Key Points
- A clinical trial in Spain is now enrolling participants with non-familial amyotrophic lateral sclerosis (ALS).
- The Foundation and the ALS Association are co-funding the research study, which is testing neuromodulation to slow the progression of the disease.
A two-stage pilot clinical trial is underway in Barcelona to investigate the use of focused ultrasound neuromodulation as a potential treatment for ALS – also known as Lou Gehrig’s disease. The ALS Association and the Focused Ultrasound Foundation are jointly funding this project.
In this study, titled “Modulation of the motor pathway by transcranial pulse stimulation (TPS) in people with ALS: A pilot randomized trial,” investigators will test whether TPS can be used to decrease motor cortex hyperexcitability and therefore slow the progression of ALS. TPS is a noninvasive, neuronavigation-guided form of neuromodulation that delivers ultra-short mechanical waves of low intensity focused ultrasound.
The trial (NCT 06681610) is taking place in Barcelona and being led by Pablo Villoslada, MD, chair of neurology at Hospital del Mar and director of the Neurosciences Program at Hospital del Mar Research Institute, and Alba León, MD, a neurophysiologist at Hospital del Mar. A total of 50 adult participants will be enrolled per the study’s inclusion and exclusion criteria (e.g., familial ALS is excluded). The research team will first use the Storz Medical Neurolith device to deliver the TPS.
- In Stage 1, the first 10 participants will receive six sessions of open-label TPS over a two-week period and then researchers will measure any excitability changes in the motor cortex and plasma biomarkers (neurofilament s, TDP43, and tau in extracellular vesicles of neuronal origin) from baseline to week eight.
- In Stage 2 — the randomized, double blind, sham-controlled part of the clinical study — an additional 40 participants (20 per group) will receive either the TPS treatment or a sham TPS treatment. The two groups will be compared to determine any differences in motor cortex activity.
After Stage 2 is complete, investigators will also measure changes from baseline to month 6 in the total score of the ALS functional rating scale-revised (or ALSFRS-R).
Those in the sham cohort will have the opportunity to receive TPS stimulation after a period of time to ensure all participants benefit from the clinical trial. This group’s outcomes after the crossover will not be factored into the trial results.
“ALS is a devastating disease, and any new therapeutic approach to help patients is a top priority,” said Dr. Villoslada. “Focused ultrasound and TPS provide the ability to modulate neural network functioning and eventually restore motor function. TPS’s mechanism of action works mainly through increasing blood microcirculation in the cortex. We will assess such effects using biomarkers and clinical scales.”
To date, the first seven participants have been enrolled in the clinical trial, which is expected to continue enrollment through December 2025.
In 2023, the Focused Ultrasound Foundation and the ALS Association established a partnership funding program with the goal of advancing the development of new focused ultrasound applications for the treatment and diagnosis of ALS. The organizations each extended up to $500,000 in funding to support research projects that address critical unanswered questions to treat ALS patients. Noninvasively modulating the motor cortex with the goal of improving function in patients with ALS was specified as an area of interest for the partnership.
For Patients
If you are interested in learning more about this clinical trial, please contact:
Alba León, MD
+34932 48 30 00
aleonjorba@hmar.cat
Sergio Vidal, MD
+34932 48 30 00
sergio.vidal.notari@hmar.cat