替米沙坦预防异基因造血干细胞移植后急性GVHD的研究
2026年3月20日 更新者:Hackensack Meridian Health
替米沙坦 (Micardis) 预防异基因造血干细胞移植后急性移植物抗宿主病的初步研究
这是一项关于替米沙坦预防急性 GVHD 的单中心、开放标签、前瞻性研究,研究对象为大约 60 名接受同种异体 HCT 治疗血液恶性肿瘤的受试者。
研究概览
详细说明
这是一项关于替米沙坦预防急性 GVHD 的单中心、开放标签、前瞻性研究,研究对象为大约 60 名接受同种异体 HCT 治疗血液恶性肿瘤的受试者。
受试者将在 HCT 前 2 天(第 -2 天)开始每天一次接受 160 mg Micardis 牌替米沙坦。
一旦患者在 HCT 后出院,治疗将持续到 HCT 后第 +98 天,共计 101 天。
在 HCT 后第 +98 天或之前停止治疗后,将对受试者进行长达 6 个月的主要和次要终点随访。
研究类型
介入性
注册 (实际的)
32
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息,以及有关进行该研究的地点的信息。
学习地点
-
-
New Jersey
-
Hackensack、New Jersey、美国、07601
- Hackensack University Medical Center
-
-
参与标准
研究人员寻找符合特定描述的人,称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 99年 (成人、年长者)
接受健康志愿者
不
描述
纳入标准:
诊断:
- 缓解期的急性髓性或淋巴性白血病,
- 骨髓增生异常综合症,
- 慢性淋巴细胞白血病,
- 非霍奇金淋巴瘤,
- 霍奇金淋巴瘤,
- 处于慢性或加速期的慢性粒细胞白血病,
- 骨髓增生性疾病,或
- 多发性骨髓瘤
- 接受来自相关或无关供体的同种异体 HSC 移植,在 HLA-A、-B、-C 和 DR 基因座的 8 个中至少有 7 个匹配(“8/8”或“7/8”匹配)
在基于清髓性 TBI、白消安或(非清髓性)美法仑的移植前预处理方案后接受同种异体 HSC 移植。 移植方案将包括以下药物之一,与氟达拉滨或环磷酰胺联合给药:
- 白消安 130 mg/m2 每天静脉注射 x 2(降低强度)或 4 天
- TBI 150 cGy bid x8 剂量 (1200 Gy)
- 马法兰 140 毫克/平方米。 (虽然美法仑不是清髓性治疗方案,但它会导致临床上显着的粘膜炎,接受这种药物治疗的患者将对这些数据的分析产生相当大的兴趣。)
- 18 岁或以上的男性或女性患者
- Karnofsky 表现状态 > 70% 在移植前调节开始时
- 移植前调节开始时移植特异性合并症评分 <5
- 服用抗高血压药物(包括替米沙坦)的患者符合条件,但患者必须在首次服用研究药物前至少 48 小时停止治疗
- 能够给予知情同意并签署知情同意书
排除标准:
- 无法提供知情同意
- 患有已知心力衰竭、需要肾脏替代治疗的晚期肾功能不全或肝功能衰竭的受试者,尽管这些患者很可能不符合 HCT 的条件。
- 服用 ACE 抑制剂、钾补充剂或螺内酯(或任何其他保钾利尿剂)且在研究治疗开始前不能停止使用或需要高钾饮食的受试者
- 患者在开始替米沙坦前两天因医疗或其他原因无法停用目前的高血压药物
- 慢性症状性低血压,血容量不足。
学习计划
本节提供研究计划的详细信息,包括研究的设计方式和研究的衡量标准。
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:不适用
- 介入模型:单组作业
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的:160 毫克替米沙坦
60 名患者将接受 160 片替米沙坦(2 片 80 毫克片剂),持续 101 天
|
其他名称:
|
研究衡量的是什么?
主要结果指标
结果测量 |
大体时间 |
|---|---|
|
接受同种异体 HCT 的患者中患有 3 级或以上急性移植物抗宿主病 (GVHD) 的受试者数量。
大体时间:移植后100天
|
移植后100天
|
次要结果测量
结果测量 |
大体时间 |
|---|---|
|
根据国家癌症研究所通用术语,患有 III-IV 级低血压的受试者数量
大体时间:移植后180天
|
移植后180天
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 首席研究员:Scott Rowley, MD、Hackensack Meridian Health
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Brunstein CG, Miller JS, Cao Q, McKenna DH, Hippen KL, Curtsinger J, Defor T, Levine BL, June CH, Rubinstein P, McGlave PB, Blazar BR, Wagner JE. Infusion of ex vivo expanded T regulatory cells in adults transplanted with umbilical cord blood: safety profile and detection kinetics. Blood. 2011 Jan 20;117(3):1061-70. doi: 10.1182/blood-2010-07-293795. Epub 2010 Oct 15.
- Penack O, Socie G, van den Brink MR. The importance of neovascularization and its inhibition for allogeneic hematopoietic stem cell transplantation. Blood. 2011 Apr 21;117(16):4181-9. doi: 10.1182/blood-2010-10-312934. Epub 2011 Jan 21.
- Przepiorka D, Weisdorf D, Martin P, Klingemann HG, Beatty P, Hows J, Thomas ED. 1994 Consensus Conference on Acute GVHD Grading. Bone Marrow Transplant. 1995 Jun;15(6):825-8.
- Marshall JC, Foster D, Vincent JL, Cook DJ, Cohen J, Dellinger RP, Opal S, Abraham E, Brett SJ, Smith T, Mehta S, Derzko A, Romaschin A; MEDIC study. Diagnostic and prognostic implications of endotoxemia in critical illness: results of the MEDIC study. J Infect Dis. 2004 Aug 1;190(3):527-34. doi: 10.1086/422254. Epub 2004 Jul 2.
