背景:戈谢病3型(GD3)是一种遗传性疾病,以内脏表现和慢性神经系统症状为特征的进行性溶酶体贮积症(例如,水平眼肌麻痹/核上凝视麻痹,共济失调,肌张力障碍)。研究药物venglustat正在与imiglucerase联合研究,作为单臂GD3的系统性和神经病性表现的潜在治疗方法,开放标签,2期试验(LEAP;N=11)。从患者的角度了解GD3症状的感知变化,看护者,和临床医生,我们对选定的LEAP参与者进行了定性案例研究.
方法:四名LEAP患者(年龄范围,20-28岁),他们的四个看护人,主持人使用半结构化指南对参与LEAP的3名临床医师进行了单独访谈.临床医生的看法是基于对受访患者和未接受采访的LEAP患者的观察,以及参与LEAP的其他工作人员提供的信息,病人,和照顾者。
结果:报告的GD3症状变化因患者和报告者而异。至少有一名患者自发地提到只有眼球运动得到改善,看护人,临床专家。症状改善在改善时间方面也有所不同。在最初的几周内,在理解新信息或复杂指令方面有所改善,记住工作日,眼球运动,震颤,和癫痫发作。警觉性的变化,参与度和响应能力,记忆,浓度在几个月或一年后出现。大多数护理人员和所有临床专家报告了更大的患者独立性(例如,在试验期间独立进行日常生活或旅行活动的能力增强)作为对GD3影响的感知治疗效果。对于一位感觉到venglustat疗法有益的患者,LEAP期间的药代动力学分析发现,血浆和脑脊液中的venglustat水平低至无法检测到。
结论:这项研究的结果提供了对GD3症状和venglustat治疗期间报告的早期信号变化的见解。
背景:ClinicalTrials.gov标识符,NCT02843035。
BACKGROUND: Gaucher disease type 3 (GD3) is a genetic, progressive lysosomal storage disorder characterized by visceral manifestations and chronic neurologic symptoms (e.g., horizontal ophthalmoplegia/supranuclear gaze palsy, ataxia, dystonia). The investigational agent venglustat is being studied in combination with imiglucerase as potential treatment for systemic and neuronopathic manifestations of GD3 in a single-arm, open-label, phase 2
trial (LEAP; N = 11). To understand perceived changes in GD3 symptoms from the perspectives of patients, caregivers, and clinicians, we conducted a qualitative case
study of selected LEAP participants.
METHODS: Four patients in LEAP (age range, 20-28 years), four of their caregivers, and three clinicians involved in LEAP were interviewed individually by moderators using semi-structured guides. Clinicians\' perceptions were based on observation of interviewed patients and those in LEAP who were not interviewed, as well as information provided by other staff involved in LEAP, patients, and caregivers.
RESULTS: Reported changes in GD3 symptoms varied among patients and among reporters. Only eye movement was spontaneously mentioned as improved by at least one patient, caregiver, and clinical expert. Symptom improvement also varied in terms of time to improvement. Within the first weeks, improvements were seen in understanding new information or complex instructions, remembering the weekday, eye movement, tremor, and seizures. Changes in alertness, engagement and responsiveness, memory, and concentration appeared after months or a year. Most caregivers and all clinical experts reported greater patient independence (e.g., increased ability to perform activities of daily living or travel independently during the
trial) as a perceived treatment effect on a GD3 impact. For one patient who perceived benefits from venglustat therapy, pharmacokinetic analyses during LEAP found low to undetectable venglustat levels in their plasma and cerebrospinal fluid.
CONCLUSIONS: Outcomes from this
study provide insights into GD3 symptoms and the early signaling of changes reported during venglustat therapy.
BACKGROUND: ClinicalTrials.gov identifier, NCT02843035.