Efficacy and Safety of Sodium Oxybate in Isolated Focal Laryngeal Dystonia: A Phase IIb Double-Blind Placebo-Controlled Cross-Over Randomized Clinical Trial.

IF 8.1 1区 医学 Q1 CLINICAL NEUROLOGY
Kristina Simonyan, Lena C O'Flynn, Azadeh Hamzehei Sichani, Steven J Frucht, Anna F Rumbach, Nutan Sharma, Phillip C Song, Alexis Worthley
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Abstract

Objective: To examine the efficacy and safety of sodium oxybate versus placebo in a phase IIb randomized double-blind placebo-controlled 2-period cross-over clinical trial in patients with isolated laryngeal dystonia (LD).

Methods: The study was conducted from January 2018 to December 2021, pausing during the COVID-19 pandemic, at Massachusetts Eye and Ear in 106 patients with alcohol-responsive (EtOH+) and alcohol-non-responsive (EtOH-) LD (53 to receive 1.5g of sodium oxybate first, 53 to receive matching placebo first). The primary outcome was a change from baseline in LD symptom severity 40 minutes after drug intake. Safety was based on vital signs, cognitive function, suicidality, daytime sleepiness, and adverse events. Patients, investigators, and outcome assessors were masked to study procedures.

Results: Compared to baseline, EtOH+ but not EtOH- patients had a statistically significant improvement in LD symptoms following sodium oxybate versus placebo (EtOH+: 98.75% confidence interval [CI] = 0.6-26.9; p = 0.008; EtOH-: 98.75% CI = -6.2 to 18.7; p = 0.42). Statistically significant minimum drug efficacy in EtOH+ patients was found at ≥16% symptom improvement (OR = 2.09; 98.75% CI = 0.75-5.80; p = 0.036), with an average of 40.81% benefits (98.75% CI = 34.7-48.6). Drug efficacy waned by 300 minutes after intake without a rebound. No changes were found in cognitive function, suicidality, or vital signs. Common adverse events included mild dizziness, nausea, and daytime sleepiness.

Interpretation: Sodium oxybate showed clinically meaningful improvement of symptoms in EtOH+ LD patients, with acceptable tolerability. Sodium oxybate offers the first pathophysiologically relevant oral treatment for laryngeal dystonia. ANN NEUROL 2024.

羟苯磺酸钠对孤立性局灶性喉肌张力障碍的疗效和安全性:IIb期双盲安慰剂对照交叉随机临床试验》。
目的在一项针对孤立性喉肌张力障碍(LD)患者的IIb期随机双盲安慰剂对照2期交叉临床试验中,考察羟苄酸钠与安慰剂的疗效和安全性:该研究于2018年1月至2021年12月在马萨诸塞州眼耳科医院进行,在COVID-19大流行期间暂停,研究对象为106例酒精反应性(EtOH+)和酒精无反应性(EtOH-)LD患者(53例先接受1.5克氧贝特钠,53例先接受匹配的安慰剂)。主要结果是服药 40 分钟后 LD 症状严重程度与基线相比的变化。安全性基于生命体征、认知功能、自杀倾向、白天嗜睡和不良事件。患者、研究人员和结果评估人员均对研究过程蒙蔽:与基线相比,服用羟苯磺酸钠和安慰剂后,EtOH+ 患者的 LD 症状有显著改善(EtOH+:98.75% 置信区间 [CI] = 0.6-26.9;P = 0.008;EtOH-:98.75% 置信区间 [CI] = -0.6-26.9;P = 0.008):98.75%置信区间 = -6.2 至 18.7;p = 0.42)。EtOH+患者的最低药物疗效在症状改善≥16%时具有统计学意义(OR = 2.09; 98.75% CI = 0.75-5.80; p = 0.036),平均获益率为 40.81% (98.75% CI = 34.7-48.6)。服药 300 分钟后药效减弱,但无反弹。认知功能、自杀倾向或生命体征均无变化。常见不良反应包括轻度头晕、恶心和白天嗜睡:解释:羟苯酸钠对EtOH+ LD患者的症状有临床意义的改善,且耐受性可接受。奥昔贝特钠为喉肌张力障碍提供了第一种病理生理学相关的口服治疗方法。ann neurol 2024.
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来源期刊
Annals of Neurology
Annals of Neurology 医学-临床神经学
CiteScore
18.00
自引率
1.80%
发文量
270
审稿时长
3-8 weeks
期刊介绍: Annals of Neurology publishes original articles with potential for high impact in understanding the pathogenesis, clinical and laboratory features, diagnosis, treatment, outcomes and science underlying diseases of the human nervous system. Articles should ideally be of broad interest to the academic neurological community rather than solely to subspecialists in a particular field. Studies involving experimental model system, including those in cell and organ cultures and animals, of direct translational relevance to the understanding of neurological disease are also encouraged.
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