U-01 CONSORTIUM FOR THE STUDY OF CHRONIC PANCREATITIS,DIABETES AND PANCREATIC CANCER CLINICAL CENTERS

U-01 慢性胰腺炎、糖尿病和胰腺癌临床中心研究联盟

• 批准号: 10263499
• 负责人: Kenneth Cusi
• 金额: $ 9.04万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-28 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10263499
• 关键词: Acute; Adopted; Anatomy; Area; Biological; Biological Markers; Cancer Patient; Cancer Prognosis; Chronic; Clinical; Clinical Cancer Center; Clinical Data; Clinical Research; Clinical Trials; Complex; Cross-Sectional Studies; Data; Development; Devices; Diabetes Mellitus; Disease; Drainage procedure; Early Diagnosis; Excision; Exocrine pancreatic insufficiency; Florida; Future; Glucose; Goals; Health system; Hormones; Hypoglycemia; Image; Individual; Insulin; Insulin Resistance; Insulin deficiency; Intervention; Intervention Trial; Islet Cell; Islets of Langerhans; Knowledge; Lead; Malignant neoplasm of pancreas; Malnutrition; Measures; Medical; Morbidity - disease rate; Operative Surgical Procedures; Opiate Addiction; Opioid; Outcome; Pain; Pain management; Pancreas; Pancreatic Diseases; Pancreatitis; Patients; Phase; Precision therapeutics; Prevalence; Prevention; Protocols documentation; Quality of life; Relapse; Research; Resources; Risk; Risk Factors; Risk stratification; Role; Sampling; Study Subject; Technology; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Trials; Treatment Efficacy; Universities; Work; accurate diagnosis; acute pancreatitis; biomarker development; biomarker validation; central sensitization; chronic pain; chronic pancreatitis; clinical center; clinically relevant; cohort; common symptom; diabetes mellitus therapy; drug development; effective intervention; effective therapy; follow-up; glucose monitor; glycemic control; health organization; high risk; improved; improved outcome; individual patient; member; metabolic profile; mortality; negative affect; novel marker; nutrient absorption; personalized approach; personalized screening; precision medicine; prevent; recruit; response; sarcopenia; surgery outcome; treatment risk; trial comparing

The continuation of the CPDPC will require the completion of the acquisition of subjects and biospecimens, and sufficient follow-up to determine clinically relevant outcomes. Future efforts for which the CPDPC was formed include includes biomarker development and validation, drug development or repurposing, and therapeutic trials. Biomarker development and validation is needed for such purposes as early diagnosis (chronic pancreatitis and pancreatic cancer), prognosis, risk stratification and precision therapy. A second clinical need is the development of better therapies for the diabetes associated with pancreatic diseases, and better management of the pancreatic diseases themselves. We propose one biomarker study for the next phase of the CPDPC, a study of sarcopenia as a biomarker for worse outcome in patients with chronic pancreatitis. We also propose 2 potential trials for the next phase of the CPDPC, one focused on developing more effective therapy for pancreaticogenic (Type 3c) diabetes and one for a trial assessing timing of surgical intervention in painful chronic pancreatitis: 1. Finalize recruitment and follow-up of the PROCEED, DETECT, and NOD cohorts, and incorporate strategies to increase recruitment of NOD subjects. Recruitment, retention, and high quality data will need to be continued for all the cohorts. Recruitment into the NOD protocol has been most challenging. We will utilize the OneFlorida clinical data research network to identify partner health organizations within Florida to increase the pool of eligible study subjects in both NOD as well as future clinical trials. 2. Characterize the prevalence, predictors, and impact of sarcopenia in patients with acute relapsing pancreatitis and chronic pancreatitis, and the interaction with coexistent diabetes; and establish strategies to identify and treat sarcopenia in these patients. While sarcopenia has been identified as a common consequence of pancreatic cancer, the prevalence of sarcopenia and clinical impact in patients with chronic pancreatitis is of equal clinical import. 3. Implement a clinical trial within the CPDPC assessing the timing of surgical intervention in patients with painful chronic pancreatitis or relapsing pancreatitis. Pain is the most common symptom from chronic pancreatitis, the most common reason for intervention, and the most important detractor from quality of life. Medical, endoscopic, and surgical therapy are not highly effective, and the choice and timing of intervention for best outcomes is not known. A trial comparing outcomes from surgical therapy (drainage or resection) compared to endoscopic therapy in individuals with suitable anatomy who are not dependent on opioids and have not developed continuous pain is likely to identify more effective timing of therapy. 4. Determine the most effective and safest management strategy for pancreaticogenic diabetes (Type 3c) in patients with chronic pancreatitis. These individuals have a mix of insulin resistance and insulin deficiency, and may be malnourished. The lack of pancreatic islet cell counterregulatory hormones make treatment-induced hypoglycemia a very significant risk, and the coexistence of exocrine pancreatic insufficiency may nutrient absorption less predictable. We propose a cross sectional analysis of patients entered into PROCEED and DETECT cohorts, followed by a trial of two treatment approaches (current standard medical therapy, versus newly available devices for continuous glucose monitoring and insulin therapy) to determine the most effective and safest strategies. This proposed work spans critical areas of knowledge deficit: the role of sarcopenia in chronic pancreatitis and relapsing acute pancreatitis, the most effective use of interventional therapy for chronic pancreatitis pain, and the management of the complex metabolic profiles of Type3c diabetes. These potential projects, if adopted by the continuation of the CPDPC, will appropriately utilize the resources generated by the first iteration of the CPDPC and the platform of clinical centers to realize the original goals and objectives of the CPDPC.

