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.

订正项目摘要/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，伴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、糖耐量异常和代谢综合征。一种可能改善多囊卵巢综合征两方面的药物是肌醇，它作为一种膳食补充剂在世界各地都可以买到。更具体地说，我们将研究d-chiro和myo-inositol的异构体组合。这种组合被认为通过恢复肌醇聚糖的失衡来改善胰岛素(和促性腺激素)信号传递，肌醇聚糖是细胞表面信号传递的第二信使。在这里，我们建议根据COSORT指南进行第一个动力充足且设计合理的临床试验，在剂量范围内的双盲随机对照试验(INSUPP-PCOS研究)中前瞻性地测试肌醇补充剂的效果。这将是一项为期三个月、三剂肌醇与安慰剂对照的四管齐下研究，减少高雄激素血症(基于血清睾酮水平)是性激素结合球蛋白(SHBG)和相关的游离雄激素指数、空腹胰岛素水平和口服葡萄糖挑战试验(OGTT)曲线下血糖水平变化的主要结果和关键的次要结果。假说是，接受肌醇补充的多囊卵巢综合征女性在高雄激素血症方面将有与剂量相关的减少。此外，我们认为，与安慰剂相比，肌醇的主要机制将是显著改善高雄激素血症(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结合球蛋白(SHBG)增加]、较低的皮脂含量、卵巢的窦状卵泡数量和抗米勒激素，所有这些都将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和成熟的多学科研究团队，他们成功地进行了多项相关试验。我们的试验具有很高的创新性和重要意义，因为我们正在研究一种广泛使用的补充剂，该补充剂可能对患有多囊卵巢综合征的女性生殖寿命的所有阶段都有广泛的指征。此外，通过登记试验，准备书面协议和操作和程序手册，并遵循CONSORT指南，我们将建立一个严格的堡垒，允许复制我们的试验。