Management of Cancer-Treatment-Induced Bone Loss

癌症治疗引起的骨质流失的管理

• 批准号: 9123535
• 负责人: Luke Joseph Peppone
• 金额: $ 14.49万
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9123535
• 关键词: Academic Training; Adjuvant; Adverse effects; Aerobic; Age; Applications Grants; Area; Aromatase Inhibitors; Arthralgia; Assisted Living Facilities; Award; Behavior Therapy; Binding; Biological; Biology; Bone Density; Breast; Breast Cancer Patient; Cancer Control; Cholecalciferol; Clinical; Clinical Investigator; Clinical Trials; Clinical Trials Design; Conduct Clinical Trials; Controlled Clinical Trials; Data; Development; Development Plans; Diagnosis; Doctor of Philosophy; Dose; Epidemiologist; Evidence Based Medicine; Exercise; Female; Foundations; Fracture; Genes; Genetic; Genetic Polymorphism; Goals; Grant; Health; Home environment; Incidence; Intervention; K-Series Research Career Programs; Knowledge; Malignant Neoplasms; Master of Public Health; Measurement; Mentors; Methods; Morbidity - disease rate; Pathogenesis; Pathway interactions; Pharmacology; Phase; Phase III Clinical Trials; Physiology; Population; Postmenopause; Prevention; Preventive; Preventive Intervention; Preventive measure; Quality of life; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Research; Research Personnel; Research Project Grants; Risk; Severities; Side; Single Nucleotide Polymorphism; Study Section; Techniques; Testing; Tetanus Helper Peptide; Time; Training; Training Activity; Treatment Efficacy; Vitamin D; Vitamin D supplementation; Vitamin D3 Receptor; Walking; Weight-Bearing state; Woman; aged; arm; base; bisphosphonate; bone; bone health; bone loss; bone metabolism; cancer therapy; career development; design; dietary supplements; efficacy testing; evidence base; exercise intervention; exercise program; experience; genetic analysis; improved; innovation; malignant breast neoplasm; mortality; multidisciplinary; phase III trial; prevent; resistance exercise; skills; three-arm study; treatment planning

DESCRIPTION (provided by applicant): Luke Peppone, Ph.D., M.P.H., a cancer epidemiologist, is applying for a mentored career development award to expand his research skills and become an independent clinical investigator in cancer control with a focus on developing and testing interventions to treat cancer-treatment-induced bone loss (CTIBL). This proposal will assess interventions aimed at preventing CTIBL in postmenopausal breast cancer patients caused by aromatase inhibitor (AI) therapy, which results in a 2- to 4-fold increase in bone loss and significantly increase fracture risk in this population. The research project will tet the efficacy of high-dose vitamin D supplementation plus a personalized weight-bearing exercise program to prevent CTIBL. Career Development Plan: Dr. Peppone's previous experience as an epidemiologist specializing in cancer, combined with his ongoing training as a clinical cancer control researcher, makes him well-suited to become a independent researcher with a focus on the pathogenesis and treatment of CTIBL. His training goals will expand upon his knowledge and are divided into three training aims: 1) to develop expertise in the biology, physiology, genetics, and measurement of CTIBL, 2) to gain experience as a PI in the design, conduct, and analysis of Phase II/III randomized controlled clinical trials, and 3) to gain experience in the testing and implementation of a nutritional supplement intervention (vitamin D) and behavioral interventions (exercise) for CTIBL. Dr. Gary Morrow, a leading cancer control researcher for the past thirty years, will serve as Dr. Peppone's principal senior mentor and offer guidance in the area of clinical trial conduct. Co-mentor Dr. Randy Rosier and Advisor Dr. Alissa Huston will provide expertise in the biology, physiology, and contributing factors of CTIBL. Co-mentor Dr. Mary Reid and Advisor Donald Trump offer experience in the efficacy and pharmacology of vitamin D for the management of CTIBL, while co-mentor Dr. Karen Mustian will train Dr. Peppone in the development and implementation of exercise interventions for CTIBL. Advisor Dr. Godfrey will provide training in genetic analysis and Advisor Dr. Heckler will offer statistical training. Research Plan: The proposed pilot RCT, based upon both biological plausibility and feasibility data, is a three-arm study that tests two interventions for the prevention of cancer-treatment-induced bone loss in 105 moderately vitamin D deficient (11-32 ng/ml) postmenopausal breast cancer patients undergoing adjuvant AI therapy. The proposed clinical trial aims to evaluate the efficacy of: 1) high-dose vitamin D supplementation, 2) high-dose vitamin D supplementation plus an individually tailored home-based weight-bearing aerobic (walking) and progressive resistance exercise program, compared to 3) low-dose vitamin D supplementation on bone metabolism and bone mineral density. Data provided will support a more definitive phase III clinical trial and potentially inform the practice of evidence-based medicine for the treatment of CTIBL. Dr. Peppone will use the training and data obtained by this award to develop into an independent clinical researcher in the cancer control field.

