利西拉来对 2 型糖尿病患者和健康人胃排空和血压下降的药物试验 (Lixi)
利西拉来对 2 型糖尿病和健康受试者的胃排空、血糖和“餐后”血压的影响。
研究概览
详细说明
利西拉来是一种已被证明可以降低 2 型糖尿病患者餐后血糖的药物,现已获准在澳大利亚使用。 尽管胃排空减慢可能是利西拉来降低餐后餐后血糖的主要机制,但利西拉来对胃排空的影响迄今尚未通过闪烁显像的“金标准”技术进行量化。 该研究将首次确定和评估利西拉来对血糖的影响程度以及利西拉来对血糖的影响与闪烁显像对胃排空影响之间的关系。 该信息对于有效使用利西拉来治疗患有餐后低血压的 2 型糖尿病患者具有重要意义。
餐后低血压是一种重要的临床疾病,经常发生在老年人和 2 型糖尿病患者身上,目前的管理并不理想。 虽然介导餐后低血压的机制知之甚少,但内脏血流调节受损、胃扩张、小肠分娩率以及神经和激素机制已被确定为可能的病理生理机制。 膳食摄入与内脏血液汇集和随之而来的静脉血液回流减少有关。 在具有完整压力反射机制的健康年轻人和老年人中,这些变化会导致心率、心搏量和心输出量增加,从而导致血压代偿性升高。 但是,对于餐后低血压患者,这些反应不足以维持血压。 当胃排空更快时,血压下降的幅度更大,胃排空减慢可以显着减弱健康老年受试者和 2 型患者的餐后血压下降。
目前没有关于利西拉来对2型糖尿病患者餐后血压和内脏血流影响的信息。
本研究的目的是确定利西拉来是否减少餐后血压下降以及胃排空对血压、心率和内脏血流量的相关影响。
缺乏利西拉来对食欲和能量摄入的影响以及这些与胃排空作用的关系。
假设利西拉来会减缓口服葡萄糖的胃排空;减弱空腹和餐后血糖升高;减轻血压下降的幅度、心率升高和 SMA 流量增加,减少饥饿感,增加饱腹感并减少自助餐时的能量摄入,对 2 型糖尿病患者的影响比健康受试者更大。
研究类型
注册 (预期的)
阶段
- 阶段2
- 阶段1
联系人和位置
学习联系方式
- 姓名:Rachael S Tippett, BSc Honours
- 电话号码:2915 8222 2915
- 邮箱:rachael.tippett@adelaide.edu.au
研究联系人备份
- 姓名:Laurence G Trahair, BHlthSci Hon
- 电话号码:2915 8222 2915
- 邮箱:laurence.trahair@adelaide.edu.au
学习地点
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South Australia
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Adelaide、South Australia、澳大利亚、5000
- 招聘中
- Discipline of Medicine, Royal Adelaide Hospital
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接触:
- Karen L Jones, PhD
- 电话号码:25394 +61 8 8222 5394
- 邮箱:karen.jones@adelaide.edu.au
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接触:
- Michael Horowitz, PhD, FRACP
- 电话号码:24327 +61 8 8222 4327
- 邮箱:michael.horowitz@adelaide.edu.au
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首席研究员:
- Karen L Jones, PhD
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副研究员:
- Laurence G Trahair, BHlthSci Hon
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副研究员:
- Rachael S Tippett, BSc Honours
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副研究员:
- Chris Rayner, PhD, FRACP
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副研究员:
- Michael Horowitz, PhD, FRACP
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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
纳入标准:
健康科目:
- 男性或女性(使用适当避孕方法或愿意接受妊娠试验的女性)
- 身体质量指数 (BMI) 19 - 30 公斤/平方米
2 型糖尿病患者:
