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: 10447175
• 负责人: Kenneth Cusi
• 金额: $ 45.57万
• 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/10447175
• 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; Role; Sampling; Study Subject; Technology; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Trials; 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; drug repurposing; 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; risk stratification; sarcopenia; surgery outcome; therapeutically effective; 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.

CPDPC的继续将需要完成受试者的获取，并 生物标本，并进行充分的随访，以确定临床相关的结果。未来努力 包括生物标志物的开发和验证，药物 开发或再利用，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、危险分层和精确治疗。第二个临床需求是开发 更好的治疗与胰腺疾病相关的糖尿病，更好的管理 胰腺疾病本身。我们建议在下一阶段进行一项生物标志物研究， CPDPC是一项将肌肉减少症作为慢性骨关节炎患者预后不良生物标志物的研究， 胰腺炎我们还建议在CPDPC的下一阶段进行2项潜在试验， 开发更有效的治疗胰源性（3c型）糖尿病的方法， 评估疼痛性慢性胰腺炎的手术干预时机： 1.完成PROCEED、DETECT和NOD队列的招募和随访，以及 纳入战略，以增加非正规就业受试者的招聘。招聘，保留， 所有队列的高质量数据将需要继续。征兵 NOD协议是最具挑战性的。我们将利用OneFlorida的临床数据 研究网络，以确定合作伙伴的健康组织在佛罗里达，以增加 NOD以及未来临床试验中合格研究受试者的汇总。 2.描述急性肌肉减少症患者的患病率、预测因素和影响， 复发性胰腺炎和慢性胰腺炎，以及与共存的相互作用 糖尿病;并建立策略，以确定和治疗这些患者的肌肉减少症。 虽然肌肉减少症已被确定为胰腺癌的常见后果， 慢性胰腺炎患者肌肉减少症的患病率和临床影响是 同等临床意义。 3.在CPDPC内实施临床试验，评估手术干预的时机 疼痛性慢性胰腺炎或复发性胰腺炎患者。疼痛是最 慢性胰腺炎的常见症状，最常见的干预原因， 也是生活质量最重要的贬低者。医疗、内窥镜和手术 治疗不是非常有效，最佳干预的选择和时机 结果尚不清楚。一项比较手术治疗（引流或 切除术）与内窥镜治疗相比， 不依赖阿片类药物，并且没有出现持续疼痛， 更有效的治疗时机。 4.确定胰源性胰腺炎最有效和最安全的管理策略 慢性胰腺炎患者患有糖尿病（3c型）。这些人混合了 胰岛素抵抗和胰岛素缺乏，并可能营养不良。缺乏 胰岛细胞反调节激素使治疗引起的低血糖 一个非常显著的风险，胰腺外分泌功能不全的共存可能 营养吸收更难预测。我们建议对患者进行横断面分析， 进入PROCEED和DETECT队列，随后进行两种治疗的试验 方法（当前的标准医学治疗与新可用的设备， 连续葡萄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乏的关键领域：肌肉减少症在 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，以及复杂代谢特征的管理 3C型糖尿病这些潜在的项目，如果通过继续执行《方案》， 将适当地利用第一次迭代的CPDPC和 临床中心的平台，以实现CPDPC的原始目标和目的。