Development of A Novel Anti-Hyperglycemic Agent

新型抗高血糖药的研制

基本信息

批准号：
8196299
负责人：
Zhaoping Li
金额：
--
依托单位：
VA GREATER LOS ANGELES HEALTHCARE SYSTEM
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-04-01 至 2012-09-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8196299
关键词：
Adverse effects Adverse event Agreement Alzheimer&apos s Disease Amino Acids Animal Model Animals Asians Blood Blood Glucose Bone Density Brain Cardiovascular system Cause of Death Cell membrane Cells Centers for Disease Control and Prevention (U.S.)Chemistry Chronic Disease Clinical Clinical Trials Complex Copper Country Cytosol Defect Development Diabetes Mellitus Diabetes prevention Dipeptides Disease Dose Double-Blind Method Drops Environmental Risk Factor Enzyme Gene Enzymes European Event Expenditure FDA approved Fasting Future Gel Genes Genetic Genetic Polymorphism Glucagon Glucose Glucose Intolerance Glucose Transporter Glucose tolerance test Glycosylated hemoglobin A Health Healthcare Hematology Hepatic High Prevalence Hour Human Hyperglycemia Hypoglycemia Hypoglycemic Agents Impairment Injection of therapeutic agent Inpatients Insulin Insulin Receptor Insulin Resistance Insulinase Intake Intestines Kidney Lead Legal patent Leptin Literature Liver Liver Failure Marketing Mediating Medical Medical center Metformin Molecular Muscle Mutation National Health and Nutrition Examination Survey Nausea Non-Insulin-Dependent Diabetes Mellitus Obesity Oral Oral Administration Outcome Outcome Study Outpatients Patients Peptide Hydrolases Peptides Peripheral Pharmaceutical Preparations Pharmacy facility Phase Phase I Clinical Trials Pioglitazone Placebo Control Placebos Plasma Play Population Prevention Process Proteins Randomized Rattus Receptor Signaling Recruitment Activity Regimen Reporting Research Research Design Risk Role SLC2A1 gene Safety Services Severe Adverse Event Signal Transduction Stomach Sulfonylurea Compounds Symptoms Therapeutic Agents Thyroid Function Tests Tissues United States Urine Veterans Visit Vomiting Zinc Zinc deficiency absorption adiponectin analog base brain tissue capsule commercialization cost diabetic diabetic patient diet and exercise effective therapy experience fasting plasma glucose four-arm study functional disability glucogenesis glucose metabolism glucose output glucose uptake glycemic control histidylproline improved inhibitor/antagonist insulin sensitivity insulin signaling novel oral glucose tolerance primary outcome public health relevance receptor recycling rosiglitazone secondary outcome volunteer week trial