- Vander Lugt MT, Braun TM, Hanash S, Ritz J, Ho VT, Antin JH, Zhang Q, Wong CH, Wang H, Chin A, Gomez A, Harris AC, Levine JE, Choi SW, Couriel D, Reddy P, Ferrara JL, Paczesny S. ST2 as a marker for risk of therapy-resistant graft-versus-host disease and death. N Engl J Med. 2013 Aug 8;369(6):529-39. doi: 10.1056/NEJMoa1213299.
- Blazar BR, Murphy WJ, Abedi M. Advances in graft-versus-host disease biology and therapy. Nat Rev Immunol. 2012 May 11;12(6):443-58. doi: 10.1038/nri3212.
- Fricke WF, Maddox C, Song Y, Bromberg JS. Human microbiota characterization in the course of renal transplantation. Am J Transplant. 2014 Feb;14(2):416-27. doi: 10.1111/ajt.12588. Epub 2013 Dec 26.
- Hill GR, Ferrara JL. The primacy of the gastrointestinal tract as a target organ of acute graft-versus-host disease: rationale for the use of cytokine shields in allogeneic bone marrow transplantation. Blood. 2000 May 1;95(9):2754-9.
- Chen X, Dodge J, Komorowski R, Drobyski WR. A critical role for the retinoic acid signaling pathway in the pathophysiology of gastrointestinal graft-versus-host disease. Blood. 2013 May 9;121(19):3970-80. doi: 10.1182/blood-2012-08-445130. Epub 2013 Mar 25.
- Wolf D, von Lilienfeld-Toal M, Wolf AM, Schleuning M, von Bergwelt-Baildon M, Held SA, Brossart P. Novel treatment concepts for graft-versus-host disease. Blood. 2012 Jan 5;119(1):16-25. doi: 10.1182/blood-2011-08-339465. Epub 2011 Sep 26.
- Choi S, Reddy P. Graft-versus-host disease. Panminerva Med. 2010 Jun;52(2):111-24.
- Ringden O, Shrestha S, da Silva GT, Zhang MJ, Dispenzieri A, Remberger M, Kamble R, Freytes CO, Gale RP, Gibson J, Gupta V, Holmberg L, Lazarus H, McCarthy P, Meehan K, Schouten H, Milone GA, Lonial S, Hari PN. Effect of acute and chronic GVHD on relapse and survival after reduced-intensity conditioning allogeneic transplantation for myeloma. Bone Marrow Transplant. 2012 Jun;47(6):831-7. doi: 10.1038/bmt.2011.192. Epub 2011 Sep 26.
- Lee SJ, Klein JP, Barrett AJ, Ringden O, Antin JH, Cahn JY, Carabasi MH, Gale RP, Giralt S, Hale GA, Ilhan O, McCarthy PL, Socie G, Verdonck LF, Weisdorf DJ, Horowitz MM. Severity of chronic graft-versus-host disease: association with treatment-related mortality and relapse. Blood. 2002 Jul 15;100(2):406-14. doi: 10.1182/blood.v100.2.406.
- Signori A, Crocchiolo R, Oneto R, Sacchi N, Sormani MP, Fagioli F, Rambaldi A, Ciceri F, Bacigalupo A. Chronic GVHD is associated with lower relapse risk irrespective of stem cell source among patients receiving transplantation from unrelated donors. Bone Marrow Transplant. 2012 Nov;47(11):1474-8. doi: 10.1038/bmt.2012.58. Epub 2012 Apr 2.
- Patterson AE, Korngold R. Infusion of select leukemia-reactive TCR Vbeta+ T cells provides graft-versus-leukemia responses with minimization of graft-versus-host disease following murine hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2001;7(4):187-96. doi: 10.1053/bbmt.2001.v7.pm11349805.
- Fanning SL, Zilberberg J, Stein J, Vazzana K, Berger SA, Korngold R, Friedman TM. Unraveling graft-versus-host disease and graft-versus-leukemia responses using TCR Vbeta spectratype analysis in a murine bone marrow transplantation model. J Immunol. 2013 Jan 1;190(1):447-57. doi: 10.4049/jimmunol.1201641. Epub 2012 Nov 30.
- Komanduri KV. Targeting neovascularization in GVHD. Blood. 2013 Apr 25;121(17):3303-4. doi: 10.1182/blood-2013-01-480483.
- Leonhardt F, Grundmann S, Behe M, Bluhm F, Dumont RA, Braun F, Fani M, Riesner K, Prinz G, Hechinger AK, Gerlach UV, Dierbach H, Penack O, Schmitt-Graff A, Finke J, Weber WA, Zeiser R. Inflammatory neovascularization during graft-versus-host disease is regulated by alphav integrin and miR-100. Blood. 2013 Apr 25;121(17):3307-18. doi: 10.1182/blood-2012-07-442665. Epub 2013 Jan 17.
- Penack O, Henke E, Suh D, King CG, Smith OM, Na IK, Holland AM, Ghosh A, Lu SX, Jenq RR, Liu C, Murphy GF, Lu TT, May C, Scheinberg DA, Gao DC, Mittal V, Heller G, Benezra R, van den Brink MR. Inhibition of neovascularization to simultaneously ameliorate graft-vs-host disease and decrease tumor growth. J Natl Cancer Inst. 2010 Jun 16;102(12):894-908. doi: 10.1093/jnci/djq172. Epub 2010 May 12.
