NCT05958914

Brief Summary

The goal of this clinical trial is to characterize PCOS in terms of neuropeptide expression and to make the comparison between women with and without PCOS by going to analyze venous blood samples taken during the three phases of the ovarian cycle and follicular fluid, taken during the ovulatory phase as part of the oocyte pick-up. Specifically, the expression of neuropeptides such as CGRP, SP, VIP and enkephalins in the three phases of the ovarian cycle (follicular phase, ovulatory phase and luteal phase) will be evluated in three groups of women afferent to the medically assisted reproduction centre. In particular, Group 1 (control) will include women with regular ovarian cycle; Group 2 will include non-PCOS women undergoing ovarian stimulation and ICSI treatment; finally Group 3 will include women with PCOS undergoing ovarian stimulation and ICSI treatment. The main question\[s\] it aims to answer are:

  • Is there a fluctuation in blood neuropeptides concentrations of women with normal ovarian cycles during the three phases of the ovarian cycle?
  • Do PCOS women has altered levels of blood and follicolar fluid concentration of neuropepides with respect to non-PCOS individuals?
  • Is blood and follicolar fluid concentration of neuropeptide modulated by protocols of ovarian stimulation? Participants of Group 1 will follow the ovarian monitoring protocol, during which blood samples will be taken at the three phases of the ovarian cycle. Participants of Group 2 and 3 will undergo ovarian stimulation and ICSI treatment, followed by blood and follicular fluid sampling at the specified cycle phases. Researchers will compare the control Group 1 with Group 2 and 3 to see if there is a significative difference in the concentration of blood neuropeptides between the three groups at the same phase of the ovarian cycle. Moreover, they will evaluate if there is there significant different concentration of neuropeptides in follicolar fluid between group 2 and 3 during the ovulatory phase.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
45

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jul 2023

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

June 12, 2023

Completed
19 days until next milestone

Study Start

First participant enrolled

July 1, 2023

Completed
24 days until next milestone

First Posted

Study publicly available on registry

July 25, 2023

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2025

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2025

Completed
Last Updated

July 25, 2023

Status Verified

July 1, 2023

Enrollment Period

2 years

First QC Date

June 12, 2023

Last Update Submit

July 20, 2023

Conditions

PCOS

Keywords

PCOSneuropeptidesenkephalinsSPCGRPVIP

Outcome Measures

Primary Outcomes (4)

  • Evaluation of the normal fluctuation of CGRP during the ovarian cycle in non-PCOS women

    To evaluate the absolute difference of blood concentration of CGRP and the relative difference of its concentration \[100 - (CFO\*100/CFF) and 100 - (CFL\*100/CFO)\] in the three phases of the ovarian cycle: follicular phase (FF) (day 5-10 postmenstrual), ovulatory phase (FO) (day 14) and luteal phase (FL) (day 18-23) in women of childbearing age with regular ovarian cycle afferent to the PMA Center (Group 1).

    5 days postmenstrual, 14 days postmenstrual, 18 days postmenstrual

  • Evaluation of the normal fluctuation of SP during the ovarian cycle in non-PCOS women

    To evaluate the absolute difference of blood concentration of SP and the relative difference of its concentration \[100 - (CFO\*100/CFF) and 100 - (CFL\*100/CFO)\] in the three phases of the ovarian cycle: follicular phase (FF) (day 5-10 postmenstrual), ovulatory phase (FO) (day 14) and luteal phase (FL) (day 18-23) in women of childbearing age with regular ovarian cycle afferent to the PMA Center (Group 1).

    5 days postmenstrual, 14 days postmenstrual, 18 days postmenstrual

  • Evaluation of the normal fluctuation of VIP during the ovarian cycle in non-PCOS women

    To evaluate the absolute difference of blood concentration of VIP and the relative difference of its concentration \[100 - (CFO\*100/CFF) and 100 - (CFL\*100/CFO)\] in the three phases of the ovarian cycle: follicular phase (FF) (day 5-10 postmenstrual), ovulatory phase (FO) (day 14) and luteal phase (FL) (day 18-23) in women of childbearing age with regular ovarian cycle afferent to the PMA Center (Group 1).

    5 days postmenstrual, 14 days postmenstrual, 18 days postmenstrual

  • Evaluation of the normal fluctuation of enkephalins during the ovarian cycle of non PCOS women

    To evaluate the absolute difference of blood concentration of enkephalins and the relative difference of its concentration \[100 - (CFO\*100/CFF) and 100 - (CFL\*100/CFO)\] in the three phases of the ovarian cycle: follicular phase (FF) (day 5-10 postmenstrual), ovulatory phase (FO) (day 14) and luteal phase (FL) (day 18-23) in women of childbearing age with regular ovarian cycle afferent to the PMA Center (Group 1).