项目摘要

DESCRIPTION (provided by applicant): We have demonstrated that a cyclic dipeptide Cyclo (his-pro) plus zinc (Cyclo-Z) treatment improved clinical conditions of diabetes in various animal models and a phase 1 clinical trial. The main objective of this study is to demonstrate that this product is safe and effective for the treatment of human diabetes. Research Plan This is a randomized, double blinded, placebo-controlled, and parallel study. In this study, we will recruit 120 hypoglycemic drug naove type 2 diabetic patients and randomize them into 4 groups of 30 subjects each to compare the effects of a Cyclo-Z capsule containing CHP 0 (placebo), 3 mg (minimally effective), 9 mg (optimally effective), or 15 mg (no-additional effect) plus 20 mg zinc on diabetic symptoms in a 12-week trial period. The primary outcome of this study is improvement of hemoglubin A1c; secondary outcomes are fasting blood glucose, 2 hours postprandial glucose and glucose tolerance test. Safety will be assessed by the presence of severe adverse events (SAEs), adverse events (AEs), any changes of vital signs, physical exams, blood hematology, chemistry, liver, renal, thyroid function tests, urine analysis and zinc, copper levels. PUBLIC HEALTH RELEVANCE: Relevance to the Veterans Health Diabetes is a difficult and challenging chronic disease, and the seventh leading cause of death in the US (61). The DVA provides healthcare service to about 5.0 million patients throughout the country in 163 medical centers, and diabetes has high prevalence in VA patients. In the year 2000, 19.6% of VA patients had diabetes and this percentage increases annually by 2 % (61). Hence, the diabetic population among VA patients may approach 30% in the year 2008. About 30 % of pharmacy prescriptions of the VA Medical Centers are received by diabetic patients (62) and overall 23 % of pharmacy expenditures were related to patients' glycemic control in the year 2000. The expenditure for the outpatient visits was $214.8 million and inpatient expenditure was $1.45 billion in 1998 (63). Cyclo-Z may pose a benefit to more than 30% of veteran population. This new drug may ameliorate diabetes and reduce insulin-resistance which would greatly reduce the cost of inpatient and outpatient medical service as well as pharmacy expenditure. Three different patents with Cyclo-Z for the treatment of diabetes, obesity and Alzheimer's disease are now owned by the DVA and the phase 1 clinical trial has been completeds with favorable result. The outcome of the proposed phase 2a clinical trial will lead to an agreement with a major drug company by the DVA for Cyclo-Z marketing. We believe that Cyclo-Z will be effective and safe in the prevention and treatment of diabetes and that this novel drug will be beneficial to the health of many diabetic veteran patients.

描述（由申请人提供）：我们已经证明了环状二肽环（His-Pro）加锌（Cyclo-Z）治疗改善了各种动物模型中糖尿病的临床状况和1期临床试验。这项研究的主要目的是证明该产品对于治疗人类糖尿病是安全有效的。研究计划这是一项随机，双盲，安慰剂对照和并行研究。在这项研究中，我们将招募120名低血糖药物NAOVE 2型糖尿病患者，并将其随机分为40个受试者，以比较含有CHP 0（安慰剂），3 mg（最小值），9 mg（最佳）（最佳有效）或15 mg（无效效果）的含有CHP 0（安慰剂）的环形胶囊的效果，或者对20 mg ZINC症状。这项研究的主要结果是改善了血液卢比素A1c。次要结果是空腹血糖，餐后葡萄糖和葡萄糖耐受性测试2小时。安全将通过存在严重不良事件（SAE），不良事件（AES），生命体征，身体检查，血液血液学，化学，肝脏，肾脏，甲状腺功能测试，尿液分析和锌，铜水平的任何变化来评估安全性。公共卫生相关性：与退伍军人卫生糖尿病有关，是一种困难且具有挑战性的慢性疾病，也是美国第七主要死亡原因（61）。 DVA在163个医疗中心为全国约500万名患者提供医疗服务，糖尿病患者的患病率很高。在2000年，19.6％的VA患者患有糖尿病，这一百分比每年增加2％（61）。因此，在2008年，VA患者中的糖尿病人口可能接近30％。糖尿病患者（62例）收到了VA医疗中心的药房处方约30％，总计23％的药房支出与2000年患者的血糖控制有关。2000年，这笔票房的支出为214.8百万美元，$ 214.8.8（$ 214.8百万美元）。 Cyclo-Z可能对30％以上的资深人口造成好处。这种新药可以改善糖尿病并减少胰岛素抵抗，这将大大降低住院和门诊医疗服务以及药房支出的成本。 DVA现在拥有三种用于治疗糖尿病，肥胖和阿尔茨海默氏病治疗糖尿病，肥胖和阿尔茨海默氏病的专利，并且已经完成了1期临床试验，结果有利。拟议的2A期临床试验的结果将导致DVA与一家大型药品公司达成协议，以便Cyclo-Z营销。我们认为，Cyclo-Z对预防和治疗糖尿病将是有效且安全的，并且这种新型药物将对许多糖尿病退伍军人患者的健康有益。