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Pilot Study of the Efficacy of Mifepristone in Males with Type 2 Diabetes Mellitu

米非司酮对男性 2 型糖尿病患者疗效的初步研究

基本信息

批准号：
9566210
负责人：
Stanley Hsia
金额：
$ 10.76万
依托单位：
CHARLES R. DREW UNIVERSITY OF MED & SCI
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-06-01 至 2020-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9566210
关键词：
Adrenal Gland Hyperfunction Adverse effects Affect Anti-Progestin Beta Cell Blood Pressure Body Composition Body Weight Caucasians Cell physiology Clinical Clinical Trials Closure by clamp Counseling Development Diabetes Mellitus Diet Dose Double-Blind Method Enrollment Epidemic Esterified Fatty Acids Fatty Acids Follow-Up Studies Functional disorder Funding Glucocorticoid Receptor Glucocorticoids Glucose Gynecology Hepatic Hydrocortisone Hyperglycemia Hypoglycemic Agents Indirect Calorimetry Individual Insulin Intravenous infusion procedures Investigation Lead Life Style Lipids Low income Measures Mediating Mifepristone Minority Groups Molecular Non-Insulin-Dependent Diabetes Mellitus OGTT Oral Outcome Measure Patients Pharmaceutical Preparations Pharmacologic Substance Physiological Pilot Projects Pituitary-dependent Cushing&apos s disease Placebos Play Population Prevalence Procedures Productivity Protocols documentation Public Health Randomized Research Role Safety Secondary to Standardization Steroids Tablets Termination of pregnancy Whole Organism Woman blood glucose regulation body system career common treatment diabetic patient dosage efficacy study glucose disposal glucose output glycemic control improved in vivo insulin secretion insulin sensitivity male men oxidation public health relevance racial minority response treatment choice

项目摘要

DESCRIPTION (provided by applicant): Type 2 diabetes mellitus affects a growing number of individuals worldwide, and U.S. racial minority groups in particular. States of excess cortisol secretion (Cushing's disease) are associated with hyperglycemia and diabetes mellitus. Mifepristone inhibits the action of glucocorticoids and is currently approved for the treatment of hyperglycemia in patients with Cushing's disease. We propose to study the efficacy of mifepristone in patients with "usual" type 2 diabetes mellitus not associated with Cushing's disease, wherein more subtle abnormalities of cortisol action may still play a role in adversely affecting glucose control. Because mifepristone may also have gynecological side effects due to anti-‐progesterone effects and is also used clinically by women for pregnancy termination, we will restrict this initial pilot study to men only; if this project determines that it has favorabl actions on glucose lowering in men, it would then justify replicating this study in women to assess its glycemic benefits against those potential gynecological side effects. This pilot project will enroll 60 predominantly racial minority male subjects with type 2 diabetes mellitus inadequately controlled on combination oral agents. They will be randomized to receive either mifepristone 600 mg daily or matching placebo tablets, in a double blind fashion, for 3 months. All concurrent medication dosages will be kept constant, and consistent dietary and lifestyle counseling will be provided. Changes in glucose control, body weight and body composition, measures of insulin sensitivity and beta cell function from oral glucose tolerance testing, lipids, blood pressure, and clinical safety will be compared between groups. At baseline and at 3 months, a subset of 10 subjects will also undergo a euglycemic hyperinsulinemic clamp procedure to determine physiological responses to a standardized intravenous infusion of high-‐dose insulin, measuring insulin-‐mediated glucose uptke, insulin mediated suppression of hepatic glucose output, and suppression of non-‐ esterified fatty acids. Indirect calorimetry will also be performed simultaneously to determine changes in rates of insulin-‐stimulated glucose oxidation, non-‐oxidative glucose disposal and suppression of lipid oxidation. If successful, our findings will 1) support further follow-�up studies to delineate a potential clinical role for mifepristone as a new pharmaceutical choice for the treatment of "common-‐variety" type 2 diabetes; 2) support further molecular, cellular and in vivo investigations into the mechanisms of how usual physiological levels of glucocorticoids contribute to the pathophysiology of type 2 diabetes, both at the intracellular and whole organism levels; and 3) stimulate greater research productivity for the PI towards achieving independent funding for additional studies aimed at better understanding all of the above research aims.