    5 days postmenstrual, 14 days postmenstrual, 18 days postmenstrual

Secondary Outcomes (20)

  • Evaluation of the fluctuation of CGRP during the ovarian cycle in non-PCOS women undergoing ICSI treatment

    5 days before egg pick-up, day of egg pick up, 10 days after egg pick-up

  • Evaluation of the fluctuation of SP during the ovarian cycle in non-PCOS women undergoing ICSI treatment

    5 days before egg pick-up, day of egg pick up, 10 days after egg pick-up

  • Evaluation of the fluctuation of enkephalins during the ovarian cycle in non-PCOS women undergoing ICSI treatment

    5 days before egg pick-up, day of egg pick up, 10 days after egg pick-up

  • Evaluation of the fluctuation of VIP during the ovarian cycle in non-PCOS women undergoing ICSI treatment

    5 days before egg pick-up, day of egg pick up, 10 days after egg pick-up

  • Evaluation of the fluctuation of CGRP during the ovarian cycle in PCOS women undergoing ICSI treatment

    5 days before egg pick-up, day of egg pick up, 10 days after egg pick-up

  • +15 more secondary outcomes

Study Arms (3)

Arm 1

EXPERIMENTAL

women with regular ovarian cycle. Patients, as per normal clinical practice, will undergo three blood draws in the follicular, ovulatory and luteal phases. Biological samples will be analyzed for the concentration of neuropeptides (enkephalins, CGRP, SP and VIP)

Diagnostic Test: Dosage of ematic CGRPDiagnostic Test: Dosage of ematic SPDiagnostic Test: Dosage of ematic enkephalinsDiagnostic Test: Dosage of ematic VIP

Arm 2

EXPERIMENTAL

non-PCOS women undergoing ovarian stimulation and ICSI treatment. Patients will undergo ovarian stimulation treatment with gonadotropins and egg retrieval. As part of this process, as per clinical practice, blood and follicular fluid sampling will be performed. Biological samples will be analyzed for the concentration of neuropeptides (enkephalins, CGRP, SP and VIP)

Diagnostic Test: Dosage of ematic CGRPDiagnostic Test: Dosage of ematic SPDiagnostic Test: Dosage of ematic enkephalinsDiagnostic Test: Dosage of ematic VIPDiagnostic Test: Dosage of CGRP in follicolar fluidDiagnostic Test: Dosage of SP in follicolar fluidDiagnostic Test: Dosage of enkephalins in follicolar fluidDiagnostic Test: Dosage of VIP in follicolar fluid

Arm 3

EXPERIMENTAL

PCOS women undergoing ovarian stimulation and ICSI treatment. Patients will undergo ovarian stimulation treatment with gonadotropins and egg retrieval. As part of this process, as per clinical practice, blood and follicular fluid sampling will be performed. Biological samples will be analyzed for the concentration of neuropeptides (enkephalins, CGRP, SP and VIP)

Diagnostic Test: Dosage of ematic CGRPDiagnostic Test: Dosage of ematic SPDiagnostic Test: Dosage of ematic enkephalinsDiagnostic Test: Dosage of ematic VIPDiagnostic Test: Dosage of CGRP in follicolar fluidDiagnostic Test: Dosage of SP in follicolar fluidDiagnostic Test: Dosage of enkephalins in follicolar fluidDiagnostic Test: Dosage of VIP in follicolar fluid

Interventions

Dosage of ematic CGRPDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of CGRP in blood

Arm 1Arm 2Arm 3
Dosage of ematic SPDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of SP in blood

Arm 1Arm 2Arm 3
Dosage of ematic enkephalinsDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of enkephalins in blood

Arm 1Arm 2Arm 3
Dosage of ematic VIPDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of VIP in blood

Arm 1Arm 2Arm 3
Dosage of CGRP in follicolar fluidDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of CGRP in follicolar fluid

Arm 2Arm 3
Dosage of SP in follicolar fluidDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of SP in follicolar fluid

Arm 2Arm 3
Dosage of enkephalins in follicolar fluidDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of enkephalins in follicolar fluid

Arm 2Arm 3
Dosage of VIP in follicolar fluidDIAGNOSTIC_TEST

Immunoassay kit for the evaluation of VIP in follicolar fluid

Arm 2Arm 3

Eligibility Criteria

Age18 Years - 45 Years
Sexfemale
Healthy VolunteersYes
Age GroupsAdult (18-64)

You may qualify if:

  • infertile women
  • BMI between 18 and 30 kg/m2,
  • basal FSH \< 10 IU/L,
  • number of antral follicles (2-10 m) per ovary \> 10,
  • regular uterine cavity assessed by hysterosalpinography, sonohysterography or hysteroscopy, and hematologic and biochemical parameters within normal limits will be included in the study, euthyroid status (with or without treatment)
  • In case of women with PCOS, it should be diagnosed according to the Rotterdam criteria (The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group (2004) Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome (PCOS).
  • No restrictions regarding the indication of infertility.