- Petrovic A, Alpdogan O, Willis LM, Eng JM, Greenberg AS, Kappel BJ, Liu C, Murphy GJ, Heller G, van den Brink MR. LPAM (alpha 4 beta 7 integrin) is an important homing integrin on alloreactive T cells in the development of intestinal graft-versus-host disease. Blood. 2004 Feb 15;103(4):1542-7. doi: 10.1182/blood-2003-03-0957. Epub 2003 Oct 16.
- Reshef R, Luger SM, Hexner EO, Loren AW, Frey NV, Nasta SD, Goldstein SC, Stadtmauer EA, Smith J, Bailey S, Mick R, Heitjan DF, Emerson SG, Hoxie JA, Vonderheide RH, Porter DL. Blockade of lymphocyte chemotaxis in visceral graft-versus-host disease. N Engl J Med. 2012 Jul 12;367(2):135-45. doi: 10.1056/NEJMoa1201248.
- Engelhardt BG, Jagasia M, Savani BN, Bratcher NL, Greer JP, Jiang A, Kassim AA, Lu P, Schuening F, Yoder SM, Rock MT, Crowe JE Jr. Regulatory T cell expression of CLA or alpha(4)beta(7) and skin or gut acute GVHD outcomes. Bone Marrow Transplant. 2011 Mar;46(3):436-42. doi: 10.1038/bmt.2010.127. Epub 2010 May 31.
- Engelhardt BG, Sengsayadeth SM, Jagasia M, Savani BN, Kassim AA, Lu P, Shyr Y, Yoder SM, Rock MT, Crowe JE Jr. Tissue-specific regulatory T cells: biomarker for acute graft-vs-host disease and survival. Exp Hematol. 2012 Dec;40(12):974-982.e1. doi: 10.1016/j.exphem.2012.08.002. Epub 2012 Aug 10.
- Liu Z, Zhao Y, Wei F, Ye L, Lu F, Zhang H, Diao Y, Song H, Qi Z. Treatment with telmisartan/rosuvastatin combination has a beneficial synergistic effect on ameliorating Th17/Treg functional imbalance in hypertensive patients with carotid atherosclerosis. Atherosclerosis. 2014 Mar;233(1):291-9. doi: 10.1016/j.atherosclerosis.2013.12.004. Epub 2014 Jan 10.
- Mihaescu A, Santen S, Jeppsson B, Thorlacius H. Rho kinase signalling mediates radiation-induced inflammation and intestinal barrier dysfunction. Br J Surg. 2011 Jan;98(1):124-31. doi: 10.1002/bjs.7279. Epub 2010 Sep 29.
- Arab HH, Al-Shorbagy MY, Abdallah DM, Nassar NN. Telmisartan attenuates colon inflammation, oxidative perturbations and apoptosis in a rat model of experimental inflammatory bowel disease. PLoS One. 2014 May 15;9(5):e97193. doi: 10.1371/journal.pone.0097193. eCollection 2014.
- Kobayashi N, Ohno T, Yoshida K, Fukushima H, Mamada Y, Nomura M, Hirata H, Machida Y, Shinoda M, Suzuki N, Matsuoka H. Cardioprotective mechanism of telmisartan via PPAR-gamma-eNOS pathway in dahl salt-sensitive hypertensive rats. Am J Hypertens. 2008 May;21(5):576-81. doi: 10.1038/ajh.2008.27. Epub 2008 Mar 20.
- Iyengar S, Zhan C, Lu J, Korngold R, Schwartz DH. Treatment with a rho kinase inhibitor improves survival from graft-versus-host disease in mice after MHC-haploidentical hematopoietic cell transplantation. Biol Blood Marrow Transplant. 2014 Aug;20(8):1104-11. doi: 10.1016/j.bbmt.2014.04.029. Epub 2014 May 2.
- Song EK, Yim JM, Yim JY, Song MY, Rho HW, Yim SK, Jeon SY, Kim HS, Yhim HY, Lee NR, Kwak JY, Sohn MH, Park HS, Jang KY, Yim CY. Rosiglitazone prevents graft-versus-host disease (GVHD). Transpl Immunol. 2012 Oct;27(2-3):128-37. doi: 10.1016/j.trim.2012.09.001. Epub 2012 Sep 13.
- Walcher D, Hess K, Heinz P, Petscher K, Vasic D, Kintscher U, Clemenz M, Hartge M, Raps K, Hombach V, Marx N. Telmisartan inhibits CD4-positive lymphocyte migration independent of the angiotensin type 1 receptor via peroxisome proliferator-activated receptor-gamma. Hypertension. 2008 Feb;51(2):259-66. doi: 10.1161/HYPERTENSIONAHA.107.099028. Epub 2007 Dec 24.
- Cianchetti S, Del Fiorentino A, Colognato R, Di Stefano R, Franzoni F, Pedrinelli R. Anti-inflammatory and anti-oxidant properties of telmisartan in cultured human umbilical vein endothelial cells. Atherosclerosis. 2008 May;198(1):22-8. doi: 10.1016/j.atherosclerosis.2007.09.013. Epub 2007 Oct 22.
- Siragusa M, Sessa WC. Telmisartan exerts pleiotropic effects in endothelial cells and promotes endothelial cell quiescence and survival. Arterioscler Thromb Vasc Biol. 2013 Aug;33(8):1852-60. doi: 10.1161/ATVBAHA.112.300985. Epub 2013 May 23.
- Usui T, Sugisaki K, Iriyama A, Yokoo S, Yamagami S, Nagai N, Ishida S, Amano S. Inhibition of corneal neovascularization by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci. 2008 Oct;49(10):4370-6. doi: 10.1167/iovs.07-0964.
