Involvement of Reticulum Endoplasmic Stress in the Physiopathology of Polycystic Ovary Syndrome: Possible Therapeutic Implications of Insulin Sensitizers.
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 1
- 主要终点
- Changes in apoptotic parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •Women diagnosed with PCOS using the Rotterdam criteria
- •Women of reproductive age
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Metformin (Drug)
Myo-inositol + folic acid
PCOS women received a dietary supplement (Ovusitol® : 4 g myo-inositol plus 400 micrograms of folic acid) for 12 weeks
干预措施: Myo-inositol + folic acid (Dietary Supplement)
结局指标
主要结局
Changes in apoptotic parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
时间窗: 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
Changes in inflammatory parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
时间窗: 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
Changes in markers of endoplasmic reticulum stress in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
时间窗: 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
Changes in markers of the insulin pathway in controls and pcos women before and after metformin/Myo-inositol + folic acid administration
时间窗: 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
次要结局
- 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)
- Changes in anthropometric parameters in controls and pcos women before and after metformin/Myo-inositol + folic acid administration(3 months)
研究者
Antonio Hernandez Mijares
PhD, MD
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana