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: 9770795
• 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/9770795
• 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： 多囊卵巢综合症（PCOS）是女性中最常见的内分泌疾病。它是一种异质性综合征，伴有慢性无排卵和雄激素过多症的生殖功能障碍，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。肌醇是一种可以改善多囊卵巢综合症的药物，它可以作为膳食补充剂在世界各地使用。更具体地说，我们将研究异构体、d-手性和肌醇的组合。该组合被认为可以通过恢复肌醇聚糖的不平衡来改善胰岛素（和促性腺激素）信号传导，肌醇聚糖是细胞表面信号传导的第二信使。我们在这里提出第一个充分动力和设计的临床试验，根据 CONSORT 指南，在剂量范围双盲随机对照试验（INSUPP-PCOS 研究）中前瞻性地测试肌醇补充剂的效果。这将是一项四臂研究，在三个月内比较三种剂量的肌醇与安慰剂，以减少高雄激素血症（基于血清睾酮水平）为主要结果，并以性激素结合球蛋白（SHBG）变化为主要次要结果）以及相关的游离雄激素指数、空腹胰岛素水平和口服葡萄糖激发试验（OGTT）的葡萄糖水平曲线下面积。假设患有多囊卵巢综合症的女性接受肌醇补充剂后，雄激素过多症会出现与剂量相关的减少。此外，我们认为，与安慰剂相比，肌醇的主要机制将是显着改善雄激素过多症（卵巢和肾上腺），如较低的游离雄激素指数[总睾酮减少和性激素致盲球蛋白（SHBG）增加]所证明的那样，皮脂量减少、卵巢窦卵泡数量减少以及抗苗勒氏管激素减少，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支经过验证且成熟的多学科研究人员团队，他们已成功进行了多项相关试验。我们的试验非常创新且意义重大，因为我们正在研究一种广泛使用的补充剂，它可能对患有多囊卵巢综合症的女性生殖寿命的所有阶段都有广泛的适应症。此外，通过注册试验、准备书面方案以及操作和程序手册，并遵循 CONSORT 指南，我们将建立严格的堡垒，以允许复制我们的试验。