Inositol Supplementation to Treat Reproductive and Metabolic Dysfunction in Polycystic Ovary Syndrome: A Double Blind RCT (INSUPP-PCOS)

补充肌醇治疗多囊卵巢综合征的生殖和代谢功能障碍：双盲随机对照试验 (INSUPP-PCOS)

• 批准号: 10005132
• 负责人: RICHARD S. LEGRO
• 金额: $ 52.7万
• 依托单位: PENNSYLVANIA STATE UNIV HERSHEY MED CTR
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10005132
• 关键词: Address; Adrenal Glands; Advocate; Affect; Age; Androgens; Anovulation; Antral; Area Under Curve; Body Weight decreased; Case Report Form; Cell surface; Chronic; Clinical Trials Design; Clomiphene; Consensus; Contraceptive Usage; Deterioration; Dose; Double-Blind Method; Endocrine; Fasting; Female; Free Will; Functional disorder; Globulins; Glucose; Glucose Intolerance; Glucose tolerance test; Gonadal Steroid Hormones; Gonadotropins; Guidelines; Health; Hyperandrogenism; Infertility; Inositol; Insulin; Insulin Resistance; Isomerism; Letrozole; Life Style Modification; Longevity; Manuals; Measures; Menopause; Metabolic; Metabolic dysfunction; Metabolic syndrome; Metformin; Obesity; Oral; Oral Contraceptives; Ovarian; Ovary; Overweight; Ovulation Induction; Patients; Pharmaceutical Preparations; Phase; Placebos; Polycystic Ovary Syndrome; Population; Probability; Procedures; Protocols documentation; Randomized Controlled Trials; Reproducibility; Research Personnel; Role; Sebum; Second Messenger Systems; Serum; Sex Hormone-Binding Globulin; Signal Transduction; Stereoisomer; Supplementation; Syndrome; Testing; Testosterone; Thiazolidinediones; Weight; Woman; base; clinically relevant; dietary supplements; effective therapy; efficacy study; experience; glucose metabolism; glucose tolerance; improved; indexing; infertility treatment; innovation; insulin sensitizing drugs; insulin signaling; mullerian-inhibiting hormone; multidisciplinary; operation; primary outcome; prospective test; reproductive; risk benefit ratio; secondary outcome; trial design; young woman

The revised project summary/abstract: Polycystic ovary syndrome (PCOS) is the most common endocrinopathy among women. It is a heterogeneous syndrome with reproductive dysfunction of chronic anovulation and hyperandrogenism, as well as metabolic dysfunction: insulin resistance, glucose intolerance and metabolic syndrome. One such medication that may improve both aspects of PCOS is inositol and it is available throughout the world as a dietary supplement. More specifically we will study a combination of isomers, d-chiro and myo-inositol. The combination is thought to improve insulin (and gonadotropin) signaling by restoring an imbalance in inositolglycans which are second messengers in cell surface signaling. We propose here the first adequately powered and designed clinical trial to test prospectively the effects of inositol supplementation in a dose ranging double blind randomized controlled trial, (the INSUPP- PCOS study) according to CONSORT guidelines. This will be a four armed study of three doses of inositol vs. placebo over a three month period with the reduction in hyperandrogenism (based on serum testosterone levels) as the primary outcome and key secondary outcomes of the change in sex hormone binding globulin(SHBG) and the related free androgen index, fasting insulin levels and area under the curve glucose levels from an oral glucose challenge test (OGTT). The hypothesis is that women with PCOS who receive inositol supplementation will have a dose related reduction in hyperandrogenism. Further, we propose that the primary mechanism of inositol will be a significant improvement in hyperandrogenism (both ovarian and adrenal) vs. placebo, as documented by a lower free androgen index [decreased total testosterone and increased sex hormone blinding globulin (SHBG)], lower sebum measures and lower antral follicle counts of the ovary and anti-Mullerian hormone, all of which will correlate with the decrease in hyperandrogenism. We bring to this study a proven and established team of multi-disciplinary researchers who have successfully conducted multiple related trials. Our trial is highly innovative and significant, as we are studying a widely used supplement that may have a broad indication across all phases of the reproductive lifespan of a woman with PCOS. Further by registering the trial, preparing a written protocol and manual of operations and procedures and by following CONSORT guidelines we will be establishing a rigorous bulwark to allow for replication of our trial.

修订后的项目摘要/摘要： 多囊卵巢综合征（PCOS）是女性最常见的内分泌疾病。它是一种异质性综合征，具有慢性无排卵和高雄激素血症的生殖功能障碍，以及代谢功能障碍：胰岛素抵抗，葡萄糖耐受不良和代谢综合征。一种可以改善PCOS两个方面的药物是肌醇，它在世界各地都可以作为膳食补充剂。更具体地说，我们将研究异构体的组合，d-手性和肌醇。该组合被认为通过恢复肌醇聚糖（细胞表面信号传导中的第二信使）的不平衡来改善胰岛素（和促性腺激素）信号传导。我们在这里提出了第一个充分的动力和设计的临床试验，以前瞻性地测试肌醇补充剂的影响，在剂量范围双盲随机对照试验，（INSUPP- PCOS研究）根据CONSORT指南。这将是一项为期三个月的四组研究，三种剂量的肌醇与安慰剂相比，高雄激素血症的减少（基于血清睾酮水平）作为主要结局，性激素结合球蛋白（SHBG）和相关游离雄激素指数变化的关键次要结局，空腹胰岛素水平和口服葡萄糖激发试验（OGTT）的葡萄糖曲线下面积水平。该假说认为，接受肌醇补充剂的PCOS妇女高雄激素血症将有剂量相关的减少。此外，我们提出肌醇的主要机制是与安慰剂相比，高雄激素血症（卵巢和肾上腺）的显著改善，如通过较低的游离雄激素指数[降低的总睾酮和增加的性激素致盲球蛋白（SHBG）]，较低的皮脂测量和较低的卵巢窦卵泡计数和抗苗勒管激素，所有这些都与高雄激素血症的减少相关。我们为这项研究带来了一个经过验证和建立的多学科研究人员团队，他们已经成功地进行了多项相关试验。我们的试验具有高度创新性和重要性，因为我们正在研究一种广泛使用的补充剂，该补充剂可能在多囊卵巢综合症女性生殖寿命的各个阶段具有广泛的适应症。此外，通过注册试验、准备书面方案和操作手册以及遵循CONSORT指南，我们将建立一个严格的堡垒，以允许复制我们的试验。