Researchers have conducted a clinical trial on a medication that replicates the effects of alcohol, involving over 100 patients suffering from laryngeal dystonia—a neurological disorder characterized by involuntary muscle spasms in the larynx, which can severely affect a person’s voice. The trial was prompted by patients’ experiences, noting that their symptoms appeared to lessen after drinking alcohol.
Laryngeal dystonia (LD) is a rare neurological condition that severely impacts a person’s ability to speak due to uncontrollable spasms in the vocal cords. This can significantly hinder an individual’s social activities, work life, and mental wellbeing. Currently, LD treatments primarily involve botulinum neurotoxin (Botox) injections; however, about 40% of patients do not find relief from this approach. A new study led by researchers at Mass Eye and Ear, part of the Mass General Brigham healthcare network, reveals that sodium oxybate, an oral medication, is more effective than a placebo in alleviating LD symptoms for those who find temporary symptom relief from alcohol.
The findings from the phase 2b randomized clinical trial were published on November 20th in Annals of Neurology. This research builds on over ten years of investigation, prompted by anecdotal evidence from patients indicating their symptoms improved after they had a drink. Sodium oxybate, a medication approved by the FDA for treating narcolepsy and sleep disorders, mimics several effects of alcohol.
In the trial involving more than 100 participants, a single dose of sodium oxybate significantly alleviated the symptoms of patients who respond to alcohol, without resulting in serious side effects. The minimum observed improvement in voice was 16%, while the average improvement was 41% for those with alcohol-responsive LD. However, sodium oxybate did not show notable effects compared to placebo in patients whose symptoms did not respond to alcohol.
Kristina Simonyan, MD, PhD, Dr med, the lead author and vice chair for clinical research in the Otolaryngology-Head and Neck Surgery Department at Mass Eye and Ear as well as a professor at Harvard Medical School, commented, “We hear countless stories about how laryngeal dystonia has shattered lives and careers, and there is an urgent need for new therapies. Our study gives hope for an effective treatment option for some patients.” She added, “The dystonia community is highly interested, and we frequently receive inquiries from patients asking when this drug will be available and how they can obtain a prescription.”
Formerly known as spasmodic dysphonia, laryngeal dystonia is a rare condition that affects over 50,000 individuals in the US and Canada. It is more prevalent among women and usually manifests in the 40s, often severely compromising their quality of life. The precise neurological cause remains unidentified, and it often takes patients an average of 5.5 years to receive a proper diagnosis. Once diagnosed, options are limited, typically requiring Botox injections every three to four months for life, if they prove effective.
In earlier open-label studies, Simonyan’s team found that sodium oxybate improved voice symptoms in 82% of patients with alcohol-responsive LD. The new study aimed to confirm the drug’s effectiveness through a more structured comparison with a placebo using a double-blind randomized clinical trial approach.
The research team enrolled 106 LD patients, 50 of whom had symptoms responsive to alcohol. Their alcohol responsiveness was assessed using a standardized test involving a controlled amount of vodka. Participants traveled from various locations across the U.S., UK, and Canada to take part in the study, highlighting the enthusiasm within the dystonia community regarding this potential treatment. Over two days, each patient received either 1.5g of sodium oxybate or a taste-matched placebo. The double-blind approach ensured that neither the patients nor the clinicians knew who received the actual drug. The effectiveness of the treatment was gauged by evaluating patients’ voice symptoms before treatment and at several intervals after treatment.
Sodium oxybate was found to be significantly better than the placebo in mitigating symptoms for patients with alcohol-responsive LD but had no effect on those whose symptoms did not respond to alcohol. The efficacy of sodium oxybate was consistent across patients with varying levels of symptom severity (mild to severe) and those who had additional vocal issues, such as tremors.
Improvements in voice symptoms were observed about 40 minutes after taking the drug, with effects lasting for up to five hours. Some patients did report mild and temporary side effects like nausea, dizziness, and drowsiness during the day, but no serious adverse events occurred, and there was no worsening of symptoms after the medication wore off.
Simonyan noted, “Our results indicate that sodium oxybate can be used as needed, for instance, before work or social outings, allowing patients to customize their treatment based on daily requirements and gain control over their symptoms.”
Looking ahead, Simonyan’s team plans to initiate a phase 3 multi-site randomized clinical trial to further evaluate the drug’s effectiveness and safety in LD patients. Additionally, her lab is conducting studies employing artificial intelligence to identify which patients might benefit most from this treatment, as well as exploring alternative options for those whose symptoms do not respond to alcohol.