You may not qualify if:

  • presence of ovaries inaccessible to oocyte pick-up,
  • presence of sactosalpinx, heterologous fertilization,
  • contraindication to pregnancy,
  • atypical genital discharge of unspecified cause,
  • uncontrolled dystothyroidism, presence of neoplasms,
  • severe alteration of liver or kidney function, taking medications that may interfere with the study.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Perugia, Piazza Menghini 1, S. Andrea delle Fratte.

Perugia, Umbria, 06156, Italy

RECRUITING

Related Publications (10)

  • International evidence-based guidelines for the assessment and management of polycystic ovary syndrome 2018. Melbourne, Monash University

    BACKGROUND

  • Slowey MJ. Polycystic ovary syndrome: new perspective on an old problem. South Med J. 2001 Feb;94(2):190-6.

    PMID: 11235033BACKGROUND

  • Pasquali R. Metabolic Syndrome in Polycystic Ovary Syndrome. Front Horm Res. 2018;49:114-130. doi: 10.1159/000485995. Epub 2018 Apr 5.

    PMID: 29894990BACKGROUND

  • Tekin G, Tekin A, Kilicarslan EB, Haydardedeoglu B, Katircibasi T, Kocum T, Erol T, Colkesen Y, Sezgin AT, Muderrisoglu H. Altered autonomic neural control of the cardiovascular system in patients with polycystic ovary syndrome. Int J Cardiol. 2008 Oct 30;130(1):49-55. doi: 10.1016/j.ijcard.2007.08.037. Epub 2007 Dec 4.

    PMID: 18055040BACKGROUND

  • Sverrisdottir YB, Mogren T, Kataoka J, Janson PO, Stener-Victorin E. Is polycystic ovary syndrome associated with high sympathetic nerve activity and size at birth? Am J Physiol Endocrinol Metab. 2008 Mar;294(3):E576-81. doi: 10.1152/ajpendo.00725.2007. Epub 2008 Jan 15.

    PMID: 18198350BACKGROUND

  • Morales-Ledesma L, Trujillo Hernandez A, Ramirez MI, Rosas G, Linares R. Administration of a VIP-antagonist in vivo modifies ovarian hormone secretion in a rat model with polycystic ovary syndrome. Life Sci. 2021 Jan 15;265:118792. doi: 10.1016/j.lfs.2020.118792. Epub 2020 Nov 18.

    PMID: 33220286BACKGROUND

  • Ilie IR. Neurotransmitter, neuropeptide and gut peptide profile in PCOS-pathways contributing to the pathophysiology, food intake and psychiatric manifestations of PCOS. Adv Clin Chem. 2020;96:85-135. doi: 10.1016/bs.acc.2019.11.004. Epub 2019 Dec 12.

    PMID: 32362321BACKGROUND

  • Moore AM, Campbell RE. Polycystic ovary syndrome: Understanding the role of the brain. Front Neuroendocrinol. 2017 Jul;46:1-14. doi: 10.1016/j.yfrne.2017.05.002. Epub 2017 May 25.

    PMID: 28551304BACKGROUND

  • Kozlowska A, Wojtkiewicz J, Majewski M, Jana B. Localization of substance P, calcitonin gene related peptide and galanin in the nerve fibers of porcine cystic ovaries. Folia Histochem Cytobiol. 2011;49(4):622-30. doi: 10.5603/fhc.2011.0085.

    PMID: 22252756BACKGROUND

  • Zhang Z, Gong F, Lu GX. Plasma level of calcitonin gene-related peptide in patients with polycystic ovary syndrome and its relationship to hormonal and metabolic parameters. Peptides. 2012 Apr;34(2):343-8. doi: 10.1016/j.peptides.2012.01.018. Epub 2012 Jan 31.

    PMID: 22314079BACKGROUND

Study Officials

  • Sandro Gerli, Professor

    University Of Perugia

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Sandro Gerli, Professor

CONTACT

368434624sandro.gerli@unipg.it

Alessandro Favilli, PhD

CONTACT

3292270705alessandro.favilli@unipg.it

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
BASIC SCIENCE
Intervention Model
PARALLEL
Model Details: The study involves an enrollment of 45 total patients, referred to the Medically assisted reproduction Center, divided into 3 groups, of 15 patients each: Group 1 (control) women with regular ovarian cycle; Group 2- non-PCOS women undergoing ovarian stimulation and ICSI treatment; Group 3- women with PCOS undergoing ovarian stimulation and ICSI treatment
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Associate Professor of Obstetrics and Gynecology

Study Record Dates

First Submitted

June 12, 2023

First Posted

July 25, 2023

Study Start

July 1, 2023

Primary Completion

July 1, 2025

Study Completion

October 1, 2025

Last Updated

July 25, 2023

Record last verified: 2023-07

Data Sharing

IPD Sharing
Will not share

Locations

IT(1)