Longitudinal CMV

纵向CMV

基本信息

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
项目类别：
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

项目摘要

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“缬更昔洛韦治疗对长期听力和听力的持久性的纵向研究” 婴儿期接受症状性先天性神经发育障碍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。它使用来自一个随机队列对患有症状性先天性 CMV 疾病的婴儿进行治疗的早期研究，以确定是否治疗对听力和发育结果的益处持续到 2 岁并持续到随后的岁月十年。该研究被称为 CASG 112 试验，由抗病毒合作研究组进行并在 2008 年至 2011 年间招募了 109 名受试者。据记录，为期 6 个月的治疗与 6 周相比，有症状的先天性 CMV 提供了更好的听力和发育结果抗病毒治疗，并且这些益处持续到 2 岁。然而，不知道的是这些益处是否会持续更长时间，以及是否存在任何长期毒性在生命早期就接受缬更昔洛韦治疗。之前参加 CASG 112 研究的受试者即将迎来 12 岁生日。我们将带他们当他们 12 岁时进行听力和发育评估。返回的科目也将进行青春期评估，作为早期缬更昔洛韦治疗潜在性腺毒性的标志，以及询问任何癌症的发展。这项研究的结果将很重要。如果这些对听力和发育的益处是持久的，建议治疗时间不需要超过 6 个月。另一方面，如果有好处 6 个月的治疗并不持久（即，如果它们随着时间的推移而减弱），这具有同等价值，因为它阐明了需要进行的下一项研究，以评估可能 12 个月（甚至更长），添加或不添加第二种抗病毒药物（如莱特莫韦）。此外，如果长期毒性从早期的缬更昔洛韦疗法中被鉴定出来，这将直接影响到临床治疗有症状的先天性 CMV 疾病患者。最重要的是，可以从中获得知识按照现在的标准对长期听力和发育结果进行纵向研究治疗持续时间（6 个月）将使接受该疗程的儿童受益。