UAB researchers are involved in a new clinical trial to explore a promising treatment for adults suffering from major depressive disorder, especially for those who have not been successfully treated after trying four or more antidepressants. The study involves researchers from the Department of Psychiatry and Behavioral Neurobiology and the Department of Neurosurgery.
The study, titled “Treatment ResistAnt Depression Subcallosal CingulatE Network DBS,” or “TRANSCEND” for short, involves technology utilizing deep brain stimulation (DBS), which works by sending gentle electrical pulses to a part of the brain linked to mood regulation. This area, known as the subcallosal cingulate, has shown potential in helping people with severe depression.
“To the best of our team's knowledge, this project represents the first time an Alabama medical center has examined deep brain stimulation for depression,” said Matthew Macaluso, D.O., director of the UAB Depression and Suicide Center and Bee McWane Reid Professor in the Department of Psychiatry and Behavioral Neurobiology.
“We are thrilled to be part of the TRANSCEND clinical trial, bringing an important and promising therapy to patients with treatment-resistant depression,” added J. Nicole Bentley, M.D., associate professor in the UAB Department of Neurosurgery. “Deep brain stimulation is a minimally invasive surgery that has benefited thousands of patients with movement disorders and epilepsy, and we are proud to now bring this therapy to patients with depression and to be at the leading edge of this innovative research.”
Over the course of 12 months, the trial will enlist and involve participants from Alabama and 15 other states. For the first 12 months, Half of the participants will receive active brain stimulation and standard of care depression treatment, while the other half will receive a sham (inactive) treatment and standard of care depression treatment. Neither the participants nor the researchers will know who is receiving the active therapy during this 12-month phase of double-blind testing.
After the first year, all participants will be informed of their treatment group, and those who received the sham treatment will then be offered the active DBS therapy for an additional 2 years.
This trial represents a major step forward in finding new solutions for people living with treatment-resistant depression, and the device delivering the treatment has already received a Breakthrough Designation from the FDA—highlighting its potential to make a meaningful impact.
"This trial of deep brain stimulation for depression is an important step for patients who might benefit from a potentially lifesaving treatment for the most severe and treatment-resistant forms of depression,” Macaluso said. “Because the study device uses electrical stimulation to target specific brain regions, the project could secondarily help us better understand electrical vs chemical signaling in the brain relative to mood disorders. This might be an area of future study."
Kristine Pike, clinical research coordinator in the UAB Office of Psychiatric Clinical Research and lead coordinator of the study, hopes the trial's results will give hope to patients who may have exhausted all other options.
“This trial’s targeted patient population, those with severe treatment resistant depression, often come to us feeling as if they’re at the end of their rope,” Pike said. “They’ve exhausted all available resources to find relief—to feel joy and purpose, to feel a meaningful connection to the people and world around them. And yet, despite all of this, these patients come to us with some level of hope within them, no matter how small, that they can feel better, and their lives can improve.”
“Their hope is our chance to make an impact. It is an honor to coordinate this trial, work closely with these participants, and see if this treatment can be the key that finally unlocks long-lasting relief.”
The study is being sponsored by Abbot Medical Devices. It is registered at ClinicalTrials.gov and is expected to conclude in early 2027.