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Polycystic Ovary SyndromePI12/1984NCT02302326

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

A study testing Metformin and Myo-inositol + folic acid in people with Polycystic Ovary Syndrome, run by Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana at 1 site in Spain.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 45 years, women onlyHealthy volunteers can take part
Conditions the study is for
Polycystic Ovary Syndrome
What is being tested?
Metformin and Myo-inositol + folic acid
Could I receive a placebo?
No, everyone receives an active treatment
How many people
50 participants
Where
1 siteSpain
Study dates
Jan 2013to Dec 2019
Phase
Interventional
Are there results?
None posted in the registry

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 45 years
  • Women only
  • Healthy volunteers accepted
  • Adult

Who may be able to join

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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

Spain1 site

  • Antonio Hernández

    Valencia, 46017

Other trials in Spain

About this study

Official title: 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.

Read the 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).

Being tested
Metformin, Myo-inositol + folic acid
Keywords
reticulum endoplasmic stress, Polycystic Ovary Syndrome, mitochondrial function, insulin resistance, inflammation, myoinositol, metformin, oxidative stress
Medical subject headings
Polycystic Ovary Syndrome, Insulin Resistance, Inflammation

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • MetforminDrug

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

  • Myo-inositol + folic acidDietary supplement

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

Study groups in NCT02302326
Study groupRoleWhat they receive
MetforminExperimentalPCOS 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.
Receives: Drug: Metformin
Myo-inositol + folic acidExperimentalPCOS women received a dietary supplement (Ovusitol® : 4 g myo-inositol plus 400 micrograms of folic acid) for 12 weeks
Receives: Dietary Supplement: Myo-inositol + folic acid
Healthy womenNo interventionHealthy untreated women adjusted for age and body mass index

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Changes in markers of endoplasmic reticulum stress in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    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

    Measured: 3 months

  2. Changes in markers of the insulin pathway in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    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

    Measured: 3 months

  3. Changes in inflammatory parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    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

    Measured: 3 months

  4. Changes in apoptotic parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    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

    Measured: 3 months

Secondary outcomes (4)

  1. Changes in anthropometric parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    Anthropometric (weight, height, body mass index and waist) and blood pressure parameters were evaluated

    Measured: 3 months

  2. Changes in biochemical parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    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

    Measured: 3 months

  3. Changes in mitochondrial function parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    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

    Measured: 3 months

  4. Changes in endothelial function parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration

    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

    Measured: 3 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted27 Nov 2014 (estimated)
  2. Study startJan 2013
  3. Primary completionDec 2019
  4. Study completionDec 2019

Resources

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
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
50 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02302326
Sponsor's protocol ID
AHM-MET-2013-01
Acronym
PI12/1984
Status last verified
Feb 2020
First submitted
29 Oct 2014
Last updated
26 Feb 2020
Results posted
No
Data monitoring committee
No

Publications

  • Hernandez-Mijares A, Banuls C, Gomez-Balaguer M, Bergoglio M, Victor VM, Rocha M. Influence of obesity on atherogenic dyslipidemia in women with polycystic ovary syndrome. Eur J Clin Invest. 2013 Jun;43(6):549-56. doi: 10.1111/eci.12080. Epub 2013 Mar 26.

    PubMed 23528141

  • Victor VM, Rocha M, Banuls C, Alvarez A, de Pablo C, Sanchez-Serrano M, Gomez M, Hernandez-Mijares A. Induction of oxidative stress and human leukocyte/endothelial cell interactions in polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab. 2011 Oct;96(10):3115-22. doi: 10.1210/jc.2011-0651. Epub 2011 Jul 21.

    PubMed 21778215

  • Victor VM, Rocha M, Banuls C, Sanchez-Serrano M, Sola E, Gomez M, Hernandez-Mijares A. Mitochondrial complex I impairment in leukocytes from polycystic ovary syndrome patients with insulin resistance. J Clin Endocrinol Metab. 2009 Sep;94(9):3505-12. doi: 10.1210/jc.2009-0466. Epub 2009 Jun 30.

    PubMed 19567514

Questions about this trial

What is this clinical trial studying?

A study testing Metformin and Myo-inositol + folic acid in people with Polycystic Ovary Syndrome, run by Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana at 1 site in Spain.

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 6 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 26 Feb 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 Spain. 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?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

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). The study lists 4 primary outcomes in all. 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 NCT02302326, which also lists 3 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 26 Feb 2020.

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