- Nagai N, Noda K, Urano T, Kubota Y, Shinoda H, Koto T, Shinoda K, Inoue M, Shiomi T, Ikeda E, Tsubota K, Suda T, Oike Y, Ishida S. Selective suppression of pathologic, but not physiologic, retinal neovascularization by blocking the angiotensin II type 1 receptor. Invest Ophthalmol Vis Sci. 2005 Mar;46(3):1078-84. doi: 10.1167/iovs.04-1101.
- Riento K, Ridley AJ. Rocks: multifunctional kinases in cell behaviour. Nat Rev Mol Cell Biol. 2003 Jun;4(6):446-56. doi: 10.1038/nrm1128.
- Yoneda A, Multhaupt HA, Couchman JR. The Rho kinases I and II regulate different aspects of myosin II activity. J Cell Biol. 2005 Aug 1;170(3):443-53. doi: 10.1083/jcb.200412043. Epub 2005 Jul 25.
- Wang Y, Zheng XR, Riddick N, Bryden M, Baur W, Zhang X, Surks HK. ROCK isoform regulation of myosin phosphatase and contractility in vascular smooth muscle cells. Circ Res. 2009 Feb 27;104(4):531-40. doi: 10.1161/CIRCRESAHA.108.188524. Epub 2009 Jan 8.
- Vicari RM, Chaitman B, Keefe D, Smith WB, Chrysant SG, Tonkon MJ, Bittar N, Weiss RJ, Morales-Ballejo H, Thadani U; Fasudil Study Group. Efficacy and safety of fasudil in patients with stable angina: a double-blind, placebo-controlled, phase 2 trial. J Am Coll Cardiol. 2005 Nov 15;46(10):1803-11. doi: 10.1016/j.jacc.2005.07.047. Epub 2005 Oct 19.
- Shimokawa H, Hiramori K, Iinuma H, Hosoda S, Kishida H, Osada H, Katagiri T, Yamauchi K, Yui Y, Minamino T, Nakashima M, Kato K. Anti-anginal effect of fasudil, a Rho-kinase inhibitor, in patients with stable effort angina: a multicenter study. J Cardiovasc Pharmacol. 2002 Nov;40(5):751-61. doi: 10.1097/00005344-200211000-00013.
- Fukumoto Y, Mohri M, Inokuchi K, Ito A, Hirakawa Y, Masumoto A, Hirooka Y, Takeshita A, Shimokawa H. Anti-ischemic effects of fasudil, a specific Rho-kinase inhibitor, in patients with stable effort angina. J Cardiovasc Pharmacol. 2007 Mar;49(3):117-21. doi: 10.1097/FJC.0b013e31802ef532.
- Otsuka T, Ibuki C, Suzuki T, Ishii K, Kodani E, Atarashi H, Kishida H, Takano T. Vasodilatory effect of subsequent administration of fasudil, a rho-kinase inhibitor, surpasses that of nitroglycerin at the concentric coronary stenosis in patients with stable angina pectoris. Circ J. 2006 Apr;70(4):402-8. doi: 10.1253/circj.70.402.
- Masumoto A, Mohri M, Shimokawa H, Urakami L, Usui M, Takeshita A. Suppression of coronary artery spasm by the Rho-kinase inhibitor fasudil in patients with vasospastic angina. Circulation. 2002 Apr 2;105(13):1545-7. doi: 10.1161/hc1002.105938.
- Mohri M, Shimokawa H, Hirakawa Y, Masumoto A, Takeshita A. Rho-kinase inhibition with intracoronary fasudil prevents myocardial ischemia in patients with coronary microvascular spasm. J Am Coll Cardiol. 2003 Jan 1;41(1):15-9. doi: 10.1016/s0735-1097(02)02632-3.
- Inokuchi K, Ito A, Fukumoto Y, Matoba T, Shiose A, Nishida T, Masuda M, Morita S, Shimokawa H. Usefulness of fasudil, a Rho-kinase inhibitor, to treat intractable severe coronary spasm after coronary artery bypass surgery. J Cardiovasc Pharmacol. 2004 Sep;44(3):275-7. doi: 10.1097/01.fjc.0000134775.76636.3f.
- Kishi T, Hirooka Y, Masumoto A, Ito K, Kimura Y, Inokuchi K, Tagawa T, Shimokawa H, Takeshita A, Sunagawa K. Rho-kinase inhibitor improves increased vascular resistance and impaired vasodilation of the forearm in patients with heart failure. Circulation. 2005 May 31;111(21):2741-7. doi: 10.1161/CIRCULATIONAHA.104.510248.
- Witzenrath M, Ahrens B, Schmeck B, Kube SM, Hippenstiel S, Rosseau S, Hamelmann E, Suttorp N, Schutte H. Rho-kinase and contractile apparatus proteins in murine airway hyperresponsiveness. Exp Toxicol Pathol. 2008 Jun;60(1):9-15. doi: 10.1016/j.etp.2008.03.002. Epub 2008 Apr 22.
- Noma K, Rikitake Y, Oyama N, Yan G, Alcaide P, Liu PY, Wang H, Ahl D, Sawada N, Okamoto R, Hiroi Y, Shimizu K, Luscinskas FW, Sun J, Liao JK. ROCK1 mediates leukocyte recruitment and neointima formation following vascular injury. J Clin Invest. 2008 May;118(5):1632-44. doi: 10.1172/JCI29226.
- Lammermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Soldner R, Hirsch K, Keller M, Forster R, Critchley DR, Fassler R, Sixt M. Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature. 2008 May 1;453(7191):51-5. doi: 10.1038/nature06887.
- Smith A, Bracke M, Leitinger B, Porter JC, Hogg N. LFA-1-induced T cell migration on ICAM-1 involves regulation of MLCK-mediated attachment and ROCK-dependent detachment. J Cell Sci. 2003 Aug 1;116(Pt 15):3123-33. doi: 10.1242/jcs.00606. Epub 2003 Jun 10.
- van Buul JD, Hordijk PL. Signaling in leukocyte transendothelial migration. Arterioscler Thromb Vasc Biol. 2004 May;24(5):824-33. doi: 10.1161/01.ATV.0000122854.76267.5c. Epub 2004 Feb 19.
- Benais-Pont G, Punn A, Flores-Maldonado C, Eckert J, Raposo G, Fleming TP, Cereijido M, Balda MS, Matter K. Identification of a tight junction-associated guanine nucleotide exchange factor that activates Rho and regulates paracellular permeability. J Cell Biol. 2003 Mar 3;160(5):729-40. doi: 10.1083/jcb.200211047. Epub 2003 Feb 25.
- Li B, Zhao WD, Tan ZM, Fang WG, Zhu L, Chen YH. Involvement of Rho/ROCK signalling in small cell lung cancer migration through human brain microvascular endothelial cells. FEBS Lett. 2006 Jul 24;580(17):4252-60. doi: 10.1016/j.febslet.2006.06.056. Epub 2006 Jun 30.
- Nohria A, Grunert ME, Rikitake Y, Noma K, Prsic A, Ganz P, Liao JK, Creager MA. Rho kinase inhibition improves endothelial function in human subjects with coronary artery disease. Circ Res. 2006 Dec 8;99(12):1426-32. doi: 10.1161/01.RES.0000251668.39526.c7. Epub 2006 Nov 9.
- Bardi G, Niggli V, Loetscher P. Rho kinase is required for CCR7-mediated polarization and chemotaxis of T lymphocytes. FEBS Lett. 2003 May 8;542(1-3):79-83. doi: 10.1016/s0014-5793(03)00351-x.
- Lee JH, Katakai T, Hara T, Gonda H, Sugai M, Shimizu A. Roles of p-ERM and Rho-ROCK signaling in lymphocyte polarity and uropod formation. J Cell Biol. 2004 Oct 25;167(2):327-37. doi: 10.1083/jcb.200403091.
- Xue F, Takahara T, Yata Y, Xia Q, Nonome K, Shinno E, Kanayama M, Takahara S, Sugiyama T. Blockade of Rho/Rho-associated coiled coil-forming kinase signaling can prevent progression of hepatocellular carcinoma in matrix metalloproteinase-dependent manner. Hepatol Res. 2008 Aug;38(8):810-7. doi: 10.1111/j.1872-034X.2008.00333.x. Epub 2008 May 27.
- Wong CC, Wong CM, Ko FC, Chan LK, Ching YP, Yam JW, Ng IO. Deleted in liver cancer 1 (DLC1) negatively regulates Rho/ROCK/MLC pathway in hepatocellular carcinoma. PLoS One. 2008 Jul 23;3(7):e2779. doi: 10.1371/journal.pone.0002779.
- Ogawa T, Tashiro H, Miyata Y, Ushitora Y, Fudaba Y, Kobayashi T, Arihiro K, Okajima M, Asahara T. Rho-associated kinase inhibitor reduces tumor recurrence after liver transplantation in a rat hepatoma model. Am J Transplant. 2007 Feb;7(2):347-55. doi: 10.1111/j.1600-6143.2006.01647.x. Epub 2007 Jan 4.
- Wang DS, Dou KF, Li KZ, Song ZS. Enhancement of migration and invasion of hepatoma cells via a Rho GTPase signaling pathway. World J Gastroenterol. 2004 Jan 15;10(2):299-302. doi: 10.3748/wjg.v10.i2.299.
- Vishnubhotla R, Sun S, Huq J, Bulic M, Ramesh A, Guzman G, Cho M, Glover SC. ROCK-II mediates colon cancer invasion via regulation of MMP-2 and MMP-13 at the site of invadopodia as revealed by multiphoton imaging. Lab Invest. 2007 Nov;87(11):1149-58. doi: 10.1038/labinvest.3700674. Epub 2007 Sep 17.
- Kamai T, Tsujii T, Arai K, Takagi K, Asami H, Ito Y, Oshima H. Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Clin Cancer Res. 2003 Jul;9(7):2632-41.
- Sahai E, Marshall CJ. ROCK and Dia have opposing effects on adherens junctions downstream of Rho. Nat Cell Biol. 2002 Jun;4(6):408-15. doi: 10.1038/ncb796.
- Croft DR, Sahai E, Mavria G, Li S, Tsai J, Lee WM, Marshall CJ, Olson MF. Conditional ROCK activation in vivo induces tumor cell dissemination and angiogenesis. Cancer Res. 2004 Dec 15;64(24):8994-9001. doi: 10.1158/0008-5472.CAN-04-2052.
- Mizukami Y, Fujiki K, Duerr EM, Gala M, Jo WS, Zhang X, Chung DC. Hypoxic regulation of vascular endothelial growth factor through the induction of phosphatidylinositol 3-kinase/Rho/ROCK and c-Myc. J Biol Chem. 2006 May 19;281(20):13957-63. doi: 10.1074/jbc.M511763200. Epub 2006 Mar 16.
- Somlyo AV, Phelps C, Dipierro C, Eto M, Read P, Barrett M, Gibson JJ, Burnitz MC, Myers C, Somlyo AP. Rho kinase and matrix metalloproteinase inhibitors cooperate to inhibit angiogenesis and growth of human prostate cancer xenotransplants. FASEB J. 2003 Feb;17(2):223-34. doi: 10.1096/fj.02-0655com.
