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

CPDPC 的继续将需要完成科目和 生物样本，以及足够的随访以确定临床相关结果。未来的努力 CPDPC 成立的目的包括生物标志物开发和验证、药物 开发或重新利用以及治疗试验。生物标志物的开发和验证是 早期诊断（慢性胰腺炎和胰腺癌）等目的所需的， 预后、风险分层和精准治疗。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以及更好的管理 胰腺疾病本身。我们建议下一阶段进行一项生物标志物研究 CPDPC，一项将肌肉减少症作为慢性病患者预后较差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 2 项可能的试验，其中一项重点关注 开发更有效的胰源性（3c 型）糖尿病治疗方法并进行试验 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 纳入增加 NOD 受试者招募的策略。招聘、保留、 所有队列都需要继续提供高质量的数据。招聘进入 NOD 协议最具挑战性。我们将利用 OneFlorida 临床数据 研究网络确定佛罗里达州内的合作健康组织，以增加 NOD 以及未来临床试验中合格的研究对象库。 2. 描述急性肌少症患者的患病率、预测因素和影响 复发性胰腺炎和慢性胰腺炎，以及两者共存的相互作用 糖尿病；并制定识别和治疗这些患者肌肉减少症的策略。 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及其临床影响 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 患有疼痛性慢性胰腺炎或复发性胰腺炎的患者。痛苦是最大的 慢性胰腺炎的常见症状，最常见的干预原因， 也是影响生活质量的最重要因素。医疗、内窥镜和外科 治疗的效果并不高，干预的选择和时机是最佳的 结果未知。一项比较手术治疗（引流或 切除术）与具有合适解剖结构的个体的内窥镜治疗相比 不依赖阿片类药物且未出现持续疼痛可能会被识别 更有效的治疗时机。 4. 确定最有效、最安全的胰源性治疗策略 慢性胰腺炎患者的糖尿病（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导致治疗引起的低血糖 一个非常重大的风险，并且外分泌胰腺功能不全的共存可能 营养吸收不太可预测。我们建议对患者进行横断面分析 进入 PROCEED 和 DETECT 队列，然后进行两种治疗试验 方法（当前的标准药物治疗，与新可用的设备相比 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匮乏的关键领域：肌肉减少症在 慢性胰腺炎和复发性急性胰腺炎，介入治疗最有效 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被 CPDPC 的延续所采纳， 将适当利用 CPDPC 第一次迭代和 临床中心平台，以实现CPDPC的最初目的和目标。

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.