Pivotal Trial Testing Multiple Therapies in ALS Now Enrolling at Third Scotland Site
MND-SMART, a pivotal platform trial designed to simultaneously test multiple treatment candidates in people with amyotrophic lateral sclerosis (ALS) and other motor neuron diseases, has opened its third clinical site in Scotland.
This type of platform trial, distinct from typical clinical trials that test a single treatment at a time, is expected to speed therapy development for these conditions.
Patients living in the U.K. now are being recruited at the Queen Elizabeth University Hospital in Glasgow, in addition to the Anne Rowling Regenerative Neurology Clinic in Edinburgh, and the Clinical Research Centre at Ninewells Hospital in Dundee. More centers are planned to open across the U.K.
“The MND-SMART trial launching in Glasgow is some good news at a time when there isn’t much around,” George Gorrie, MD, consultant neurologist and lead for motor neuron disease at NHS Greater Glasgow and Clyde, said in a press release.
“The pandemic and ensuring practices are COVID-19 compliant will impact how quickly people can be recruited to the trial but we are delighted to be able to start seeing participants,” Gorrie said.
MND-SMART (NCT04302870) is expected to enroll up to 750 adults with motor neuron diseases, including ALS, primary lateral sclerosis, and progressive muscular atrophy. Motor neuron diseases are a group of progressive neurological disorders caused by the loss of motor neurons, the specialized nerve cells that control voluntary movement.
Patients interested in participating in MND-SMART can register their interest here. As clinical sites open, the local trial team contacts people in the area who have signed up to find out if they are still interested in participating.
The trial will start by evaluating the effects of Allergan’s Namenda (memantine) and trazodone (sold as Desyrel, Oleptro, among others) — two therapies approved for other conditions — against a matching placebo.
This repurposing of already-approved treatments avoids some of the lengthy approval processes associated with new therapies, potentially shortening the time taken for them to become available to people with motor neuron disease.
Namenda, an oral treatment approved for Alzheimer’s disease, works by blocking the action of glutamate, the main excitatory chemical brain messenger, whose levels are higher-than-normal in several diseases, including Alzheimer’s and ALS.
Of note, excitatory signaling from one nerve cell to the next makes the latter more likely to fire an electrical signal, while inhibitory signaling makes it less likely to fire.
By normalizing glutamate levels, Namenda is expected to restore the balance of excitatory and inhibitory signals in the brain, ultimately leading to clinical improvements or preventing further damage.
Trazodone is an oral medicine approved for depression, but it also may be used for insomnia, anxiety, and panic attacks. It works in a way similar to the selective serotonin reuptake inhibitors class of antidepressants, which also are used to treat pseudobulbar affect in ALS patients.
Participants will be assigned randomly to receive an oral solution of either Namenda, trazodone, or a placebo, once a day for about one and a half years.
The trial’s main goal is to assess changes in patients’ disease progression — using the ALS Functional Rating Scale Revised score — and survival. Secondary goals include changes in cognition and behavior, respiratory function, anxiety and depression, clinical stage, and quality of life.
Based on continuous review of updated scientific evidence, new treatments can be added to the trial over its duration, while therapies proven ineffective can be dropped.
Launched in January, MND-SMART is being led by researchers at University of Edinburgh’s Euan MacDonald Centre (EMC) and funded by the EMC, substantial private donations, MND Scotland, and the My Name’5 Doddie Foundation.
Until August, more than 1,000 people with motor neuron diseases from across the U.K. had registered their interest in taking part in MND-SMART, and additional research teams showed interest in becoming a trial site. More information about the trial can be found here.