- Somlyo AV, Bradshaw D, Ramos S, Murphy C, Myers CE, Somlyo AP. Rho-kinase inhibitor retards migration and in vivo dissemination of human prostate cancer cells. Biochem Biophys Res Commun. 2000 Mar 24;269(3):652-9. doi: 10.1006/bbrc.2000.2343.
- Ying H, Biroc SL, Li WW, Alicke B, Xuan JA, Pagila R, Ohashi Y, Okada T, Kamata Y, Dinter H. The Rho kinase inhibitor fasudil inhibits tumor progression in human and rat tumor models. Mol Cancer Ther. 2006 Sep;5(9):2158-64. doi: 10.1158/1535-7163.MCT-05-0440.
- Bourguignon LY, Zhu H, Shao L, Zhu D, Chen YW. Rho-kinase (ROK) promotes CD44v(3,8-10)-ankyrin interaction and tumor cell migration in metastatic breast cancer cells. Cell Motil Cytoskeleton. 1999;43(4):269-87. doi: 10.1002/(SICI)1097-0169(1999)43:43.0.CO;2-5.
- Barreiro O, Yanez-Mo M, Serrador JM, Montoya MC, Vicente-Manzanares M, Tejedor R, Furthmayr H, Sanchez-Madrid F. Dynamic interaction of VCAM-1 and ICAM-1 with moesin and ezrin in a novel endothelial docking structure for adherent leukocytes. J Cell Biol. 2002 Jun 24;157(7):1233-45. doi: 10.1083/jcb.200112126. Epub 2002 Jun 24.
- Bivalacqua TJ, Champion HC, Usta MF, Cellek S, Chitaley K, Webb RC, Lewis RL, Mills TM, Hellstrom WJ, Kadowitz PJ. RhoA/Rho-kinase suppresses endothelial nitric oxide synthase in the penis: a mechanism for diabetes-associated erectile dysfunction. Proc Natl Acad Sci U S A. 2004 Jun 15;101(24):9121-6. doi: 10.1073/pnas.0400520101. Epub 2004 Jun 7.
- Ming XF, Viswambharan H, Barandier C, Ruffieux J, Kaibuchi K, Rusconi S, Yang Z. Rho GTPase/Rho kinase negatively regulates endothelial nitric oxide synthase phosphorylation through the inhibition of protein kinase B/Akt in human endothelial cells. Mol Cell Biol. 2002 Dec;22(24):8467-77. doi: 10.1128/MCB.22.24.8467-8477.2002.
- Tominaga T, Sugie K, Hirata M, Morii N, Fukata J, Uchida A, Imura H, Narumiya S. Inhibition of PMA-induced, LFA-1-dependent lymphocyte aggregation by ADP ribosylation of the small molecular weight GTP binding protein, rho. J Cell Biol. 1993 Mar;120(6):1529-37. doi: 10.1083/jcb.120.6.1529.
- Sanchez-Madrid F, del Pozo MA. Leukocyte polarization in cell migration and immune interactions. EMBO J. 1999 Feb 1;18(3):501-11. doi: 10.1093/emboj/18.3.501.
- Alevriadou BR. CAMs and Rho small GTPases: gatekeepers for leukocyte transendothelial migration. Focus on "VCAM-1-mediated Rac signaling controls endothelial cell-cell contacts and leukocyte transmigration". Am J Physiol Cell Physiol. 2003 Aug;285(2):C250-2. doi: 10.1152/ajpcell.00189.2003. No abstract available.
- Etienne S, Adamson P, Greenwood J, Strosberg AD, Cazaubon S, Couraud PO. ICAM-1 signaling pathways associated with Rho activation in microvascular brain endothelial cells. J Immunol. 1998 Nov 15;161(10):5755-61.
- Zhu F, Zhang Z, Wu G, Li Z, Zhang R, Ren J, Nong L. Rho kinase inhibitor fasudil suppresses migration and invasion though down-regulating the expression of VEGF in lung cancer cell line A549. Med Oncol. 2011 Jun;28(2):565-71. doi: 10.1007/s12032-010-9468-5. Epub 2010 Mar 19.
- Nakabayashi H, Shimizu K. HA1077, a Rho kinase inhibitor, suppresses glioma-induced angiogenesis by targeting the Rho-ROCK and the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signal pathways. Cancer Sci. 2011 Feb;102(2):393-9. doi: 10.1111/j.1349-7006.2010.01794.x. Epub 2010 Dec 19.
- Washida N, Wakino S, Tonozuka Y, Homma K, Tokuyama H, Hara Y, Hasegawa K, Minakuchi H, Fujimura K, Hosoya K, Hayashi K, Itoh H. Rho-kinase inhibition ameliorates peritoneal fibrosis and angiogenesis in a rat model of peritoneal sclerosis. Nephrol Dial Transplant. 2011 Sep;26(9):2770-9. doi: 10.1093/ndt/gfr012. Epub 2011 Mar 4.
- Kuno M, Takai S, Matsushima-Nishiwaki R, Minamitani C, Mizutani J, Otsuka T, Harada A, Adachi S, Kozawa O, Tokuda H. Rho-kinase inhibitors decrease TGF-beta-stimulated VEGF synthesis through stress-activated protein kinase/c-Jun N-terminal kinase in osteoblasts. Biochem Pharmacol. 2009 Jan 15;77(2):196-203. doi: 10.1016/j.bcp.2008.10.014. Epub 2008 Oct 19.
- Takata K, Morishige K, Takahashi T, Hashimoto K, Tsutsumi S, Yin L, Ohta T, Kawagoe J, Takahashi K, Kurachi H. Fasudil-induced hypoxia-inducible factor-1alpha degradation disrupts a hypoxia-driven vascular endothelial growth factor autocrine mechanism in endothelial cells. Mol Cancer Ther. 2008 Jun;7(6):1551-61. doi: 10.1158/1535-7163.MCT-07-0428.
- Hata Y, Miura M, Nakao S, Kawahara S, Kita T, Ishibashi T. Antiangiogenic properties of fasudil, a potent Rho-Kinase inhibitor. Jpn J Ophthalmol. 2008 Jan-Feb;52(1):16-23. doi: 10.1007/s10384-007-0487-5. Epub 2008 Mar 28.
- Liu C, Li Y, Yu J, Feng L, Hou S, Liu Y, Guo M, Xie Y, Meng J, Zhang H, Xiao B, Ma C. Targeting the shift from M1 to M2 macrophages in experimental autoimmune encephalomyelitis mice treated with fasudil. PLoS One. 2013;8(2):e54841. doi: 10.1371/journal.pone.0054841. Epub 2013 Feb 13.
- Ozeki K, Tanida S, Morimoto C, Inoue Y, Mizoshita T, Tsukamoto H, Shimura T, Kataoka H, Kamiya T, Nishiwaki E, Ishiguro H, Higashiyama S, Joh T. Telmisartan inhibits cell proliferation by blocking nuclear translocation of ProHB-EGF C-terminal fragment in colon cancer cells. PLoS One. 2013;8(2):e56770. doi: 10.1371/journal.pone.0056770. Epub 2013 Feb 22.
- Sharpe M, Jarvis B, Goa KL. Telmisartan: a review of its use in hypertension. Drugs. 2001;61(10):1501-29. doi: 10.2165/00003495-200161100-00009.
- Smith DH, Matzek KM, Kempthorne-Rawson J. Dose response and safety of telmisartan in patients with mild to moderate hypertension. J Clin Pharmacol. 2000 Dec;40(12 Pt 1):1380-90.
- Stangier J, Su CA, Roth W. Pharmacokinetics of orally and intravenously administered telmisartan in healthy young and elderly volunteers and in hypertensive patients. J Int Med Res. 2000 Jul-Aug;28(4):149-67. doi: 10.1177/147323000002800401.
- Forclaz A, Maillard M, Nussberger J, Brunner HR, Burnier M. Angiotensin II receptor blockade: is there truly a benefit of adding an ACE inhibitor? Hypertension. 2003 Jan;41(1):31-6. doi: 10.1161/01.hyp.0000047512.58862.a9.
- Levine JE, Paczesny S, Sarantopoulos S. Clinical applications for biomarkers of acute and chronic graft-versus-host disease. Biol Blood Marrow Transplant. 2012 Jan;18(1 Suppl):S116-24. doi: 10.1016/j.bbmt.2011.10.019.
- Paczesny S. Discovery and validation of graft-versus-host disease biomarkers. Blood. 2013 Jan 24;121(4):585-94. doi: 10.1182/blood-2012-08-355990. Epub 2012 Nov 19.
- Levine JE, Logan BR, Wu J, Alousi AM, Bolanos-Meade J, Ferrara JL, Ho VT, Weisdorf DJ, Paczesny S. Acute graft-versus-host disease biomarkers measured during therapy can predict treatment outcomes: a Blood and Marrow Transplant Clinical Trials Network study. Blood. 2012 Apr 19;119(16):3854-60. doi: 10.1182/blood-2012-01-403063. Epub 2012 Mar 1.
- Mueller T, Dieplinger B. The Presage((R)) ST2 Assay: analytical considerations and clinical applications for a high-sensitivity assay for measurement of soluble ST2. Expert Rev Mol Diagn. 2013 Jan;13(1):13-30. doi: 10.1586/erm.12.128.
- Ferrara JL, Harris AC, Greenson JK, Braun TM, Holler E, Teshima T, Levine JE, Choi SW, Huber E, Landfried K, Akashi K, Vander Lugt M, Reddy P, Chin A, Zhang Q, Hanash S, Paczesny S. Regenerating islet-derived 3-alpha is a biomarker of gastrointestinal graft-versus-host disease. Blood. 2011 Dec 15;118(25):6702-8. doi: 10.1182/blood-2011-08-375006. Epub 2011 Oct 6.
- Holler E, Landfried K, Meier J, Hausmann M, Rogler G. The role of bacteria and pattern recognition receptors in GVHD. Int J Inflam. 2010 Oct 31;2010:814326. doi: 10.4061/2010/814326.
- Penack O, Holler E, van den Brink MR. Graft-versus-host disease: regulation by microbe-associated molecules and innate immune receptors. Blood. 2010 Mar 11;115(10):1865-72. doi: 10.1182/blood-2009-09-242784. Epub 2009 Dec 30.
- Cooke KR, Gerbitz A, Crawford JM, Teshima T, Hill GR, Tesolin A, Rossignol DP, Ferrara JL. LPS antagonism reduces graft-versus-host disease and preserves graft-versus-leukemia activity after experimental bone marrow transplantation. J Clin Invest. 2001 Jun;107(12):1581-9. doi: 10.1172/JCI12156.
- Lv M, Ye HG, Zhao XS, Zhao XY, Chang YJ, Liu DH, Xu LP, Huang XJ. Ceruloplasmin is a potential biomarker for aGvHD following allogeneic hematopoietic stem cell transplantation. PLoS One. 2013;8(3):e58735. doi: 10.1371/journal.pone.0058735. Epub 2013 Mar 7.
