口服精氨酸形式的代谢命运的表征
具有与代谢综合征相关的风险因素的健康受试者中口服 L-精氨酸形式的代谢命运的表征。
研究概览
详细说明
该研究是一项随机交叉研究,包括 16 名具有代谢综合征危险因素的健康受试者和 16 名健康对照受试者。 根据双交叉设计,每个受试者随机接受两种口服形式的 L-精氨酸(A 和 B),并在精氨酸给药的第一天和补充这种精氨酸形式一周后参加探索日。 两周的精氨酸补充被至少2周的清除期隔开。
第一次精氨酸剂量给药后,每次探索都持续 24 小时以上。 在第一次给药后的 0、0.5、1、2、4、6、8、12、16、24 小时进行血液检查。 在补充期后的探索期间,我们还收集了尿液(第一次给药后 0、2、4、8、12、24 小时)。
研究类型
注册 (实际的)
阶段
- 不适用
联系人和位置
学习地点
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Ile-de-France
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Bobigny、Ile-de-France、法国、93000
- Centre de Recherche sur Volontaires (CRV), Hospital Avicenne
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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
描述
患有“高甘油三酯血症腰”的健康受试者:
纳入标准:
- 年龄介乎18至60岁
- 超重(BMI 在 25 至 30 公斤/平方米之间)
- “高甘油三酯血症腰围”(男性腰围 > 94 厘米或女性腰围 > 88 厘米且空腹甘油三酯水平 > 150 毫克/分升)
排除标准:
- 肥胖症(BMI> 30 公斤/平方米)
- 心脏或血管疾病
- 糖尿病
- 甲状腺疾病
- 收缩压 > 150 mmHg 或舒张压 > 90 mmHg
- 烟草消费 > 每周 6 支香烟
- 饮酒量> 每天 3 杯
- 任何药物(避孕药治疗除外)或膳食补充剂摄入量不能在研究期间首次就诊前一周停止。
- 被监护人
- 怀孕(阳性 β-hCG 血液检测)
- 阳性血清学 HBsAg AcHbc、HCV 和 HIV
- 血红蛋白 < 14 g/dl(男性)或 <12 g/dl(女性)
- 参加研究前 6 个月内的临床试验
健康对照对象:
纳入标准:
- 年龄介乎18至60岁
- 正常体重(BMI 在 18.5 和 25 kg/m² 之间)
- 男性腰围 < 94 厘米或女性腰围 < 88 厘米且空腹甘油三酯水平 < 150 毫克/分升
排除标准 :
- 心脏或血管疾病
- 糖尿病
- 甲状腺疾病
- 收缩压 > 150 mmHg 或舒张压 > 90 mmHg
- 烟草消费 > 每周 6 支香烟
- 饮酒量> 每天 3 杯
- 任何药物(避孕药治疗除外)或膳食补充剂摄入量不能在研究期间首次就诊前一周停止。
- 被监护人
- 怀孕(阳性 β-hCG 血液检测)
- 阳性血清学 HBsAg AcHbc、HCV 和 HIV
- 血红蛋白 < 14 g/dl(男性)或 <12 g/dl(女性)
- 参加研究前 6 个月内的临床试验
学习计划
研究是如何设计的?
