NCT02302326

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.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
50

participants targeted

Target at P25-P50 for not_applicable

Timeline
Completed

Started Jan 2013

Longer than P75 for not_applicable

Geographic Reach
1 country

1 active site

Status
completed

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

Study Start

First participant enrolled

January 1, 2013

Completed
1.8 years until next milestone

First Submitted

Initial submission to the registry

October 29, 2014

Completed
29 days until next milestone

First Posted

Study publicly available on registry

November 27, 2014

Completed
5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2019

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2019

Completed
Last Updated

February 26, 2020

Status Verified

February 1, 2020

Enrollment Period

6.9 years

First QC Date

October 29, 2014

Last Update Submit

February 25, 2020

Conditions

Polycystic Ovary Syndrome

Keywords

reticulum endoplasmic stressPolycystic Ovary Syndromemitochondrial functioninsulin resistanceinflammationmyoinositolmetforminoxidative stress

Outcome Measures

Primary Outcomes (4)

  • 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

    3 months

  • 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

    3 months

  • 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

    3 months

  • 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

    3 months

Secondary Outcomes (4)

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

    3 months

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

    3 months

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

    3 months

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

    3 months

Study Arms (3)

Metformin

EXPERIMENTAL

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

Myo-inositol + folic acid

EXPERIMENTAL

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

Healthy women

NO INTERVENTION

Healthy untreated women adjusted for age and body mass index

Interventions

MetforminDRUG

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

Metformin
Myo-inositol + folic acidDIETARY_SUPPLEMENT

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

Myo-inositol + folic acid

Eligibility Criteria

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

You may qualify if:

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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Antonio Hernández

Valencia, 46017, Spain

Location

Related Publications (3)

  • 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.

    PMID: 23528141BACKGROUND

  • 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.

    PMID: 21778215BACKGROUND

  • 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.

    PMID: 19567514BACKGROUND

MeSH Terms

Conditions

Polycystic Ovary SyndromeInsulin ResistanceInflammation

Interventions

MetforminInositolFolic Acid

Condition Hierarchy (Ancestors)

Ovarian CystsCystsNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesGonadal DisordersEndocrine System DiseasesHyperinsulinismGlucose Metabolism DisordersMetabolic DiseasesNutritional and Metabolic DiseasesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic ChemicalsSugar AlcoholsAlcoholsCarbohydratesPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Officials

  • Antonio Hernández, Phd, MD

    FISABIO - University Hospital Dr Peset

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
PhD, MD

Study Record Dates

First Submitted

October 29, 2014

First Posted

November 27, 2014

Study Start

January 1, 2013

Primary Completion

December 1, 2019

Study Completion

December 1, 2019

Last Updated

February 26, 2020

Record last verified: 2020-02

Locations

ES(1)