DELTA F508 CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 这是一项I期、开放标签、安全性和剂量探索研究，在患有囊性纤维化的成人受试者中口服姜黄素类药物，这些受试者是？F508 CFTR突变。 本研究的主要目的是评估安全性的推进剂量的姜黄素口服管理连续14天的成人受试者囊性纤维化（CF）谁是纯合子？F508 CFTR。 本研究的次要目的是：1）获得CF受试者中口服姜黄素的药代动力学数据，2）通过测量鼻电位差（NPD）评估姜黄素改变跨呼吸道上皮细胞离子转运的功效，3）通过测量汗液氯化物浓度初步评估姜黄素改变跨汗腺导管上皮细胞离子转运的潜在功效。 该研究是非随机化和开放标签的，没有安慰剂对照。 它将由一个14天给药队列组成，其中初始剂量水平将给药7天，随后是更高剂量水平给药7天。 该队列将入组约10例受试者，以达到总计8例可评价受试者。 本研究将涉及2家临床试验机构。 受试者将连续7天接受1.5 g研究药物每日三次（TID）（剂量水平1），随后连续7天接受3 g研究药物TID（剂量水平2）。 每例受试者参与研究的时间约为34天，包括5次研究访视，定义为：访视1（筛选，第-14天至第-10天，其中第1天是受试者将接受首次研究药物给药的日期），访视2（基线测量和开始研究药物，第1天）、访视3（开始较高剂量，第8天）、访视4（研究药物末次给药，第15天）和访视5（随访，第22天）。 研究药物将在访视2（第1天）下午以初始剂量水平首次给药。受试者将于第1天晚上在家中服用研究药物，第2天至第7天每天三次，上午、下午和晚上。 将在访视3（第8天）早晨给予初始剂量水平的研究药物末次给药。 研究药物将在访视3（第8天）下午以较高剂量水平给药。 受试者将于第8天晚上在家中接受较高剂量水平的研究药物，第9天至第14天每天3次。 较高剂量水平的最终剂量将在访视4（第15天）早晨给药。 受试者可选择在访视3和访视4前在研究中心GCRC过夜，以便在这些早晨的适当时间（上午8点）开始访视程序开始。 本研究将评估安全性参数的变化，以及筛选访视（访视1）、第8天（访视3，初始剂量水平末次给药后）和第15天（访视4，研究药物末次给药后）访视之间鼻电位差（NPD）测量值的变化。 将在访视1（筛选）或访视2给药前或访视1和2之间的任何一天获得基线汗液氯化物测量结果。 将在访视4研究药物末次给药后进行治疗后汗液氯化物测量。在访视2（第1天）研究药物首次给药前采集血浆用于基线药代动力学（PK）分析。 将在访视2研究药物首次给药后、访视3（第8天）研究药物末次以初始剂量水平给药后和访视4（第15天）研究药物末次以较高剂量水平给药后进行连续PK采集。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. This is a Phase I, open label, safety and dose finding study of advancing doses of orally administered curcuminoids in adult subjects with cystic fibrosis who are homozygous for ?F508 CFTR mutation. The primary objective of this study is to assess the safety of advancing doses of curcuminoids administered orally for fourteen consecutive days in adult subjects with cystic fibrosis (CF) who are homozygous for ?F508 CFTR. The secondary objectives of this study are: 1) to obtain pharmacokinetic data for oral curcuminoids in CF subjects, 2) to assess the efficacy of curcuminoids to alter ion transport across respiratory epithelia by measurement of nasal potential difference (NPD), and 3) to make a preliminary assessment of the potential efficacy of curcuminoids to alter ion transport across sweat duct epithelia by measurement of sweat chloride concentrations. The study is non-randomized and open label with no placebo control. It will consist of a single 14-day dosing cohort in which an initial dose level will be administered for 7 days, followed by a higher dose level administered for 7 days. Approximately 10 subjects will be enrolled in the cohort in order to achieve a total of 8 evaluable subjects. Two (2) sites will be involved in the study. Subjects will receive 1.5 grams of study drug three times per day (TID) (Dose Level 1) for 7 consecutive days, followed by 3 grams of study drug TID (Dose Level 2) for 7 consecutive days. The length of study participation for each subject will be approximately 34 days and consist of 5 study Visits defined as: Visit 1 (Screening, Day -14 to -10 where Day 1 is that day on which the subject will receive their first dose of study drug), Visit 2 (Baseline measurements and initiation of study drug, Day 1), Visit 3 (Initiation of higher dose, Day 8), Visit 4 (final dose of study drug, Day 15), and Visit 5 (Follow-up, Day 22). Study drug will first be administered at the initial dose level in the afternoon at Visit 2 (Day 1). The subject will take study drug at home on the evening of Day 1 and three times a day, morning, afternoon and evening, on Days 2 through 7. The final dose of study drug at the initial dose level will be administered on the morning of Visit 3 (Day 8). Study drug will be administered at the higher dose level in the afternoon at Visit 3 (Day 8). The subject will take study drug at the higher dose level at home on the evening of Day 8 and three times a day on Days 9 through 14. The final dose at the higher dose level will be administered in the morning at Visit 4 (Day 15). Subjects will be allowed the option of staying in the site GCRC overnight prior to Visits 3 and 4 to allow the Visit procedures to begin at an appropriate time on those mornings (@ 8am). The study will assess changes in safety parameters, and changes in Nasal Potential Difference (NPD) measurements between Visits at screening (Visit 1), Day 8 (Visit 3, after final dose at initial dose level) and Day 15 (Visit 4, after the final dose of study drug). A baseline sweat chloride measurement will be obtained at Visit 1 (screening), or at Visit 2 prior to dosing, or any day between Visits 1 and 2. A post-treatment sweat chloride measurement will be performed on Visit 4 following the final dose of study drug. A plasma collection will be obtained for baseline pharmacokinetic (PK) analysis at Visit 2 (Day 1) prior to the first dose of study drug. Sequential PK collections will be obtained following the first dose of study drug on Visit 2, following the last administration of study drug at the initial dose level on Visit 3 (Day 8), and following the last administration of study drug at the higher dose level on Visit 4 (Day 15).