描述（由申请人提供）：癌症流行病学家M.P.H. Luke Peppone博士正在申请指导的职业发展奖，以扩大他的研究技能，并成为癌症控制中的独立临床研究者，重点是开发和测试干预措施，以治疗癌症治疗诱发的癌症诱发的骨质流失（CTIBL）。该提案将评估旨在防止芳香酶抑制剂（AI）治疗引起的绝经后乳腺癌患者CTIBL的干预措施，这导致骨质流失2至4倍，并显着增加该人群的骨折风险。该研究项目将使补充高剂量维生素D的功效以及一个个性化的体重锻炼计划，以防止CTIBL。职业发展计划：Peppone博士以前是专门研究癌症的流行病学家的经验，再加上他作为临床癌症控制研究人员的持续培训，使他非常适合成为一名独立研究人员，专注于CTIBL的发病机理和治疗。他的培训目标将扩大他的知识，并将其分为三个培训目标：1）在生物学，生理学，遗传学和CTIBL的测量中发展专业知识，2）2）在设计，行为和分析II/III期随机对照临床试验的设计，行为和分析方面的PI经验，以及在营养临床的测试和行为方面的经验（以营养为行为）（行为）（行为）的经验（ ctibl。过去三十年来，领先的癌症控制研究员加里·莫罗（Gary Morrow）博士将担任Peppone博士的首席高级导师，并提供 临床试验领域的指导。兰迪·罗西尔（Randy Rosier）博士和顾问Alissa Huston博士将在CTIBL的生物学，生理学和促成因素方面提供专业知识。玛丽·里德（Mary Reid）博士和顾问唐纳德·特朗普（Donald Trump）博士在维生素D的疗效和药理学方面为CTIBL管理提供了经验，而Co-Enctoror Karen Mustian博士将培训Peppone博士为CTIBL开发和实施锻炼干预措施。顾问Godfrey博士将提供遗传分析的培训，顾问Heckler博士将提供统计培训。研究计划：基于生物学的合理性和可行性数据，提出的试点RCT是一项三臂研究，该研究测试了预防癌症治疗诱导的105个中度维生素D缺乏症（11-32 ng/mL）的两种干预措施，后者是苏联治疗后辅助癌症患者治疗的绝经后乳腺癌后患者。拟议的临床试验旨在评估：1）高剂量维生素D补充，2）高剂量维生素D补充补充以及单独定制的基于家庭的重量有氧运动（步行）和进行性耐药性运动，与3）相比，与3）低剂量的维生素D补充了骨代谢和骨骼矿物质的低剂量维生素D。提供的数据将支持更确切的III期临床试验，并有可能为CTIBL治疗的循证医学实践提供信息。 Peppone博士将使用该奖项获得的培训和数据将其发展为癌症控制领域的独立临床研究人员。