- 根据“健康受试者”
- 仅通过饮食或二甲双胍控制的 2 型糖尿病(世界卫生组织 (WHO) 标准)
- 糖化血红蛋白 >6.0% 且 <8.5%
排除标准:
有严重呼吸系统疾病、心血管疾病、肝脏疾病和/或肾脏疾病病史的受试者(严重的是该疾病的社会或身体表现,或患有该病症,对个人正常生活的能力产生负面和显着影响日常生活)、长期酗酒或癫痫(病史除外)或铁状态或肝功能检查超出以下范围:
- 丙氨酸转氨酶 (ALT) 0 - 55 U/L
- 碱性磷酸酶 30 - 110 U/L
- 天冬氨酸转氨酶 0 - 45 U/L
- 淀粉酶和/或脂肪酶 >3 x ULN
- 胆红素 6 - 24 毫摩尔/升
- 铁蛋白 15 - 200 ng/mL(女性); 30 - 300 纳克/毫升(男性)
- 血红蛋白 115 - 155 g/L(女性); 135 - 172 克/升(雄性)
- 肌酐清除率临界值 <50 ml/min 的受试者
- 需要可能影响血压或胃肠功能的药物治疗的受试者
- 有胃肠道疾病病史的受试者,包括已知的胃轻瘫、明显的上消化道症状和既往胃手术史
- 有不明原因胰腺炎、慢性胰腺炎、胰腺切除术病史的受试者
- 当前或既往有 c 细胞癌病史的受试者
- 吸烟 > 10 支香烟/天
- 饮酒量 > 20 克/天
- 在过去 12 周内献过血的受试者
- 没有有效避孕方法的育龄妇女(定义为绝经前,筛选前至少 3 个月未手术绝育的妇女)必须在筛选访问时确认尿液 B-hCG 妊娠试验阴性。 他们还必须在整个研究过程中使用有效的避孕方法,并同意在指定的访问中重复进行尿妊娠试验。
- 哺乳期
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:跨界
- 屏蔽:双倍的
武器和干预
参与者组/臂 |
干预/治疗 |
---|---|
ACTIVE_COMPARATOR:利西拉来
利西拉来:10 mcg,一次皮下注射剂量
|
腹腔给药
其他名称:
|
PLACEBO_COMPARATOR:安慰剂
匹配安慰剂:一次皮下注射剂量
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腹腔给药
其他名称:
|
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 |
---|---|---|
血压
大体时间:每项研究 4.5 小时
|
收缩压和舒张压 (mmHg)
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每项研究 4.5 小时
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
心率
大体时间:每项研究 4.5 小时
|
心率(每分钟心跳次数)
|
每项研究 4.5 小时
|
胃排空率
大体时间:每项研究 3 小时
|
胃潴留(占整个胃的百分比)
|
每项研究 3 小时
|
血糖浓度
大体时间:每项研究 3 小时
|
血糖(毫摩尔/升)
|
每项研究 3 小时
|
其他结果措施
结果测量 |
措施说明 |
大体时间 |
---|---|---|
胃内分布
大体时间:每项研究 3 小时
|
近端和远端胃的滞留百分比
|
每项研究 3 小时
|
胃肠道激素释放(GLP-1、GIP、C 肽和 3-OMG 的浓度)
大体时间:每项研究 4.5 小时
|
GLP-1、GIP、C 肽和 3-OMG 的浓度
|
每项研究 4.5 小时
|
肠系膜上动脉血流量
大体时间:每项研究 3.5 小时
|
多普勒超声(毫升/分钟)
|
每项研究 3.5 小时
|
食欲(视觉模拟问卷)
大体时间:每项研究 4.5 小时
|
饥饿感、饱腹感、食欲 (mm)
|
每项研究 4.5 小时
|
心输出量
大体时间:每项研究 3.5 小时
|
Finapres (大)
|
每项研究 3.5 小时
|
每搏量
大体时间:每项研究 3.5 小时
|
Finapres (大)
|
每项研究 3.5 小时
|
合作者和调查者
调查人员
- 首席研究员:Karen L Jones, PhD、University of Adelaide, Royal Adelaide Hospital
出版物和有用的链接
一般刊物
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- Stevens JE, Horowitz M, Deacon CF, Nauck M, Rayner CK, Jones KL. The effects of sitagliptin on gastric emptying in healthy humans - a randomised, controlled study. Aliment Pharmacol Ther. 2012 Aug;36(4):379-90. doi: 10.1111/j.1365-2036.2012.05198.x. Epub 2012 Jun 28.
