多中心围手术期阿片类药物遗传学研究
预测儿童围手术期阿片类药物不良反应和个性化镇痛:一项多中心药物遗传学研究
研究概览
地位
条件
详细说明
阿片类药物作为一个群体在缓解疼痛方面经受住了时间的考验。 吗啡是最常用的“黄金标准”阿片类药物,用于控制手术疼痛。 与其他阿片类药物一样,吗啡具有较窄的治疗指数和较大的患者间反应差异性。 某些遗传和非遗传因素被认为是导致吗啡镇痛反应和副作用变化的原因。 决定个体疼痛敏感性和调节吗啡药代动力学(转运蛋白)和药效学(受体和信号转导元件)的遗传因素可能是造成这种变异性的原因。 不幸的是,镇痛反应的频繁变化在临床上具有重要意义,其中一端的疼痛缓解不充分,另一端的主要副作用包括由于相对过量而导致的潜在致命的呼吸抑制。 外科手术后对吗啡剂量的个体间差异大部分可以通过编码参与疼痛感知、阿片类药物转运和阿片类药物受体信号转导的蛋白质的基因子集中的单核苷酸多态性 (SNP) 来解释。 μ阿片受体 (OPRM1)、儿茶酚-O-甲基转移酶 (COMT)、多药耐药转运蛋白基因 ABC B1 的遗传变异已在小型成人研究中与不同程度的疼痛敏感性、对阿片类药物的镇痛反应和易感性相关联阿片类药物的严重副作用,如呼吸抑制、镇静和呕吐。 由于对疼痛的感知和对阿片类药物的反应经常发生临床变化,因此在临床上很难有效和安全地缓解一部分儿童的急性术后疼痛。 据研究者所知,没有其他研究试图对儿童围手术期镇痛进行个体化。 研究人员的长期目标是确定改变疼痛敏感性和对吗啡反应的因素,以便开发更有效、更安全和量身定制的疗法。 本申请的总体目标是评估 OPRM1、COMT 和 ABC B1 基因中遗传多态性的个体和组合影响的贡献,以及它们与术后疼痛缓解和吗啡不良反应的关联。 研究人员的中心假设是,参与疼痛感知、阿片类药物转运和阿片类药物受体信号通路的基因中的特定遗传多态性对儿童的疼痛敏感性、吗啡消耗量和吗啡副作用有显着影响。
本研究还将探索一组可能影响儿童对吗啡的痛觉和反应的其他重要 SNP。 将根据疼痛评分、吗啡剂量、吗啡副作用的发生率(包括呼吸抑制、镇静、呕吐和瘙痒)对数据进行分析。
研究类型
注册 (实际的)
联系人和位置
学习地点
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California
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Los Angeles、California、美国、90027
- Children's Hospital Of Los Angeles
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Palo Alto、California、美国、94304
- Stanford University Medical Center
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Colorado
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Denver、Colorado、美国、80045
- The Children's Hospital, Denver
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Florida
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Miami、Florida、美国、33136
- University of Miami - Miller School of Medicine
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Illinois
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Chicago、Illinois、美国、60614
- Children's Memorial Hospital
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Louisiana
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New Orleans、Louisiana、美国、70121
- Ochsner Medical Center for Children
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Maryland
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Baltimore、Maryland、美国、21287
- The Johns Hopkins Hospital
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Massachusetts
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Boston、Massachusetts、美国、02115
- Boston Children's Hospital
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Michigan
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Ann Arbor、Michigan、美国、48109
- C.S. Mott Children's Hospital
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Missouri
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St. Louis、Missouri、美国、63110
- St. Louis Children's Hospital
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Ohio
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Cincinnati、Ohio、美国、45229
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19134
- St. Christopher's Hospital for Children
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Texas
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Houston、Texas、美国、77094
- Texas Children's Hospital
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Washington
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Seattle、Washington、美国、98105
- Seattle Children's Hospital
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Wisconsin
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Madison、Wisconsin、美国、53792
- UW Health-American Family Children's Hospital
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
取样方法
研究人群
描述
纳入标准:
- 6-17岁的儿童
- ASA 身体状况 1 和 2
- 计划进行扁桃体切除术 (T) 以及扁桃体切除术和腺样体切除术 (T 和 A)
- 患有阻塞性睡眠呼吸暂停的儿童也将包括在内。
排除标准:
- 发育迟缓的儿童
- 肝脏和肾脏疾病,
- 需要止痛药的术前疼痛(例如 慢性扁桃体炎)。
学习计划
研究是如何设计的?
设计细节
研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
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安全成果
大体时间:麻醉后恢复室,预计平均2小时
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恢复室中严重阿片类药物相关不良反应的发生率,包括呼吸抑制、过度镇静、恶心和呕吐。
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麻醉后恢复室,预计平均2小时
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
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疗效结果测量 - 阿片类药物干预
大体时间:麻醉后恢复室,预计平均2小时
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恢复室所需的阿片类药物干预次数
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麻醉后恢复室,预计平均2小时
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疗效结果测量 - 阿片类药物需求
大体时间:麻醉后恢复室,预计平均2小时
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将测量阿片类药物的总需求量
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麻醉后恢复室,预计平均2小时
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疗效结果测量 - 疼痛评分
大体时间:麻醉后恢复室,预计平均2小时
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通过数字评定量表 (NRS) 和面部表情、腿部运动、活动、哭泣和可安慰性 (FLACC) 量表测量的疼痛评分
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麻醉后恢复室,预计平均2小时
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合作者和调查者
合作者
调查人员
- 首席研究员:Senthilkumar Sadhasivam、Children's Hospital Medical Center, Cincinnati
出版物和有用的链接
一般刊物
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研究记录日期
研究主要日期
学习开始 (实际的)
初级完成 (实际的)
研究完成
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (估计)
上次提交的符合 QC 标准的更新
最后验证
更多信息
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