Payne Jonathan M, Barton Belinda, Ullrich Nicole J, Cantor Alan, Hearps Stephen J C, Cutter Gary, Rosser Tena, Walsh Karin S, Gioia Gerard A, Wolters Pamela L, Tonsgard James, Schorry Elizabeth, Viskochil David, Klesse Laura, Fisher Michael, Gutmann David H, Silva Alcino J, Hunter Scott J, Rey-Casserly Celiane, Cantor Nancy L, Byars Anna W, Stavinoha Peter L, Ackerson Joseph D, Armstrong Carol L, Isenberg Jill, O'Neil Sharon H, Packer Roger J, Korf Bruce, Acosta Maria T, North Kathryn N
From the Murdoch Children's Research Institute (J.M.P., S.J.C.H., K.N.N.), Royal Children's Hospital; Department of Paediatrics (J.M.P., K.N.N.), Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne; Children's Hospital Education Research Institute (B.B.), Children's Hospital at Westmead; Discipline of Paediatrics and Child Health (B.B.), University of Sydney, Australia; Department of Neurology (N.J.U., C.R.-C.), Boston Children's Hospital, MA; Department of Preventative Medicine (A.C.), School of Public Health (G.C.), Department of Psychology (J.D.A.), and Department of Genetics (B.K.), University of Alabama at Birmingham; Department of Neurology (T.R., S.H.O.), Children's Hospital of Los Angeles, CA; Center for Neuroscience and Behavioral Medicine (K.S.W., G.A.G., R.J.P., M.T.A.), Children's National Health System, Washington, DC; Pediatric Oncology Branch Center for Cancer Research (P.L.W.), National Cancer Institute, Bethesda, MD; Division of Neurology (J.T., S.J.H.), University of Chicago Medicine Comer Children's Hospital, IL; Human Genetics (E.S.) and Division of Neurology (A.W.B.), Cincinnati Children's Hospital Medical Center, OH; Department of Genetics (D.V.), University of Utah, Salt Lake City; Department of Pediatrics (L.K.), University of Texas Southwestern Medical Center, Dallas; Division of Oncology (M.F., C.L.A.), Children's Hospital of Philadelphia, PA; Department of Neurology (D.H.G., J.I.), Washington University School of Medicine in St Louis, MO; Gonda Neuroscience and Genetics Center (A.J.S.), University of California Los Angeles; Primary Children's Hospital (N.L.C.), Salt Lake City, UT; and University of Texas MD Anderson Cancer Center (P.L.S.), Houston.
Neurology. 2016 Dec 13;87(24):2575-2584. doi: 10.1212/WNL.0000000000003435. Epub 2016 Nov 9.
To assess the efficacy of lovastatin on visuospatial learning and attention for treating cognitive and behavioral deficits in children with neurofibromatosis type 1 (NF1).
A multicenter, international, randomized, double-blind, placebo-controlled trial was conducted between July 2009 and May 2014 as part of the NF Clinical Trials Consortium. Children with NF1 aged 8-15 years were screened for visuospatial learning or attention deficits (n = 272); 146 children demonstrated deficits at baseline and were randomly assigned to lovastatin (n = 74; 40 mg/d) or placebo (n = 70). Treatment was administered once daily for 16 weeks. Primary outcomes were total errors on the Cambridge Neuropsychological Test Automated Battery Paired Associate Learning task (visuospatial learning) and the Score subtest from the Test of Everyday Attention for Children (sustained attention). Secondary outcomes measured executive function, attention, visuospatial skills, behavior, and quality of life. Primary analyses were performed on the intention-to-treat population.
Lovastatin had no significant effect on primary outcomes after 16 weeks of treatment: visuospatial learning (Cohen d = -0.15, 95% confidence interval -0.47 to 0.18) or sustained attention (Cohen d = 0.19, 95% confidence interval -0.14 to 0.53). Lovastatin was well tolerated, with no increase in reported adverse events compared to placebo.
Lovastatin administered once daily for 16 weeks did not improve visuospatial learning or attention in children with NF1 and is not recommended for amelioration of cognitive deficits in this population.
This study was registered at ClinicalTrials.gov (NCT00853580) and Australian New Zealand Clinical Trials Registry (ACTRN12607000560493).
This study provides Class I evidence that for children with NF1, lovastatin does not improve visuospatial learning or attention deficits.
评估洛伐他汀对1型神经纤维瘤病（NF1）患儿视觉空间学习和注意力的影响，以治疗其认知和行为缺陷。
作为NF临床试验联盟的一部分，于2009年7月至2014年5月进行了一项多中心、国际、随机、双盲、安慰剂对照试验。对年龄在8至15岁的NF1患儿进行视觉空间学习或注意力缺陷筛查（n = 272）；146名患儿在基线时表现出缺陷，并被随机分配至洛伐他汀组（n = 74；40 mg/d）或安慰剂组（n = 70）。治疗每日给药一次，持续16周。主要结局指标为剑桥神经心理测试自动成套测验配对联想学习任务（视觉空间学习）的总错误数以及儿童日常注意力测试的得分子测验（持续注意力）。次要结局指标测量执行功能、注意力、视觉空间技能、行为和生活质量。对意向性治疗人群进行主要分析。
治疗16周后，洛伐他汀对主要结局指标无显著影响：视觉空间学习（Cohen d = -0.15，95%置信区间-0.47至0.18）或持续注意力（Cohen d = 0.19，95%置信区间-0.14至0.53）。洛伐他汀耐受性良好，与安慰剂相比，报告的不良事件未增加。
每日一次服用洛伐他汀16周并未改善NF1患儿的视觉空间学习或注意力，不建议用于改善该人群的认知缺陷。
本研究已在ClinicalTrials.gov（NCT00853580）和澳大利亚新西兰临床试验注册中心（ACTRN12607000560493）注册。
本研究提供I级证据，表明对于NF1患儿，洛伐他汀不能改善视觉空间学习或注意力缺陷。
