Medical Device Daily

Aspect Medical Systems (Newton, Massachusetts) has enrolled the first 20 patients in its BRITE (Biomarkers for Rapid Identification of Treatment Efficacy in Major Depression) major depression trial, designed to determine if the company's brain monitoring technology can predict the effectiveness of antidepressants after one week.

Aspect President and CEO Nassib Chamoun said during a conference call with investors and media Tuesday morning, that while most patients will “eventually respond“ to some antidepressant regimen, “it is often difficult for clinicians to predict who will respond to a particular drug, especially early in their treatment.“

Chamoun said the BRITE trial is “an ambitious effort by Aspect and our collaborating investigators to address several important clinical issues regarding the care of patients with major depression. The scale of the BRITE trial is indicative of the challenges that are faced by clinicians and researchers in determining the best course of treatment for an individual patient.“

The study is an effort to build on Aspect Medical's use of the BIS Monitoring System for central nervous system uses other than its initial focus, the monitoring of brain activity during surgery or sedation.

“As we can continue to grow our core [operating room] business and extend BIS into the ICUs and procedural sedation suite, our efforts to develop our depression and Alzheimer's disease technology represent a key part of our mid- to long-term growth strategy,“ Chamoun said.

He also said that, based on preliminary market research, a test to determine the efficacy of antidepressants after early initial use could price the test at anywhere from $100 to $250 per test. He said he expects the company's neuroscience program to “yield a product that will alter depression or Alzheimer's“ within the next three to five years.

Chamoun pointed out that “too many people suffer from major depression,“ including about 15 million just in the U.S. What has changed in dramatic fashion the treatment of people with major depression is the introduction in the 1990s of selective serotonin reuptake inhibitors, or SSRIs, as they are commonly known.

With the combination of test price and potential market for users of the test, Chamoun said, “the potential market for this technology, if effective, is clearly substantial.“

“Although newer generation antidepressants are now available in the U.S., determining which drug or combination of drugs will work for patients is still largely a trial and error process, which can last weeks or months,“ he said. “Unfortunately, many patients cannot tolerate the side effects or simply give up before receiving adequate response to treatment for their depression.“

The BRITE trial, currently enrolling patients at most of its eight trial sites, is open to women ages 21-75 who have been diagnosed with major depression, the most recent episode lasting two or more weeks, and who are not currently on a stable medication regimen.

Participants in the trial will be evaluated, placed on an FDA-approved medication – Lexapro, Wellbutrin XL or a combination – and closely monitored for 13 weeks. During nine of those weeks, there will be office visits that involve a brief EEG recording.

The study is blinded so that neither physicians nor participants will have access to the individual processed EEG results until the conclusion of the nationwide trial.

Andrew Leuchter, MD, professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior atUCLA (Los Angeles) and principal investigator for the trial, “has reported positive results in a series of proof of principal studies demonstrating that monitoring the EEG response during the first week of antidepressant treatment can provide useful predictive information concerning eventual clinical response,“ Chamoun said.

Leuchter, who focuses on assessing brain response to treatment, said during the call, “in designing the BRITE trial, we've set out to achieve a number of important and complementary objectives.“

In addition to looking at brain function, “we will look both at clinical improvement measured using standardized clinical rating scales such as the Hamilton Depression Rating Scale to achieve reactions as well as adverse reactions such as emergence of increase in suicidal ideation,“ or thoughts of suicide.

The second major objective of the study is to determine the significance of a negative EEG predictor after one week of treatment and ascertain whether this can predict which patients would “do better with a switch to a different antidepressant vs. the addition of a second antidepressant.“

“This knowledge will help us to define the most appropriate next step once a patient has been identified as being a likely non-responder to one particular drug based on brain function alone,“ Leuchter said.

The third objective of BRITE is “to determine whether the early brain response can be used to predict eventual clinical response following change in antidepressant dose levels,“ he said.

Aspect is hoping that the BRITE trial can build on the findings of a study by the National Institutes of Health (Bethesda, Maryland), called STAR*D (Sequenced Treatment Alternatives to Relieve Depression). The STAR*D trial evaluated more than 4,000 depressed patients to determine how to better manage patients who fail to respond to a standard treatment with an SSRI by defining which subsequent treatment strategies provide the best results with the least side effects, the company said.

Maurizio Fava, MD, associate chief of psychiatry for both clinical research at Massachusetts General Hospital and professor of psychiatry at Harvard Medical School (both Boston), is participating in both trials. Fava termed STAR*D the “largest clinical trial for depression ever conducted in the U.S.“

The STAR*D study found that patients who did achieve remission required six to seven weeks of treatment, with 40% of remitters taking a “full 14 weeks to feel relief from symptoms.“

But the main benefit of Aspect's success with the BRITE trial would be for clinicians and patients with major depression, who together often struggle to find the right combination of drugs to fight this crippling condition.

“If the Aspect biomarker technology can reliably determine if a patient is unlikely to respond after only one week, several weeks of ineffectiveness and suffering may be avoided,“ Fava said.