New Approaches to Evaluation and Treatment of Acromegaly

肢端肥大症评估和治疗的新方法

• 批准号: 7279930
• 负责人: PAMELA U FREDA
• 金额: $ 13.79万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7279930
• 关键词: Acromegaly; Age; Area; Award; Biochemical; Biochemical Markers; Biological Assay; Body Composition; Body fat; C-reactive protein; Cardiac; Cardiovascular system; Chronic; Clinical; Clinical Markers; Clinical Research; Cohort Studies; Commit; Cross-Over Studies; Desire for food; Development; Diabetes Mellitus; Disease; Disease remission; End Point; Endocrine; Ensure; Environment; Evaluation; Funding; Glucose; Goals; Homocysteine; Homocystine; Insulin; Insulin-Like Growth Factor I; Interleukin-6; Lead; Lipids; Lipoprotein (a); Lipoprotein (a-); Measurement; Mentors; Metabolic; Metabolic Marker; Mid-Career Clinical Scientist Award (K24); Morbidity - disease rate; N.I.H. Research Support; Normal Range; Obesity; Operative Surgical Procedures; Oral; Other Therapy; Outcome; Patients; Pituitary Gland; Postoperative Period; Randomized; Range; Recurrence; Research; Research Personnel; Risk Marker; Sandostatin Lar Depot; Series; Serum; Structure; Therapeutic; Time; United States National Institutes of Health; Universities; Weight Gain; base; cardiovascular risk factor; career; cohort; disorder control; experience; falls; ghrelin; human GHR protein; improved; indexing; insulin sensitivity; mortality; novel; novel strategies; novel therapeutics; patient oriented; patient oriented research; pegvisomant; programs; prospective; somatostatin analog; success

DESCRIPTION (provided by applicant): The overall goal of this project is to support my continued professional development as an independent patient-oriented investigator and successfull mentor. My recent research focus has been to establish and validate optimal biochemical endpoints for the therapy of acromegaly. In these efforts, I have established a uniquely large cohort of patients, re-defined its biochemical criteria based on highly sensitive GH and IGF-I measurements and investigated novel therapeutic approaches to this disease. From these studies, we recognized the need to validate the biochemical endpoints for treatment against clinical disease activity in order to ensure truly "normal" clinical GH/IGF-I status. The scientific aims of this application correlate modern biochemical markers with short and long-term clinical outcomes and with metabolic and clinical disease activity in our cohort. The first 4 aims, funded by R01 DK06420 for which I am the PI, investigate the use of body composition to gauge disease activity, therapy with the novel GH receptor antagonist, pegvisomant, and the effect of dysregulated ghrelin secretion on biochemical and clinical disease activity markers in acromegaly. Two new aims extend those of my R01, investigating, in Aim 5, IGF-I levels as a markers of insulin sensitivity and body composition in acromegaly and in Aim 6, IGF-I as a marker of cardiovascular structure and function during therapy with the GH receptor anagonist, pegvisomant. These studies aim to improve our understanding of the optimal therapeutic endpoints and, in particular, our serum IGF-I goals for the treatment of acromegaly. My productive, ongoing, NIH funded clinical research program and 12 years of experience in patient-oriented research make me well suited to receive the K24 award. The additional funds provided by the K24 would allow me to raise my effort of NIH research support commensurate with the amount of time I currently commit to patient-oriented research and mentoring and also allow me to continue to expand in both these areas. The institutional environment at Columbia University, with a strong and diverse Endocrine Division, GCRC, Diabetes and Obesity Research Centers, is ideal for attracting fellows and conducting our research. The Mid-career Investigator Award in Patient Oriented Research is an ideal mechanism to ensure the necessary support I need to reduce clinical and administrative responsibilities, and ensure my continued success as a mentor and clinical researcher.

描述（由申请人提供）： 该项目的总体目标是支持我作为独立的面向患者的研究者和成功导师的持续专业发展。我最近的研究重点是建立和验证用于治疗肢端肥大的最佳生化终点。在这些努力中，我建立了一个独特的大量患者，基于高度敏感的GH和IGF-I测量值重新定义了其生化标准，并研究了该疾病的新型治疗方法。从这些研究中，我们认识到有必要验证对临床疾​​病活性治疗的生化终点，以确保真正的“正常”临床GH/IGF-I状态。该应用的科学目的将现代生化标记与短期和长期的临床结局以及我们同类中的代谢和临床疾病活动相关联。我是PI的R01 DK06420资助的前4个目标，研究了身体成分来衡量疾病活性，与新型GH受体拮抗剂，PEGVISOMANT的治疗以及不良调节的Ghrelin分泌对生物学和临床疾病活性标志物在accromegaly中的作用。两个新的目标扩展了我的R01的目标，在AIM 5中，IGF-I水平作为巨肥大中的胰岛素敏感性和身体成分标记，在AIM 6中，IGF-I作为心血管结构和功能的标志，在使用GH受体Anagonist，Pegvisomant的治疗过程中。这些研究旨在提高我们对最佳治疗终点的理解，尤其是我们的血清IGF-I治疗肢端肥大的目标。我的生产力，正在进行的NIH资助的临床研究计划和12年以患者为导向的研究经验使我非常适合获得K24奖。 K24提供的额外资金将使我能够提高NIH研究支持的努力，这与我目前致力于患者的研究和指导的时间相称，并且还使我能够继续在这两个领域进行扩展。哥伦比亚大学的机构环境，具有强大而多样化的内分泌部门，GCRC，糖尿病和肥胖研究中心，非常适合吸引研究员并进行我们的研究。以患者为导向的研究中的职业中期研究者奖是确保我需要减少临床和行政责任所需的必要支持的理想机制，并确保我作为导师和临床研究人员的持续成功。