TY - JOUR
T1 - Efficacy and Safety of Sodium Oxybate in Isolated Focal Laryngeal Dystonia
T2 - A Phase IIb Double-Blind Placebo-Controlled Cross-Over Randomized Clinical Trial
AU - Simonyan, Kristina
AU - O'Flynn, Lena C.
AU - Hamzehei Sichani, Azadeh
AU - Frucht, Steven J.
AU - Rumbach, Anna F.
AU - Sharma, Nutan
AU - Song, Phillip C.
AU - Worthley, Alexis
N1 - Publisher Copyright:
© 2024 The Author(s). Annals of Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
PY - 2024
Y1 - 2024
N2 - 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 2025;97:329–343.
AB - 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 2025;97:329–343.
UR - http://www.scopus.com/inward/record.url?scp=85209674442&partnerID=8YFLogxK
U2 - 10.1002/ana.27121
DO - 10.1002/ana.27121
M3 - Article
AN - SCOPUS:85209674442
SN - 0364-5134
VL - 97
SP - 329
EP - 343
JO - Annals of Neurology
JF - Annals of Neurology
IS - 2
ER -