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- Jones KL, Tonkin A, Horowitz M, Wishart JM, Carney BI, Guha S, Green L. Rate of gastric emptying is a determinant of postprandial hypotension in non-insulin-dependent diabetes mellitus. Clin Sci (Lond). 1998 Jan;94(1):65-70. doi: 10.1042/cs0940065.
- Gentilcore D, Bryant B, Wishart JM, Morris HA, Horowitz M, Jones KL. Acarbose attenuates the hypotensive response to sucrose and slows gastric emptying in the elderly. Am J Med. 2005 Nov;118(11):1289. doi: 10.1016/j.amjmed.2005.05.019. No abstract available.
- Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31-41. doi: 10.1159/000180580.
- Schirra J, Houck P, Wank U, Arnold R, Goke B, Katschinski M. Effects of glucagon-like peptide-1(7-36)amide on antro-pyloro-duodenal motility in the interdigestive state and with duodenal lipid perfusion in humans. Gut. 2000 May;46(5):622-31. doi: 10.1136/gut.46.5.622.
- Brennan IM, Feltrin KL, Horowitz M, Smout AJ, Meyer JH, Wishart J, Feinle-Bisset C. Evaluation of interactions between CCK and GLP-1 in their effects on appetite, energy intake, and antropyloroduodenal motility in healthy men. Am J Physiol Regul Integr Comp Physiol. 2005 Jun;288(6):R1477-85. doi: 10.1152/ajpregu.00732.2004. Epub 2005 Feb 3.
- Little TJ, Pilichiewicz AN, Russo A, Phillips L, Jones KL, Nauck MA, Wishart J, Horowitz M, Feinle-Bisset C. Effects of intravenous glucagon-like peptide-1 on gastric emptying and intragastric distribution in healthy subjects: relationships with postprandial glycemic and insulinemic responses. J Clin Endocrinol Metab. 2006 May;91(5):1916-23. doi: 10.1210/jc.2005-2220. Epub 2006 Feb 21.
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- Riddle M, Home P, Marre M, Niemoeller E, Ping L, Rosenstock J. Efficacy and safety of once-daily lixisenatide in type 2 diabetes insufficiently controlled with basal insulin ± metformin: GetGoal-L Study. Diabetes 2012;61(Suppl 1):A212-A344 (Abstract 983-P).
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- Ratner R, Hanefield M, Shamanna P, et al. Efficacy and safety of lixisenatide once daily versus placebo in patients with T2DM insufficiently controlled on sulfonylurea + metformin (GetGoal-S). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1):1-542 (Abstract 785).
- Pinget M, Goldenberg R, Niemoeller E, Muehlen-Bartmer I, Guo H, Aronson R. Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (GetGoal-P). Diabetes Obes Metab. 2013 Nov;15(11):1000-7. doi: 10.1111/dom.12121. Epub 2013 May 26.
- Rosenstock J, Raccah D, Koranyi L, et al. Efficacy and safety of lixisenatide once daily versus exenatide twice daily in patients with T2DM insufficiently controlled on metformin (GetGoal-X). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1):1-542 (Abstract 786).
- Bolli G, Munteanu M, Dotsenko S, Niemoeller E, Boka G, Hanefield M. Efficacy and safety of lixisenatide once-daily versus placebo in patients with T2DM insufficiently controlled on metformin (GetGoal-F1). Poster presented at 47th Annual Meeting of the European Association for the Study of Diabetes, 12-16 September 2011, Lisbon, Portugal. Diabetologia 2011;54(Suppl 1): 1-542 (Abstract 784).
- Fonseca VA, Alvarado-Ruiz R, Raccah D, Boka G, Miossec P, Gerich JE; EFC6018 GetGoal-Mono Study Investigators. Efficacy and safety of the once-daily GLP-1 receptor agonist lixisenatide in monotherapy: a randomized, double-blind, placebo-controlled trial in patients with type 2 diabetes (GetGoal-Mono). Diabetes Care. 2012 Jun;35(6):1225-31. doi: 10.2337/dc11-1935. Epub 2012 Mar 19.
