Clinical trial NCT02302326: Involvement of Reticulum Endoplasmic Stress in the Physiopathology of Polycystic Ovary Syndrome
Official title: Involvement of Reticulum Endoplasmic Stress in the Physiopathology of Polycystic Ovary Syndrome: Possible Therapeutic Implications of Insulin Sensitizers.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Polycystic Ovary Syndrome
Keywords: reticulum endoplasmic stress
Polycystic Ovary Syndrome
mitochondrial function
insulin resistance
inflammation
myoinositol
metformin
oxidative stress
Lead sponsor: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
Sponsor class: OTHER
First posted: 2014-11-27
Enrollment: 50
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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. Furthermore, the investigators will assess the potential of insulin sensitizers as a treatment to control endoplasmic reticulum stress markers in PCOS patients.

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).

Eligibility criteria: 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

Primary outcomes:
measure: Changes in markers of endoplasmic reticulum stress in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
measure: Changes in markers of the insulin pathway in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
measure: Changes in inflammatory parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
measure: Changes in apoptotic parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
Secondary outcomes:
measure: Changes in anthropometric parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
measure: Changes in biochemical parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
measure: Changes in mitochondrial function parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
measure: Changes in endothelial function parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
timeFrame: 3 months
Other outcomes:
Locations:
city: Valencia
country: Spain
facility: Antonio Hernández
Study officials:
affiliation: FISABIO - University Hospital Dr Peset
name: Antonio Hernández, Phd, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.