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NCT Number: NCT02302326

Involvement of Reticulum Endoplasmic Stress in the Physiopathology of Polycystic Ovary Syndrome

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.

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Key information

Conditions

Polycystic Ovary Syndrome Adnexal Diseases Cysts Endocrine System Diseases Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Glucose Metabolism Disorders Gonadal Disorders Hyperinsulinism Inflammation Insulin Resistance Metabolic Diseases Neoplasms Nutritional and Metabolic Diseases Ovarian Cysts Ovarian Diseases Pathologic Processes Pathological Conditions, Signs and Symptoms Urogenital Diseases

Age range

18 year–45 year

Sex eligibility

Female

Study type

Interventional

Phase

Not applicable

Primary location

Antonio Hernández

Valencia, 46017, Spain

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

metformin

Drug

Dose: metformin (1700 mg / day) for 12 weeks

Myo-inositol + Folic acid

Dietary Supplement

Dose: Ovusitol® (4 g myo-inositol plus 400 micrograms of folic acid/day) for 12 weeks

Primary outcomes

  1. 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

  2. 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. 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

  4. 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

Secondary outcomes

  1. 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

  2. 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. 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

  4. 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

Sponsors and collaborators

Lead sponsor

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

Other

Registry information

Official study title

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

Acronym: PI12/1984

Important dates

Study start
2013
Primary completion
2019
Study completion
2019
First posted
Nov 27, 2014
Registry last updated
Feb 26, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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