- Meier JJ, Kemmeries G, Holst JJ, Nauck MA. Erythromycin antagonizes the deceleration of gastric emptying by glucagon-like peptide 1 and unmasks its insulinotropic effect in healthy subjects. Diabetes. 2005 Jul;54(7):2212-8. doi: 10.2337/diabetes.54.7.2212.
- Christensen M, Knop FK, Vilsboll T, Holst JJ. Lixisenatide for type 2 diabetes mellitus. Expert Opin Investig Drugs. 2011 Apr;20(4):549-57. doi: 10.1517/13543784.2011.562191. Epub 2011 Mar 11.
- Shannon JR, Diedrich A, Biaggioni I, Tank J, Robertson RM, Robertson D, Jordan J. Water drinking as a treatment for orthostatic syndromes. Am J Med. 2002 Apr 1;112(5):355-60. doi: 10.1016/s0002-9343(02)01025-2.
- Vanis L, Gentilcore D, Lange K, Gilja OH, Rigda RS, Trahair LG, Feinle-Bisset C, Rayner CK, Horowitz M, Jones KL. Effects of variations in intragastric volume on blood pressure and splanchnic blood flow during intraduodenal glucose infusion in healthy older subjects. Am J Physiol Regul Integr Comp Physiol. 2012 Feb 15;302(4):R391-9. doi: 10.1152/ajpregu.00464.2011. Epub 2011 Nov 30.
- O'Donovan D, Feinle C, Tonkin A, Horowitz M, Jones KL. Postprandial hypotension in response to duodenal glucose delivery in healthy older subjects. J Physiol. 2002 Apr 15;540(Pt 2):673-9. doi: 10.1113/jphysiol.2001.013442.
- Mathias CJ. Postprandial hypotension. Pathophysiological mechanisms and clinical implications in different disorders. Hypertension. 1991 Nov;18(5):694-704. doi: 10.1161/01.hyp.18.5.694. No abstract available.
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- Barragan JM, Rodriguez RE, Eng J, Blazquez E. Interactions of exendin-(9-39) with the effects of glucagon-like peptide-1-(7-36) amide and of exendin-4 on arterial blood pressure and heart rate in rats. Regul Pept. 1996 Nov 14;67(1):63-8. doi: 10.1016/s0167-0115(96)00113-9.
- White J. Efficacy and safety of incretin based therapies: clinical trial data. J Am Pharm Assoc (2003). 2009 Sep-Oct;49 Suppl 1:S30-40. doi: 10.1331/JAPhA.2009.09079.
- Jones KL, MacIntosh C, Su YC, Wells F, Chapman IM, Tonkin A, Horowitz M. Guar gum reduces postprandial hypotension in older people. J Am Geriatr Soc. 2001 Feb;49(2):162-7. doi: 10.1046/j.1532-5415.2001.49037.x.
- Gentilcore D, Nair NS, Vanis L, Rayner CK, Meyer JH, Hausken T, Horowitz M, Jones KL. Comparative effects of oral and intraduodenal glucose on blood pressure, heart rate, and splanchnic blood flow in healthy older subjects. Am J Physiol Regul Integr Comp Physiol. 2009 Sep;297(3):R716-22. doi: 10.1152/ajpregu.00215.2009. Epub 2009 Jun 24.
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- Marathe CS, Pham H, Wu T, Trahair LG, Rigda RS, Buttfield MDM, Hatzinikolas S, Lange K, Rayner CK, Mari A, Horowitz M, Jones KL. Acute Administration of the GLP-1 Receptor Agonist Lixisenatide Diminishes Postprandial Insulin Secretion in Healthy Subjects But Not in Type 2 Diabetes, Associated with Slowing of Gastric Emptying. Diabetes Ther. 2022 Jun;13(6):1245-1249. doi: 10.1007/s13300-022-01258-4. Epub 2022 Apr 22.
研究记录日期
研究主要日期
学习开始
初级完成 (预期的)
研究完成 (预期的)
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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