Oral sodium oxybate shows promise in treating laryngeal dystonia

Laryngeal dystonia (LD), a rare neurological disorder that severely affects a person’s ability to speak due to uncontrollable hoarseness, can have a negative impact on a person’s social, work and personal life mental health. Currently, LD is often managed with botulinum neurotoxin (Botox) injections, but this treatment is ineffective in up to 40% of patients who receive it. Now, a study conducted by researchers at Mass Eye and Ear, a member of the Mass General Brigham health system, shows that an oral drug, sodium oxybate, is more effective than a placebo in reducing the symptoms of LD in patients whose symptoms he saw better when they drank alcohol. .

Results from the phase 2b clinical trial, published on November 20 Reports of Neurologybuild on more than ten years of research inspired by anecdotal reports from patients with LD who said their symptoms improved after drinking a few alcoholic drinks. Sodium oxybate is a central nervous system agent approved by the FDA to treat patients with insomnia and sleep disorders. Sodium oxybate mimics some of the effects of alcohol.

In a trial of more than 100 patients, a single dose of sodium oxybate significantly improved the symptoms of patients with alcohol-responsive LD without causing serious side effects. The minimum effective dose of the drug was 16% of voice improvement, with an average of 41% in patients with alcohol-responsive LD. Sodium oxybate did not show significant changes from placebo in LD patients whose symptoms did not improve with alcohol.

We hear many stories of broken lives and careers from patients with laryngeal dystonia and are desperate for a new treatment. Our trial gives us hope for a new, more effective treatment that can be given to some of these patients. There is a lot of interest from the dystonia community, and we get a lot of calls from patients asking, ‘When will this drug be available?’ How can I get a prescription?'”

Kristina Simonyan, MD, PhD, Dr med, lead author, assistant chair of clinical research in the Department of Otolaryngology-Head and Neck Surgery at Mass Eye and Ear and professor of Otolaryngology-Head and Neck Surgery at Harvard Medical School.

Laryngeal dystonia, formerly known as spasmodic dysphonia, is a rare condition that affects more than 50,000 people in the US and Canada. It is more common in women than men and usually begins in the 40s, often affecting their lives. Its neurological cause is not well known, and patients take an average of 5.5 years to get a proper diagnosis. Once diagnosed, treatment options are limited to Botox injections every three to four months for life, if they work.

In previous open-label trials, Simonyan’s group showed that sodium oxybate improved voice symptoms in 82% of patients with alcohol-responsive LD. In their new study, the team sought to confirm the effectiveness of this drug in a more robust comparison against placebo using a double-blind clinical trial design.

The researchers enrolled 106 participants with LD, 50 of whom had alcohol-responsive symptoms. Alcohol response was determined by a standard alcohol challenge test using a controlled dose of vodka. Participants traveled from the US, UK and Canada to take part in the trial – proof of the joy this drug is bringing to the dystonia community. During two days, each patient received a single dose of 1.5g of sodium oxybate or a placebo that matched the taste, smell, color and appearance of the drug. The trial was conducted in a double-blind fashion, meaning that neither the patient nor the doctor knew when they received the active drug. To evaluate the effectiveness of the treatment, the team evaluated the voice symptoms of the patients before the treatment and at different times after the treatment.

Sodium oxybate was more effective than placebo in reducing symptoms in patients with alcohol-responsive LD but not in those whose symptoms did not improve with alcohol. The efficacy of sodium oxybate in alcohol-responsive LD did not differ between patients with mild to severe symptoms or those with additional vocal symptoms, such as voice tremors.

Voice symptoms in LD patients who respond to alcohol are significantly improved 40 minutes after taking the drug, and the benefits last for 5 hours. Although some patients experienced mild and temporary side effects such as nausea, dizziness and daytime sleepiness, there were no serious adverse events and there were no severe symptoms after the drug was tapered.

“Our findings suggest that sodium oxybate can be taken as needed, such as before work or a social event, so patients can adjust the treatment according to their daily needs and control their symptoms,” said Simonyan.

Looking ahead, Simonyan’s team plans to conduct a randomized phase 3 multicenter clinical trial to further evaluate the drug’s efficacy and safety in LD patients. His lab is also leading studies using artificial intelligence to determine which patients may benefit from treatment as well as alternative treatments for LD patients whose symptoms do not respond to alcohol.