Longitudinal CMV

纵向CMV

• 批准号: 10001430
• 负责人: DAVID W KIMBERLIN
• 金额: $ 37.56万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10001430
• 关键词: 12 year old; 2 year old; Adolescent; Age; Alabama; Animal Model; Antiviral Agents; Antiviral Therapy; Back; Birth; Child; Clinical Research; Clinical Treatment; Development; Developmental Delay Disorders; Disease; Enrollment; Follow-Up Studies; Funding; Future; Ganciclovir; Hearing; Infant; Institution; Intelligence; Knowledge; Life; Longitudinal Studies; Longterm Follow-up; Malignant Neoplasms; Medical History; Mental Retardation; Oral; Outcome; Patients; Perinatal Infection; Population; Prodrugs; Puberty; Publishing; Randomized; Rare Diseases; Safety; Sensorineural Hearing Loss; Site; Study Subject; Teratogens; Testing; Time; Toxic effect; United States National Institutes of Health; Universities; Valganciclovir; Viral; anti-viral efficacy; cancer diagnosis; carcinogenicity; cohort; congenital cytomegalovirus; congenital infection; design; experience; follow-up; improved; infancy; neonate; neurodevelopment; non-genetic; prospective; recruit; symptom treatment; treatment duration; treatment effect

This project, A Longitudinal Study of the Durability of Valganciclovir Therapy on Long-Term Hearing and Neurodevelopmental Outcomes in Adolescents Treated During Infancy for Symptomatic Congenital Cytomegalovirus (CMV) Diseases, will be led by David W. Kimberlin, MD. It uses a randomized cohort from an earlier study of the treatment of infants with symptomatic congenital CMV disease to ascertain whether the treatment benefits on hearing and developmental outcomes seen to 2 years of age persist over the ensuing decade. That study, known as the CASG 112 trial, was conducted by the Collaborative Antiviral Study Group and enrolled 109 subjects between 2008 and 2011. It documented that a 6 month duration of treatment of symptomatic congenital CMV provided superior hearing and developmental outcomes compared with 6 weeks of antiviral treatment, and that these benefits persisted to 2 years of age. What is not known, though, is whether these benefits persist longer than this, and whether there are any longer-term toxicities from valganciclovir therapy provided very early in life. Subjects previously enrolled in the CASG 112 study are approaching their 12th birthday. We will bring them back when they are 12 years of age for hearing and developmental assessments. Returning subjects also will have a pubertal assessment as a marker for potential gonadotoxicity from the earlier valganciclovir therapy, and for inquiry about development of any cancers. The results of this study will be important. If these benefits on hearing and development are durable, it suggests that treatment does not need to be longer than 6 months duration. On the other hand, if the benefits of 6 months of treatment are not durable (that is, if they wane over time), this is of equal value because it illumines the next study that needs to be conducted to assesses treatment of perhaps 12 months (or even longer), with or without the addition of a second antiviral drug such as letermovir. Also, if longer-term toxicities from the earlier valganciclovir therapy are identified, this will have a direct impact on the clinical treatment of patients with symptomatic congenital CMV disease. Most importantly, knowledge will be gained from this longitudinal study of long-term hearing and developmental outcomes following what is now the standard duration of treatment (6 months) that will benefit children who have received this course of therapy.

该项目是一项纵向研究，对长期听力和长期听力和 婴儿期治疗的青少年的神经发育结果 巨细胞病毒（CMV）疾病将由医学博士David W. Kimberlin领导。它使用来自 早期研究对症状先天性CMV疾病的婴儿的治疗 在随后的情况下，听力和发展成果的治疗益处持续了 十年。该研究称为CASG 112试验，由协作抗病毒研究组进行 并在2008年至2011年期间招募了109名受试者。它记录了6个月的治疗时间 有症状的先天性CMV提供了出色的听力和发育结果，而6周 抗病毒治疗，这些好处持续到2岁。但是，尚不清楚的是 这些好处是否持续比这更长，以及是否存在任何长期的毒性 Valganciclovir疗法在生命的早期提供。 先前参加CASG 112研究的受试者即将接近他们的12岁生日。我们将带他们 回到他们12岁的听力和发育评估时。返回的主题也将 有一个青春期的评估，作为早期Valganciclovir疗法潜在性腺毒性的标记， 并查询任何癌症的发展。 这项研究的结果将很重要。如果听力和发展中的这些好处是耐用的，则 表明治疗不需要持续时间超过6个月。另一方面，如果有益 6个月的治疗不耐用（也就是说，如果它们随着时间的流逝而减弱），这是同等价值的 照明下一项需要进行的下一项研究，以评估约12个月的治疗方法（甚至 更长的时间），或不添加第二种抗病毒药物（例如letermovir）。另外，如果长期毒性 从较早的Valganciclovir疗法中，这将直接影响 有症状的先天性CMV疾病患者。最重要的是，从中获得知识 长期听力和发展结果的纵向研究如今已成为标准 治疗持续时间（6个月）将使接受此治疗过程的儿童受益。