: PubMed 23255339Lee KB, Zhang M, Sugiura K, Wigglesworth K, Uliasz T, Jaffe LA, Eppig JJ. Hormonal coordination of natriuretic peptide type C and natriuretic peptide receptor 3 expression in mouse granulosa cells. Biol Reprod. 2013 Feb 21;88(2):42. doi: 10.1095/biolreprod.112.104810. Print 2013 Feb.
- Background: PubMed 23331536Hiradate Y, Hoshino Y, Tanemura K, Sato E. C-type natriuretic peptide inhibits porcine oocyte meiotic resumption. Zygote. 2014 Aug;22(3):372-7. doi: 10.1017/S0967199412000615. Epub 2013 Jan 18.
- Background: PubMed 21865234Kawamura 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.
- Individual participant dataSharing planned: No. Only the name of study
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Özay principal investigator
Near East University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing C Type Natriüretic Peptide in people with Serum CNP Levels and Healthy Reproductive Age Women, run by Near East University, Turkey at 1 site in Cyprus.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 11 Mar 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Cyprus. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 11 Mar 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Serum C Type Natriuretic Peptide Levels (time frame: Second or Third Day of Menstruation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04000815, which also lists 9 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Mar 2020.