国家方案和方案的延续将需要完成对科目的购置和 生物制品，以及充分的随访以确定临床相关的结果。未来的努力 CPDPC的成立包括生物标记物的开发和验证，药物 开发或改变用途，以及治疗试验。生物标志物的开发和验证是 需要用于早期诊断(慢性胰腺炎和胰腺癌)， 预后、危险分层和精准治疗。第二个临床需要是发展 更好地治疗与胰腺疾病相关的糖尿病，以及更好的管理 胰腺疾病本身。我们建议进行下一阶段的生物标志物研究 CPDPC是一项关于骨质疏松症作为慢性阻塞性肺疾病患者预后不良的生物标志物的研究 胰腺炎。我们还为CPDPC的下一阶段提出了两项潜在的试验，一项重点是 关于开发更有效的治疗胰源性(3c型)糖尿病的方法和一项试验 评估痛性慢性胰腺炎的手术干预时机： 1.最后确定继续、发现和点头队列的招募和后续行动，以及 纳入战略，增加NOD科目的招聘。招聘、留住、 而且所有队列的高质量数据都需要继续下去。招募入职人员 NOD协议一直是最具挑战性的。我们将利用One佛罗里达州的临床数据 研究网络，以确定佛罗里达州的合作伙伴卫生组织，以增加 NOD和未来临床试验中符合条件的研究对象池。 2.描述急性骨质疏松症患者骨质疏松症的患病率、预测因素和影响 复发性胰腺炎与慢性胰腺炎及其共存的相互作用 糖尿病；并制定策略，以识别和治疗这些患者的石棺减少症。 虽然石棺减少已被确认为胰腺癌的常见后果， 慢性胰腺炎患者的骨钙素减少的发生率和临床影响是 同等的临床重要性。 3.在CPDPC内实施临床试验，评估手术干预的时机 用于疼痛的慢性胰腺炎或复发性胰腺炎患者。最痛的是 慢性胰腺炎的常见症状，这是干预的最常见原因， 也是对生活质量最重要的诋毁者。内科、内窥镜和外科 治疗效果不是很好，而介入的选择和时机是最好的 结果尚不清楚。一项比较手术治疗(引流或引流)结果的试验 与内窥镜治疗相比，具有合适的解剖结构的患者 不依赖阿片类药物和没有出现持续性疼痛可能会被识别为 更有效的治疗时机。 4.确定最有效、最安全的胰腺癌治疗策略 慢性胰腺炎患者的糖尿病(3c型)。这些人有混合的 胰岛素抵抗和胰岛素缺乏，并可能是营养不良。缺乏 胰岛细胞逆调节激素治疗引起的低血糖 一种非常重大的风险，并伴有胰腺外分泌功能不全可能 养分吸收的可预测性较差。我们建议对患者进行横断面分析。 进入继续和检测队列，随后进行两个治疗的试验 方法(目前的标准药物治疗，与新推出的设备相比 连续血糖监测和胰岛素治疗)，以确定最有效和 最安全的策略。 这项拟议的工作跨越了知识缺失的关键领域：骨质疏松症在 慢性胰腺炎和复发性急性胰腺炎最有效的介入治疗 慢性胰腺炎疼痛的治疗和复杂代谢谱的处理 3c型糖尿病。这些潜在的项目，如果被国家发改委继续通过， 将适当利用CPDPC第一次迭代产生的资源和 临床中心的平台，以实现CPDPC最初的目标和目标。