设计细节
- 分配:随机化
- 介入模型:交叉作业
- 屏蔽:单身的
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:患有“高甘油三酯血症腰部”的健康受试者
超重、腰围升高和空腹甘油三酯血症升高的受试者。 干预:A 型精氨酸和 B 型精氨酸 |
3 粒胶囊,含 0.5 克 A 型 L-精氨酸(1.5 克),每天 3 次(每天 4.5 克),持续 1 周
3 粒胶囊,含 0.5 克 B 型 L-精氨酸(1.5 克),每天 3 次(每天 4.5 克),持续 1 周
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实验性的:健康受试者
对照受试者,即没有超重、腰围升高和空腹甘油三酯血症升高。 干预:A 型精氨酸和 B 型精氨酸 |
3 粒胶囊,含 0.5 克 A 型 L-精氨酸(1.5 克),每天 3 次(每天 4.5 克),持续 1 周
3 粒胶囊,含 0.5 克 B 型 L-精氨酸(1.5 克),每天 3 次(每天 4.5 克),持续 1 周
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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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估计一剂口服精氨酸转化为 NO 的总转化率
大体时间:每次治疗在补充前(第 0 天)和补充后(第 8 天)24 小时重复测量
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该评估使用标记的精氨酸([15N2-(胍基)]-精氨酸)作为早上服用的第一剂精氨酸,并测量 24 小时尿液中的 15NO3。 在给予 15N-精氨酸后,对于每次尿液收集,我们确定硝酸盐排泄(通过反应化学发光测量利尿和硝酸盐浓度)和硝酸根离子同位素 15N 富集(通过微扩散技术和连接到同位素质谱仪 EA 的元素分析仪-IRMS),根据同位素稀释原理,确定摄入的精氨酸中硝酸盐的总量。 这种排泄量相对于摄入剂量的总和决定了摄入的精氨酸向 NO 的相对转化率。 |
每次治疗在补充前(第 0 天)和补充后(第 8 天)24 小时重复测量
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24 小时内血浆精氨酸浓度动力学曲线的估计
大体时间:每次治疗在补充前(第 0 天)和补充后(第 8 天)24 小时重复测量
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如前所述(Haque 等人,2012 年),使用超高效液相色谱-质谱系统测定血浆 AA 浓度。
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每次治疗在补充前(第 0 天)和补充后(第 8 天)24 小时重复测量
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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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内皮功能血浆标志物的定量分析
大体时间:每次治疗的补充前(第 0 天)和补充后(第 8 天)
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血管细胞粘附分子-1 (VCAM-1)、细胞间粘附分子 (ICAM-1)、E-选择素、P-选择素、纤溶酶原激活物抑制剂-1 (PAI-1) 的空腹血浆浓度将使用两种自定义方法测定带有抗体包被珠子的混合检测试剂盒,使用 Luminex xMAP 技术平台进行免疫化学生物检测的多重分析。 此外,我们还有亚硝酸盐的血浆浓度,NO 产生的标志物(通过反应化学发光)和其他相关标志物(3-硝基酪氨酸、亚硝基硫醇、cGMP,特别是 ANP,通过免疫化学)。 |
每次治疗的补充前(第 0 天)和补充后(第 8 天)
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精氨酸用于 NO 和尿素合成的动力学估计
大体时间:每次治疗补充后(第 8 天)重复测量 24 小时
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施用 15N-精氨酸后,我们测量了精氨酸和瓜氨酸(通过质谱联用气相色谱法)、血浆和尿素(通过分离、离子交换和 EA-IRMS)以及血浆和尿素中的尿液浓度。 这些数据以及精氨酸和瓜氨酸浓度的那些数据,通过同位素稀释原理,提供了摄入的精氨酸的血浆外观及其以 NO 合酶和精氨酸酶方式代谢的产物的血浆外观和尿液排泄。 然后对这些数据进行分区建模工作,以这些方式建立代谢流。 |
每次治疗补充后(第 8 天)重复测量 24 小时
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其他定量分析
大体时间:每次治疗的补充前(第 0 天)和补充后(第 8 天)
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每次治疗的补充前(第 0 天)和补充后(第 8 天)
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合作者和调查者
调查人员
- 首席研究员:Robert Benamouzig、Hospital AVICENNE
- 研究主任:François Mariotti, PhD、AgroParisTech
出版物和有用的链接
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A型精氨酸的临床试验
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Rio de Janeiro State UniversityUniversidade Federal Fluminense; Rio de Janeiro State Research Supporting Foundation (FAPERJ)招聘中
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University of Southern DenmarkEsbjerg Municipality; Municipality of Slagelse; Municipality of Odense; Christian Albrechts Universität... 和其他合作者完全的