Involvement of Reticulum Endoplasmic Stress in the Physiopathology of Polycystic Ovary Syndrome (PI12/1984)

February 25, 2020 updated by: Antonio Hernandez Mijares, Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

Involvement of Reticulum Endoplasmic Stress in the Physiopathology of Polycystic Ovary Syndrome: Possible Therapeutic Implications of Insulin Sensitizers.

The main objective of the present project is to evaluate the relevance of reticulum stress in the pathogenesis of polycystic ovary syndrome (PCOS), focusing particularly on the underlying mechanisms of insulin resistance, which is the origin of metabolic comorbidities. Furthermore, the investigators will assess the potential of insulin sensitizers as a treatment to control endoplasmic reticulum stress markers in PCOS patients.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

To do this, the investigators will evaluate anthropometric, biochemical and hormone parameters, lipid profile and cardiovascular risk markers (using enzymatic and biochemical techniques, nephelometry, enzyme-linked immunosorbent assay, radioimmunoassay), and markers of endoplasmic reticulum stress and the insulin pathway and inflammatory and apoptotic parameters (by means of Western blot, Real Time- Polymerase Chain Reaction (RT-PCR), Luminex® xMAP® Technology ) in patients with and without PCOS. The investigators' second objective is to evaluate (using the abovementioned methodology) the efficacy of different insulin sensitizers (myoinositol and metformin) administered to PCOS patients during a 3-month period after which the investigators will analyze different parameters of oxidative stress and mitochondrial function (using Clark electrode and fluorometric techniques).

Study Type

Interventional

Enrollment (Anticipated)

50

Phase

  • Not Applicable

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

  • Spain
      • Valencia, Spain, 46017
        • Antonio Hernández

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

Ages Eligible for Study

18 years to 45 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

Inclusion Criteria:

  • Women diagnosed with PCOS using the Rotterdam criteria
  • Women of reproductive age

Exclusion Criteria:

  • Organic, malignant, haematological, infectious or inflammatory disease
  • History of ischaemic heart disease (stroke or thromboembolism)
  • Diabetes mellitus,
  • Secondary causes of obesity (hypothyroidism, Cushing's syndrome)
  • Severe hypertension.
  • Smoking or alcohol habit

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: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Metformin
PCOS women began treatment with ER 500 mg metformin per day, and the dose was increased to 1000 mg after 2 weeks, and to 1700 mg/d after a further 2 weeks, and was maintained at this dose for a total of 12 weeks.
Drug: Metformin
Dose: metformin (1700 mg / day) for 12 weeks
Experimental: Myo-inositol + folic acid
PCOS women received a dietary supplement (Ovusitol® : 4 g myo-inositol plus 400 micrograms of folic acid) for 12 weeks
Dietary supplement: Myo-inositol + folic acid
Dose: Ovusitol® (4 g myo-inositol plus 400 micrograms of folic acid/day) for 12 weeks
No Intervention: Healthy women
Healthy untreated women adjusted for age and body mass index

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in markers of endoplasmic reticulum stress in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Markers of endoplasmic reticulum stress (78-kDa glucose-regulated protein (GRP78), ubiquitous translation initiation factor 2α (eIF2α), double-stranded RNA-activated protein kinase (PERK), inositol requiring enzyme 1 (IRE1α), X-box binding protein 1 (XBP-1)) were assessed by Western Blot and Real Time- Polymerase Chain Reaction (RT-PCR) in polymorphonuclear cells
3 months
Changes in markers of the insulin pathway in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Markers of the insulin pathway (c-Jun N-terminal kinase (JNK), insulin receptor substrate (IRS)) were assessed by Western Blot and Real Time- Polymerase Chain Reaction (RT-PCR) in polymorphonuclear cells
3 months
Changes in inflammatory parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Inflammatory parameters (nuclear factor κB (NF-κB), interleukin-6 (IL6), tumor necrosis factor α (TNFα)) were assessed by Western Blot, Real Time- Polymerase Chain Reaction (RT-PCR), or Luminex® xMAP® Technology in polymorphonuclear cells and serum
3 months
Changes in apoptotic parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Apoptotic parameters (transcription factor C/EBP homologous protein (CHOP) and caspase 12) were assessed by Western Blot and Real Time- Polymerase Chain Reaction (RT-PCR) in polymorphonuclear cells
3 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes in anthropometric parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Anthropometric (weight, height, body mass index and waist) and blood pressure parameters were evaluated
3 months
Changes in biochemical parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Glucose levels were measured using enzymatic techniques. Insulin was measured by an enzymatic luminescence technique. IR was calculated by homeostasis model assessment (HOMA). Total cholesterol and triglycerides were measured by employing enzymatic assays, and high density lipoprotein cholesterol (HDLc) concentrations were recorded with an autoanalyser using a direct method. Low-density lipoprotein cholesterol (LDLc) concentration was calculated using the Friedewald method. Luteinizing hormone (LH), follicle stimulating hormone (FSH) and testosterone were measured by specific radioimmunoassays. Dehydroepiandrosterone-sulfate (DHEAS), sex hormone-binding globulin (SHBG), androstenedione and testosterone were measured by specific chemiluminescence techniques. High-sensitive C-reactive protein (hsCRP) was quantified by a latex-enhanced immunonephelometric assay
3 months
Changes in mitochondrial function parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Oxidative stress markers ( mitochondrial oxygen (O2) consumption, membrane potential, glutathione, reactive oxygen species (ROS) and hydrogen peroxide levels, mitochondrial mass) were assessed by Clark electrode and fluorometric techniques
3 months
Changes in endothelial function parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
Time Frame: 3 months
Interactions between leukocytes and human umbilical vein endothelial cells were evaluated by flow chamber microscopy (leukocyte rolling velocity, leukocyte rolling flux and leukocyte adhesion). The vascular cell adhesion molecule 1 (VCAM-1), Intercellular adhesion molecule 1 (ICAM-1) and E-selectin were evaluated in serum by Luminex® 200 flow analyzer system
3 months

Collaborators and Investigators

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

Sponsor

Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana

Investigators

  • Principal Investigator: Antonio Hernández, Phd, MD, FISABIO - University Hospital Dr Peset

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

January 1, 2013

Primary Completion (Actual)

December 1, 2019

Study Completion (Actual)

December 1, 2019

Study Registration Dates

First Submitted

October 29, 2014

First Submitted That Met QC Criteria

November 24, 2014

First Posted (Estimate)

November 27, 2014

Study Record Updates

Last Update Posted (Actual)

February 26, 2020

Last Update Submitted That Met QC Criteria

February 25, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AHM-MET-2013-01

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.

Clinical Trials on Polycystic Ovary Syndrome

Clinical Trials on Metformin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Cyprus

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe