氨基酸亮氨酸治疗输血依赖性 Diamond Blackfan 贫血患者的 I/II 期试验性研究 (LeucineDBA)
2022年11月18日 更新者：Adrianna Vlachos, MD、Northwell Health
以骨髓衰竭为模型，使用新疗法重建血细胞生产和促进器官性能：氨基酸亮氨酸治疗输血依赖性钻石黑范贫血患者的 I/II 期试验性研究
这项研究将确定在依赖红细胞输血的 Diamond Blackfan 贫血 (DBA) 患者中给予氨基酸、亮氨酸的安全性和可能性。
亮氨酸有望在 DBA 患者中产生反应，达到红细胞生成增加的程度。 然后可以减少红细胞输注的频率或可能停止输注。
研究人员将研究给予 DBA 患者亮氨酸的副作用（如果有的话）。 将在基线和研究期间获得亮氨酸的亮氨酸水平。
药物亮氨酸将以胶囊形式提供，每天服用 3 次，共服用 9 个月。
研究概览
详细说明
亮氨酸将以胶囊的形式提供给参与者，每天服用 3 次。
血液中的血红蛋白水平将每 3-4 周监测一次，持续 9 个月。
整个研究将持续 12-15 个月。
受试者必须年满两岁，并且在入组前接受输血超过六个月。
研究类型
介入性
注册 (实际的)
55
阶段
- 阶段2
- 阶段1
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
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Arizona
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Phoenix、Arizona、美国、85016
- Phoenix Children's Hospital
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California
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Palo Alto、California、美国、94304
- Stanford University Medical Center
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Indiana
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Indianapolis、Indiana、美国、46202
- Riley Hospital for Children
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Kentucky
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Louisville、Kentucky、美国、40202
- University of Louisville
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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
- University of Michigan C.S. Mott Children's Hospital
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Missouri
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Columbia、Missouri、美国、65201
- University of Missouri-Columbia Women's and Children's Hospital
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Nevada
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Las Vegas、Nevada、美国、89109
- Children's Specialty Center of Nevada
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New York
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New Hyde Park、New York、美国、11040
- Cohen Children's Medical Center of New York
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Pennsylvania
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Philadelphia、Pennsylvania、美国、19104
- Children's Hospital of Philadelphia
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Texas
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Dallas、Texas、美国、75390
- UT Southwestern Medical Center
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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
1年 及以上 (孩子、成人、年长者)
接受健康志愿者
不
有资格学习的性别
全部
描述
纳入标准：
- 被诊断出患有 Diamond Blackfan 贫血症，发表在英国血液学杂志上
- 输血依赖
- 2岁及以上
- 足够的肾功能
- 足够的肝功能
- 如果患者是经期女性且有足够避孕措施的文件，则 B-HCG 呈阴性
- 签署知情同意书
排除标准：
- 已知对支链氨基酸过敏
- 先天性氨基酸代谢紊乱的诊断
- 既往造血干细胞移植
- 怀孕或计划在试验期间怀孕
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 |
|---|---|
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其他：亮氨酸
没有替代治疗臂
|
亮氨酸的剂量将取决于体表面积 (BSA)： 每天 3 次口服亮氨酸 700 mg/m2/剂量
其他名称：
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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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依赖输血的 Diamond Blackfan 贫血患者对亮氨酸的反应
大体时间：9个月
|
主要结果是 9 个月时观察到的反应类型。 对治疗的反应可以是以下之一：
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9个月
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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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亮氨酸引起的严重不良事件
大体时间：9个月
|
参与者服用亮氨酸时发生的不良事件
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9个月
|
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：Adrianna Vlachos, MD、Feinstein Institutes for Medical Research; Cohen Children's Medical Center
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
- Abkowitz JL, Schaison G, Boulad F, Brown DL, Buchanan GR, Johnson CA, Murray JC, Sabo KM. Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis. Blood. 2002 Oct 15;100(8):2687-91. doi: 10.1182/blood.V100.8.2687.
- Bastion Y, Bordigoni P, Debre M, Girault D, Leblanc T, Tchernia G, Ball S, McGuckin C, Gordon-Smith EC, Bekassy A, et al. Sustained response after recombinant interleukin-3 in diamond blackfan anemia. Blood. 1994 Jan 15;83(2):617-8. No abstract available.
- Cmejla R, Cmejlova J, Handrkova H, Petrak J, Pospisilova D. Ribosomal protein S17 gene (RPS17) is mutated in Diamond-Blackfan anemia. Hum Mutat. 2007 Dec;28(12):1178-82. doi: 10.1002/humu.20608.
- Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet. 1999 Feb;21(2):169-75. doi: 10.1038/5951.
- Farrar JE, Nater M, Caywood E, McDevitt MA, Kowalski J, Takemoto CM, Talbot CC Jr, Meltzer P, Esposito D, Beggs AH, Schneider HE, Grabowska A, Ball SE, Niewiadomska E, Sieff CA, Vlachos A, Atsidaftos E, Ellis SR, Lipton JM, Gazda HT, Arceci RJ. Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond-Blackfan anemia. Blood. 2008 Sep 1;112(5):1582-92. doi: 10.1182/blood-2008-02-140012. Epub 2008 Jun 5.
- Gazda HT, Grabowska A, Merida-Long LB, Latawiec E, Schneider HE, Lipton JM, Vlachos A, Atsidaftos E, Ball SE, Orfali KA, Niewiadomska E, Da Costa L, Tchernia G, Niemeyer C, Meerpohl JJ, Stahl J, Schratt G, Glader B, Backer K, Wong C, Nathan DG, Beggs AH, Sieff CA. Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. Am J Hum Genet. 2006 Dec;79(6):1110-8. doi: 10.1086/510020. Epub 2006 Nov 2.
- Gazda HT, Sheen MR, Vlachos A, Choesmel V, O'Donohue MF, Schneider H, Darras N, Hasman C, Sieff CA, Newburger PE, Ball SE, Niewiadomska E, Matysiak M, Zaucha JM, Glader B, Niemeyer C, Meerpohl JJ, Atsidaftos E, Lipton JM, Gleizes PE, Beggs AH. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet. 2008 Dec;83(6):769-80. doi: 10.1016/j.ajhg.2008.11.004.
- Leblanc TM, Da Costa L, Marie I, Demolis P, Tchernia G. Metoclopramide treatment in DBA patients: no complete response in a French prospective study. Blood. 2007 Mar 1;109(5):2266-7. doi: 10.1182/blood-2006-08-039545. No abstract available.
- Lipton JM, Atsidaftos E, Zyskind I, Vlachos A. Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: an update from the Diamond Blackfan Anemia Registry. Pediatr Blood Cancer. 2006 May 1;46(5):558-64. doi: 10.1002/pbc.20642.
- Vlachos A, Ball S, Dahl N, Alter BP, Sheth S, Ramenghi U, Meerpohl J, Karlsson S, Liu JM, Leblanc T, Paley C, Kang EM, Leder EJ, Atsidaftos E, Shimamura A, Bessler M, Glader B, Lipton JM; Participants of Sixth Annual Daniella Maria Arturi International Consensus Conference. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. Br J Haematol. 2008 Sep;142(6):859-76. doi: 10.1111/j.1365-2141.2008.07269.x. Epub 2008 Jul 30.
- Vlachos A, Federman N, Reyes-Haley C, Abramson J, Lipton JM. Hematopoietic stem cell transplantation for Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Bone Marrow Transplant. 2001 Feb;27(4):381-6. doi: 10.1038/sj.bmt.1702784.
- Vlachos A, Klein GW, Lipton JM. The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia. J Pediatr Hematol Oncol. 2001 Aug-Sep;23(6):377-82. doi: 10.1097/00043426-200108000-00015.
- Ozsoylu S. Oral megadose methylprednisolone for Diamond-Blackfan anemia. Blood. 1994 Nov 1;84(9):3245-7. No abstract available.
- Bernini JC, Carrillo JM, Buchanan GR. High-dose intravenous methylprednisolone therapy for patients with Diamond-Blackfan anemia refractory to conventional doses of prednisone. J Pediatr. 1995 Oct;127(4):654-9. doi: 10.1016/s0022-3476(95)70134-6.
- Buchanan GR; International Diamond-Blackfan Anemia Study Group. Oral megadose methylprednisolone therapy for refractory Diamond-Blackfan anemia. International Diamond-Blackfan Anemia Study Group. J Pediatr Hematol Oncol. 2001 Aug-Sep;23(6):353-6. doi: 10.1097/00043426-200108000-00006.
- Totterman TH, Nisell J, Killander A, Gahrton G, Lonnqvist B. Successful treatment of pure red-cell aplasia with cyclosporin. Lancet. 1984 Sep 22;2(8404):693. doi: 10.1016/s0140-6736(84)91245-5. No abstract available.
- Williams DL, Mageed AS, Findley H, Ragab AH. Cyclosporine in the treatment of red cell aplasia. Am J Pediatr Hematol Oncol. 1987 Winter;9(4):314-6. doi: 10.1097/00043426-198724000-00007.
- Seip M, Zanussi GF. Cyclosporine in steroid-resistant Diamond-Blackfan anaemia. Acta Paediatr Scand. 1988 May;77(3):464-6. doi: 10.1111/j.1651-2227.1988.tb10682.x.
- Leonard EM, Raefsky E, Griffith P, Kimball J, Nienhuis AW, Young NS. Cyclosporine therapy of aplastic anaemia, congenital and acquired red cell aplasia. Br J Haematol. 1989 Jun;72(2):278-84. doi: 10.1111/j.1365-2141.1989.tb07695.x.
- Splain J, Berman BW. Cyclosporin A treatment for Diamond-Blackfan anemia. Am J Hematol. 1992 Mar;39(3):208-11. doi: 10.1002/ajh.2830390310.
- Monteserin MC, Garcia Vela JA, Ona F, Lastra AM. Cyclosporin A for Diamond-Blackfan anemia: a new case. Am J Hematol. 1993 Apr;42(4):406-7. doi: 10.1002/ajh.2830420419. No abstract available.
- Alessandri AJ, Rogers PC, Wadsworth LD, Davis JH. Diamond-blackfan anemia and cyclosporine therapy revisited. J Pediatr Hematol Oncol. 2000 Mar-Apr;22(2):176-9. doi: 10.1097/00043426-200003000-00020.
- Bobey NA, Carcao M, Dror Y, Freedman MH, Dahl N, Woodman RC. Sustained cyclosporine-induced erythropoietic response in identical male twins with diamond-blackfan anemia. J Pediatr Hematol Oncol. 2003 Nov;25(11):914-8. doi: 10.1097/00043426-200311000-00018.
- Harris SI, Weinberg JB. Treatment of red cell aplasia with antithymocyte globulin: repeated inductions of complete remissions in two patients. Am J Hematol. 1985 Oct;20(2):183-6. doi: 10.1002/ajh.2830200212.
- Roychowdhury DF, Linker CA. Pure red cell aplasia complicating an ABO-compatible allogeneic bone marrow transplantation, treated successfully with antithymocyte globulin. Bone Marrow Transplant. 1995 Sep;16(3):471-2.
- Abkowitz JL, Powell JS, Nakamura JM, Kadin ME, Adamson JW. Pure red cell aplasia: response to therapy with anti-thymocyte globulin. Am J Hematol. 1986 Dec;23(4):363-71. doi: 10.1002/ajh.2830230408.
- McGuire WA, Yang HH, Bruno E, Brandt J, Briddell R, Coates TD, Hoffman R. Treatment of antibody-mediated pure red-cell aplasia with high-dose intravenous gamma globulin. N Engl J Med. 1987 Oct 15;317(16):1004-8. doi: 10.1056/NEJM198710153171606. No abstract available.
- Bejaoui M, Fitouri Z, Sfar MT, Lakhoua R. Failure of immunosuppressive therapy and high-dose intravenous immunoglobulins in four transfusion-dependent, steroid-unresponsive Blackfan-Diamond anemia patients. Haematologica. 1993 Jan-Feb;78(1):38-9.
- Sumimoto S, Kawai M, Kasajima Y, Hamamoto T. Intravenous gamma-globulin therapy in Diamond-Blackfan anemia. Acta Paediatr Jpn. 1992 Apr;34(2):179-80. doi: 10.1111/j.1442-200x.1992.tb00947.x.
- Miceli Sopo S, Pesaresi MA, Pastore M, Stabile A. Intravenous immunoglobulin in Diamond-Blackfan anaemia. Eur J Pediatr. 1990 Aug;149(11):779-80. doi: 10.1007/BF01957279.
- Halperin DS, Estrov Z, Freedman MH. Diamond-Blackfan anemia: promotion of marrow erythropoiesis in vitro by recombinant interleukin-3. Blood. 1989 Apr;73(5):1168-74.
- Dunbar CE, Smith DA, Kimball J, Garrison L, Nienhuis AW, Young NS. Treatment of Diamond-Blackfan anaemia with haematopoietic growth factors, granulocyte-macrophage colony stimulating factor and interleukin 3: sustained remissions following IL-3. Br J Haematol. 1991 Oct;79(2):316-21. doi: 10.1111/j.1365-2141.1991.tb04540.x.
- Gillio AP, Faulkner LB, Alter BP, Reilly L, Klafter R, Heller G, Young DC, Lipton JM, Moore MA, O'Reilly RJ. Treatment of Diamond-Blackfan anemia with recombinant human interleukin-3. Blood. 1993 Aug 1;82(3):744-51.
- Gillio AP, Faulkner LB, Alter BP, Reilly L, Klafter R, Heller G, Young DC, Lipton JM, Moore MA, O'Reilly RJ. Successful treatment of Diamond-Blackfan anemia with interleukin 3. Stem Cells. 1993 Jul;11 Suppl 2:123-30. doi: 10.1002/stem.5530110820.
- Olivieri NF, Feig SA, Valentino L, Berriman AM, Shore R, Freedman MH. Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia. Blood. 1994 May 1;83(9):2444-50.
- Ball SE, Tchernia G, Wranne L, Bastion Y, Bekassy NA, Bordigoni P, Debre M, Elinder G, Kamps WA, Lanning M, et al. Is there a role for interleukin-3 in Diamond-Blackfan anaemia? Results of a European multicentre study. Br J Haematol. 1995 Oct;91(2):313-8. doi: 10.1111/j.1365-2141.1995.tb05295.x.
- Akiyama M, Yanagisawa T, Yuza Y, Yokoi K, Ariga M, Fujisawa K, Hoshi Y, Eto Y. Successful treatment of Diamond-Blackfan anemia with metoclopramide. Am J Hematol. 2005 Apr;78(4):295-8. doi: 10.1002/ajh.20278.
- Cynober L, Harris RA. Symposium on branched-chain amino acids: conference summary. J Nutr. 2006 Jan;136(1 Suppl):333S-6S. doi: 10.1093/jn/136.1.333S. No abstract available.
- Choudry HA, Pan M, Karinch AM, Souba WW. Branched-chain amino acid-enriched nutritional support in surgical and cancer patients. J Nutr. 2006 Jan;136(1 Suppl):314S-8S. doi: 10.1093/jn/136.1.314S.
- Pospisilova D, Cmejlova J, Hak J, Adam T, Cmejla R. Successful treatment of a Diamond-Blackfan anemia patient with amino acid leucine. Haematologica. 2007 May;92(5):e66-7. doi: 10.3324/haematol.11498. No abstract available.
- Kimball SR, Jefferson LS. Signaling pathways and molecular mechanisms through which branched-chain amino acids mediate translational control of protein synthesis. J Nutr. 2006 Jan;136(1 Suppl):227S-31S. doi: 10.1093/jn/136.1.227S.
- Pencharz PB, Ball RO. Amino acid needs for early growth and development. J Nutr. 2004 Jun;134(6 Suppl):1566S-1568S. doi: 10.1093/jn/134.6.1566S.
- Bernardini P, Fischer JE. Amino acid imbalance and hepatic encephalopathy. Annu Rev Nutr. 1982;2:419-54. doi: 10.1146/annurev.nu.02.070182.002223. No abstract available.
- Poon RT, Yu WC, Fan ST, Wong J. Long-term oral branched chain amino acids in patients undergoing chemoembolization for hepatocellular carcinoma: a randomized trial. Aliment Pharmacol Ther. 2004 Apr 1;19(7):779-88. doi: 10.1111/j.1365-2036.2004.01920.x.
- Plaitakis A, Smith J, Mandeli J, Yahr MD. Pilot trial of branched-chain aminoacids in amyotrophic lateral sclerosis. Lancet. 1988 May 7;1(8593):1015-8. doi: 10.1016/s0140-6736(88)91841-7.
- Pass KA, Lane PA, Fernhoff PM, Hinton CF, Panny SR, Parks JS, Pelias MZ, Rhead WJ, Ross SI, Wethers DL, Elsas LJ 2nd. US newborn screening system guidelines II: follow-up of children, diagnosis, management, and evaluation. Statement of the Council of Regional Networks for Genetic Services (CORN). J Pediatr. 2000 Oct;137(4 Suppl):S1-46. doi: 10.1067/mpd.2000.109437. No abstract available.
- Cmejlova J, Dolezalova L, Pospisilova D, Petrtylova K, Petrak J, Cmejla R. Translational efficiency in patients with Diamond-Blackfan anemia. Haematologica. 2006 Nov;91(11):1456-64.
- Hutson SM, Sweatt AJ, Lanoue KF. Branched-chain [corrected] amino acid metabolism: implications for establishing safe intakes. J Nutr. 2005 Jun;135(6 Suppl):1557S-64S. doi: 10.1093/jn/135.6.1557S. Erratum In: J Nutr. 2005 Aug;135(8):2009.
- Lab Advisor(TM); Leucine Measurements in Micromedex (R) Healthcare Series. 2010Thomson Reuters
- Jellin JM, Gregory P, Batz F. Pharmacist's letter/ Prescriber's Letter Natural Medicines Comprehensive Database, 3rd ed, Therapeutic Research Faculty, Stockton, CA, 2000.
- Braverman ER. The Healing Nutrients Within. New Canaan, CT: Keats Publishing, Inc. 1997; 339
- Gilman AG, Rall JW, Nies AD et al (eds): Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed. Pergamon Press, New York, NY, 1990.
- AMA Department of Drugs; AMA Drug Evaluations, 6th ed. American Medical Association, Chicago, IL,1986.
- Tietz NE (Ed); Clinical Guide to Laboratory Tests, 3rd ed W. B. Saunders, Philadelphia, PA, 1995.
- Henry JB: Clinical Diagnosis and Management by Laboratory Methods, 20th ed. Saunders 2001.
- Sax HC, Talamini MA, Fischer JE. Clinical use of branched-chain amino acids in liver disease, sepsis, trauma, and burns. Arch Surg. 1986 Mar;121(3):358-66. doi: 10.1001/archsurg.1986.01400030120019.
- Vlachos A, Atsidaftos E, Lababidi ML, Muir E, Rogers ZR, Alhushki W, Bernstein J, Glader B, Gruner B, Hartung H, Knoll C, Loew T, Nalepa G, Narla A, Panigrahi AR, Sieff CA, Walkovich K, Farrar JE, Lipton JM. L-leucine improves anemia and growth in patients with transfusion-dependent Diamond-Blackfan anemia: Results from a multicenter pilot phase I/II study from the Diamond-Blackfan Anemia Registry. Pediatr Blood Cancer. 2020 Dec;67(12):e28748. doi: 10.1002/pbc.28748. Epub 2020 Oct 6.
有用的网址
- Diamond Blackfan Anemia Registry - a registry for patients with DBA in North America
- Daniella Maria Arturi Foundation is a family sponsored group which facilitates research for DBA.
- The DBA foundation is a family sponsored organization who raise funds for research and provides emotional support to families.
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)
2013年6月1日
初级完成 (实际的)
2018年6月30日
研究完成 (实际的)
2020年11月30日
研究注册日期
首次提交
2011年5月20日
首先提交符合 QC 标准的
2011年5月26日
首次发布 (估计)
2011年5月30日
研究记录更新
最后更新发布 (实际的)
2022年12月2日
上次提交的符合 QC 标准的更新
2022年11月18日
最后验证
2022年11月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- 12-375B
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
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.