A Pilot Clinical Trial of Paricalcitol for Chronic Pancreatitis

帕立骨化醇治疗慢性胰腺炎的初步临床试验

• 批准号: 10709481
• 负责人: Marc T Goodman
• 金额: $ 30.07万
• 依托单位: CEDARS-SINAI MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10709481
• 关键词: Abdominal Pain; Afferent Neurons; Alcohol abuse; Animal Model; Appointment; Area; Attenuated; Biological; Biological Markers; Cancer Etiology; Cell secretion; Cessation of life; Clinical; Clinical Trials; Collection; Conduct Clinical Trials; Cytoplasm; DNA Sequence Alteration; Data; Desmoplastic; Development; Diabetes Mellitus; Disease; Disease Progression; Double-Blind Method; Drug Screening; Enrollment; Ensure; Environment; Evaluation; Exocrine pancreas; Extracellular Matrix Proteins; FDA approved; Failure; Fatality rate; Fibrosis; Future; Genes; Genomics; Goals; High Fat Diet; Image; Inflammatory; Intervention; Letters; Lipids; Liquid substance; Longitudinal cohort study; Macrophage; Malignant Neoplasms; Malignant neoplasm of pancreas; Measurement; Measures; Mediating; Medical Surveillance; Monitor; Myeloid Cells; Outcome; Pain; Pancreas; Pancreatic Diseases; Pancreatic enzyme; Pancreatitis; Participant; Patient Outcomes Assessments; Patient Recruitments; Patients; Pilot Projects; Placebo Control; Placebos; Process; Production; Prospective, cohort study; Quality of life; Randomized; Recurrence; Research; Research Design; Resources; Risk Factors; Schools; Signal Transduction; Smoking; Social Functioning; Specimen; Surrogate Markers; Symptoms; TGFB1 gene; Testing; Therapeutic; Time; Tissues; Transforming Growth Factor beta; Validation; Vitamin A; Vitamin D; Vitamin D Analog; Vitamin D3 Receptor; Work; acute pancreatitis; analog; biomarker discovery; cell type; chemotherapeutic agent; chronic pain; chronic pancreatitis; clinical development; clinical outcome measures; cohort; cytokine; double-blind placebo controlled trial; epidemiology study; feasibility testing; follow-up; health related quality of life; high risk; imaging biomarker; improved; improved outcome; pain reduction; pancreatic stellate cell; paricalcitol; participant enrollment; patient population; pilot trial; pre-clinical; prevent; prospective; recruit; reduce symptoms; response; response biomarker; safety and feasibility; stellate cell; symptomatic improvement; therapeutically effective; therapy development; translational study; treatment duration; treatment response

ABSTRACT The primary objective of the proposed trial is to examine the feasibility of testing the effect of a potent vitamin D analogue, paricalcitol, on health-related quality of life (HRQoL), and imaging and liquid biomarkers in patients with chronic pancreatitis (CP). If determined feasible, subsequent trials will be developed that focus on the efficacy of paricalcitol in improving outcomes in CP. Tragically, pain has the most important influence on diminished HRQoL and increased resource utilization in pancreatitis patients. Development of clinical trials in CP patients to improve treatment options, attenuate symptoms, and prevent exocrine function failure, diabetes and pancreatic cancer is widely considered an area of enormous unmet need. There is a substantial body of preclinical evidence that potent vitamin D analogues have significant and beneficial effects on both pancreatitis and pancreatic cancer by blocking Transforming Growth Factor Beta (TGFβ) signaling and reducing pain. We hypothesize that paricalcitol treatment will improve symptoms, as measured by patient reported HRQoL, and normalize imaging and liquid biomarkers of the pancreatic fibro-inflammatory process in this high-risk patient population. Because surrogate biomarkers of response to therapeutics have not been developed for CP, early trials such as this one are needed to assist with biomarker discovery for future validation. We propose a pilot randomized double-blind, placebo-controlled trial to evaluate the feasibility and safety of a 12-month paricalcitol intervention versus placebo administration. We will collect measures of HRQoL, and changes in measures (imaging and liquid) of the fibro-inflammatory response. We will randomize 24 CP patients 1:1 to paricalcitol vs placebo with a 21-month recruitment period and a one-year follow-up period. Importantly, our efficient study design will enroll patients who are participants in our ongoing prospective longitudinal cohort study, PROCEED (PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies), which is conducted under the auspices of the US Consortium on Chronic Pancreatitis, Diabetes and Pancreatic Cancer (CPDPC). Nesting in the PROCEED study provides a well-defined clinical cohort of patients who are under frequent medical surveillance allowing us to harmonize patient recruitment, collection of biological specimens, and follow-up with routine clinical and research appointments and tests, ensuring high rates of recruitment and retention. Feasibility will be met if the proportion of patients who enroll and complete the 12 months of paricalcitol therapy is ≥75% of planned. Importantly, this trial will provide a platform for study design and measurements needed for implementation of potential treatment agents for CP.

抽象的 该试验的主要目的是检查测试A的效果的可行性 有效的维生素D模拟，副醇，与健康相关的生活质量（HRQOL）以及成像和液体 慢性胰腺炎患者（CP）的生物标志物。如果确定可行，随后的试验将是 开发着侧重于副醇在改善CP结局中的效率。可悲的是，疼痛有 对胰腺炎中HRQOL减少和资源利用率增加的最重要影响 患者。开发CP患者的临床试验以改善治疗选择，减轻症状， 并防止外分泌功能衰竭，糖尿病和胰腺癌被广泛认为是 巨大的未满足需求。有大量的临床前证据表明潜在的维生素D 类似物通过阻塞对胰腺炎和胰腺癌具有重大且有益的影响 转化生长因子β（TGFβ）信号传导和减轻疼痛。 我们假设二核酸治疗将改善症状，如患者报道的 HRQOL并将胰腺纤维炎症过程的成像和液体生物标志物归一化 这个高风险的患者人群。因为对治疗反应的替代生物标志物尚未 是针对CP开发的，需要进行诸如此类的早期试验以协助生物标志物发现 未来验证。我们提出了一项飞行员随机双盲，安慰剂对照试验，以评估 与安慰剂给药的12个月间cor醇干预的可行性和安全性。我们将 收集HRQOL的度量，以及纤维炎症的度量（成像和液体）的变化 回复。我们将在21个月的招聘中将24名CP患者随机1：1与副醇与安慰剂进行 期间和一年的随访期。重要的是，我们有效的研究设计将招募患者 是我们正在进行的前瞻性纵向队列研究的参与者，继续进行（前瞻性 评估流行病学和转化研究的慢性胰腺炎），这是进行的） 在美国慢性胰腺炎，糖尿病和胰腺癌的主持下 （CPDPC）。筑巢研究中的研究提供了明确定义的临床队列 在经常的医疗监视下，我们可以协调患者招聘，收集生物学 标本，并随访常规临床和研究任命和测试，以确保高率 招募和保留。如果注册和完成的患者比例 12个月的二核治疗≥75％的计划。重要的是，该试验将提供一个平台 用于实施CP潜在治疗剂所需的研究设计和测量。