- Romaschin AD, Klein DJ, Marshall JC. Bench-to-bedside review: Clinical experience with the endotoxin activity assay. Crit Care. 2012 Dec 3;16(6):248. doi: 10.1186/cc11495.
- Hilmi I, Kellum J, Planinsic R, Foster D, Abdullah A, Damian D, Gligor S, Klein D, Abu-elmagd K. Endotoxemia is common following abdominal organ transplantation and is associated with reperfusion and rejection.Journal of Organ Dysfunction. Dec 2009, Vol. 5 Issue 4, p254-260.
- Sanada Y, Mizuta K, Urahashi T, Ihara Y, Wakiya T, Okada N, Yamada N, Ushijima K, Otomo S, Sakamoto K, Yasuda Y, Kawarasaki H. Impact of endotoxin measured by an endotoxin activity assay during liver transplantation. J Surg Res. 2013 Apr;180(2):349-55. doi: 10.1016/j.jss.2012.05.004. Epub 2012 May 24.
- Ikeda T, Ikeda K, Suda S, Ueno T. Usefulness of the endotoxin activity assay as a biomarker to assess the severity of endotoxemia in critically ill patients. Innate Immun. 2014 Nov;20(8):881-7. doi: 10.1177/1753425913516885. Epub 2014 Jan 7.
- Jenq RR, Ubeda C, Taur Y, Menezes CC, Khanin R, Dudakov JA, Liu C, West ML, Singer NV, Equinda MJ, Gobourne A, Lipuma L, Young LF, Smith OM, Ghosh A, Hanash AM, Goldberg JD, Aoyama K, Blazar BR, Pamer EG, van den Brink MR. Regulation of intestinal inflammation by microbiota following allogeneic bone marrow transplantation. J Exp Med. 2012 May 7;209(5):903-11. doi: 10.1084/jem.20112408. Epub 2012 Apr 30.
- Arck P, Handjiski B, Hagen E, Pincus M, Bruenahl C, Bienenstock J, Paus R. Is there a 'gut-brain-skin axis'? Exp Dermatol. 2010 May;19(5):401-5. doi: 10.1111/j.1600-0625.2009.01060.x. Epub 2010 Jan 25.
- Gomez A, Hammer S, Braun T, Hanash S, Ferrara J, Greenson J, Wang H, Zhang Q, Vander Lugt M, Pongtornpipat P, Lamiman K, Colon M, Chang L, Choi S, Levine J, Harris A, Couriel D, Reddy P, Paczesny S. A novel CD4+CD146+CCR5+ T-cell population is a biomarker of intestinal graft-versus-host disease. 39th meeting of the European Group for Blood and Marrow Transplantation Wednesday, April 10, 2013, 09:30 - 09:42
- Cheng CI, Lin YC, Tsai TH, Lin HS, Liou CW, Chang WN, Lu CH, Yuen CM, Yip HK. The prognostic values of leukocyte Rho kinase activity in acute ischemic stroke. Biomed Res Int. 2014;2014:214587. doi: 10.1155/2014/214587. Epub 2014 Feb 27.
- Patel PA, Patravale VB, Commercial Telmisartan Tablets: A Comparative Evaluation with Innovator Brand Micardis, International Journal of Pharma Sciences and Research (IJPSR) 2010, 1(8): 282-292.
- Michel MC, Bohner H, Koster J, Schafers R, Heemann U. Safety of telmisartan in patients with arterial hypertension : an open-label observational study. Drug Saf. 2004;27(5):335-44. doi: 10.2165/00002018-200427050-00005.
- Schumacher H, Mancia G. The safety profile of telmisartan as monotherapy or combined with hydrochlorothiazide: a retrospective analysis of 50 studies. Blood Press Suppl. 2008 Jun;1:32-40. doi: 10.1080/08038020802144383.
- Bahr IN, Tretter P, Kruger J, Stark RG, Schimkus J, Unger T, Kappert K, Scholze J, Parhofer KG, Kintscher U. High-dose treatment with telmisartan induces monocytic peroxisome proliferator-activated receptor-gamma target genes in patients with the metabolic syndrome. Hypertension. 2011 Oct;58(4):725-32. doi: 10.1161/HYPERTENSIONAHA.111.173542. Epub 2011 Aug 29.
- Chetty VT, Damjanovic S, Gerstein H, Singh N, Yusuf S, Anand SS, Sharma AM. Metabolic effects of telmisartan in subjects with abdominal obesity: a prospective randomized controlled trial. Blood Press. 2014 Feb;23(1):54-60. doi: 10.3109/08037051.2013.791411. Epub 2013 Jun 3.
- White WB. Comparative effects of telmisartan in the treatment of hypertension. J Clin Hypertens (Greenwich). 2002 Jul-Aug;4(4 Suppl 1):20-5. doi: 10.1111/j.1524-6175.2002.01585.x.
- Eriguchi Y, Takashima S, Oka H, Shimoji S, Nakamura K, Uryu H, Shimoda S, Iwasaki H, Shimono N, Ayabe T, Akashi K, Teshima T. Graft-versus-host disease disrupts intestinal microbial ecology by inhibiting Paneth cell production of alpha-defensins. Blood. 2012 Jul 5;120(1):223-31. doi: 10.1182/blood-2011-12-401166. Epub 2012 Apr 24.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查,以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2015年7月7日
初级完成 (实际的)
2023年1月5日
研究完成 (实际的)
2023年1月5日
研究注册日期
首次提交
2015年1月5日
首先提交符合 QC 标准的
2015年1月9日
首次发布 (估计的)
2015年1月14日
研究记录更新
最后更新发布 (实际的)
2026年4月2日
上次提交的符合 QC 标准的更新
2026年3月20日
最后验证
2026年3月1日
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.