Northstar Neuroscience (Seattle) last week reported what it called “promising” initial data from an eight-patient feasibility study, called the CHESTNUT study, of its cortical stimulation treatment to treat Broca’s aphasia resulting from stroke.
The study’s principal investigators found that investigational cortical stimulation in combination with “intensive” speech/language therapy may result in greater language improvement for chronic Broca’s aphasia than speech-language therapy alone.
“We think the results are very encouraging,” John Bowers, executive vice president of Northstar Neuroscience, told Medical Device Daily.” We did the study in order to give an indication of safety, and also to indicate the feasibility of doing this for stroke survivors that have aphasia.
Aphasia, essentially damage to the brain which may produce disjointed and labored expression, affects about one million people in the U.S., largely as a result of stroke, he said.
Bowers said that with only eight patients, it was a “small study” — but “we did see very significant improvement in key measures of speech and language performance in patients who underwent the cortical stimulation.”
As a sort of pacemaker for the brain, the Northstar treatment involves a small electric pulse generator implanted near the collarbone. Wiring leads from that generator, traveling under the skin of the neck into the area of the brain where a small stimulator is placed, not in the brain, but on the outer layer, the dura.
Cortical stimulation therapy involves the “precise delivery of low levels of electricity to the outer layer of the brain via an implanted stimulator system,” according to the company.
Bowers said cortical stimulation, as developed by the company, develops a “treatment team,” with a neurosurgeon implanting the device and speech therapists having responsibility for the further management of the aphasia.
CHESTNUT was conducted by Steven Small, MD, PhD, of the Department of Neurology of the University of Chicago , and Leora Cherney, PhD, of the Rehabilitation Institute of Chicago’s Center for Aphasia Research .
Those investigators completed patient enrollment in June. Patients were randomly assigned to investigational and control groups, matched by severity of aphasia. Over a six-week period, all participants received intensive speech and language therapy. The investigational group also received cortical stimulation during the speech and language therapy sessions.
Speech and language recovery was measured using the Western Aphasia Battery-Aphasia Quotient (WAB-AQ). A five-point improvement from baseline is considered a successful outcome, the company said. Northstar said that for all CHESTNUT participants, WAB-AQ assessments were performed at various points during the study to assess changes.
The investigational group showed a mean WAB-AQ improvement from baseline to 8 points, both immediately post-therapy and at the six-week follow-up, compared to 4.6 points and 5.5 points in the control group, respectively.
Follow-up data at 12 weeks is available for six of the eight patients and “indicates that a greater increase occurred” in the investigational group, with a mean change of 12.4 points vs. a 4.1 point change in the control group.
“Importantly, these were all people who had had the stroke at least a year earlier,” Bowers said. “So, there’s a natural process of improvement that people generally go through following a stroke that’s called neuroplasticity, where the brain reorganizes in response to the injury from the stroke and other areas of the brain attempt to compensate and effectively pick up that function.”
In people with aphasia, that requires, he said, “weeks and months . . . even years of speech therapy in an effort to improve.” That makes the results achieved in the CHESTNUT study “even more striking,” Bowers said.
The company will also look at the long-term outcomes of the patients in the study, beyond the initial outcomes that have been reported. The company will consider the “appropriate next steps from a clinical standpoint” in conjunction with its clinical investigators.
Cherney said, “The potential for affecting cortical plasticity in patients with chronic aphasia to enhance speech-language outcomes is exciting for the field of speech and language pathology and for stroke rehabilitation in general.”
Small added, “Although data from a small group of patients must be taken with some caution, the present results are certainly provocative. The differences in primary outcome were accompanied by somewhat different patterns of brain imaging data, particularly involving the premotor areas. Taken together, these data suggest an altered neurobiological response to speech-language therapy in the presence of cortical stimulation.”
MDD reported in August successful preliminary results of the company’s EVEREST trial, a study of the cortical stimulation technology in hand and arm movement following stroke (MDD, Aug. 17, 2006).
Northstar, Bowers said, expects to “finish randomizing patients into the EVEREST pivotal study by the end of next year, with the hope that we would have all of the follow-up data through primary endpoint analyzed and read to submit to the FDA sometime during the first quarter of ’08.”
The company is considering its options related to clinical regulatory paths for Broca’s aphasia in conjunction with EVEREST. Bowers said the company may pursue a supplemental PMA to the motor function indication for the treatment for Broca’s aphasia.
A great deal is riding on the success of Northstar, given its gathering in of about $100 million in an IPO earlier this year (MDD, May, 8, 2006).