San Francisco,
California
94143
Purpose:
Neurons are specialized types of cells that are responsible for carrying out the functions of
the brain. Neurons communicate with electrical signals. In diseases such as major depression
this electrical communication can go awry. One way to change brain function is using
electrical stimulation to help alter the communication between groups of neurons in the
brain.
The purpose of this study is to test a personalized approach to brain stimulation as an
intervention for depression. The study researchers will use a surgically implanted device to
measure each individual's brain activity related to his/her depression. The researchers will
then use small electrical impulses to alter that brain activity and measure whether these
changes help reduce depression symptoms. This study is intended for patients with major
depression whose symptoms have not been adequately treated with currently available
therapies.
The device used in this study is called the NeuroPace Responsive Neurostimulation (RNS)
System. It is currently FDA approved to treat patients with epilepsy. The study will test
whether personalized responsive neurostimulation can safely and effectively treat depression.
Study summary:
This is a single-center 3-stage feasibility study of personalized closed-loop stimulation for
treatment resistant Major Depressive Disorder. Depending on participant's results at each
stage, he/she might not be eligible to proceed to all 3 stages.
Stage 1 of the study will involve surgically implanting small, thin electrodes in brain
regions that regulate depression in order to identify personalized treatment sites. The
researchers will test stimulation in the different brain regions and their effect on
depression symptoms. The electrodes will be surgically removed at the end of Stage 1.
Stage 2 will involve a second brain surgery to implant the NeuroPace RNS® System. Researchers
will use information from Stage 1 to decide where to implant the electrodes of the RNS
System. Over the next ~4-12 months, participants will have regular study visits in the clinic
where the researchers will determine a personalized brain activity pattern that correlates
with depression symptoms and can be paired with stimulation to improve depression symptoms.
Stage 3 will be 12 months long and will involve turning ON and OFF the intervention to test
its effectiveness. Over the course of a year, the participant will have two 6-week periods
with no stimulation and will receive the intervention for the remainder of the time.
At the end of this stage the participant can choose to continue with long-term follow-up or
have the RNS System surgically removed.
Criteria:
Inclusion Criteria:
- Age 22-70
- Meet the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic
criteria for Major Depressive Disorder (MDD) without psychosis based on a Structured
Clinical Interview for DSM-V (SCID) with current episode ≥ 2 years that is treatment-
resistant (4 adequate trials (including ECT), 3 classes of medications, one
augmentation strategy, psychotherapy) as measured by the antidepressant treatment
history form (ATHF).
- Failed electroconvulsive therapy (ECT) due to inability to achieve sustained response
(2 failed attempts to discontinue ECT treatment) or discontinued due to intolerable
side effects.
- Has MADRS score of > 26 at both baseline and screening visit
- The presence of variability on repeated administrations of MDD rating scales (minimum
of 2-point variation on the HAMD-6 administered 3 times a day for 3 days), which is
required for the identification of a neural biomarker.
- If patient is on a regimen of psychotropic medication, no changes in this regimen
should be made during the 4 weeks prior to entry into and the duration of the study.
- Willing and able to undergo invasive brain recording/stimulation study
- Willing and able to attend multiple research visits and perform at-home research
protocol
- Willing and able to provide informed consent
- Ability to speak and read English
Exclusion Criteria:
- Meets DSM-V criteria for a psychotic disorder, eating disorder, panic disorder,
posttraumatic stress disorder, bipolar disorder, obsessive compulsive disorder, tic
disorder, or another comorbid psychiatric disorder other than MDD or generalized
anxiety disorder based on a SCID
- Generalized anxiety disorder is the primary DSM-V disorder during the current MDD
episode
- Active suicidal ideation with intent and plan as defined by a score of 5 on the
Columbia-Suicide Severity Rating Scale (C-SSRS)
- History of suicide attempt requiring hospitalization in previous 2 years.
- Meets criteria for alcohol or substance abuse or dependence (other than caffeine) in
previous 6 months, determined by the SCID
- Has a personality disorder based on the investigator's assessment that the
investigator believes will adversely impact subject compliance or safety
- Fibromyalgia or chronic fatigue syndrome
- Current condition requiring chronic narcotic use
- History of traumatic brain injury, another neurological disorder, or developmental
delay
- History of seizures
- MRI (done within one year of the first visit) with significant abnormalities
- Previous ablative intracranial surgery or previously implanted deep brain stimulation
system or any previously implanted device treatment involving brain stimulation
- Implantable hardware not compatible with MRI or with the study
- Major medical co-morbidities increasing the risk of surgery including severe diabetes,
major organ system failure, history of hemorrhagic stroke, need for chronic
anticoagulation other than aspirin, active infection, intracranial space occupying
lesion, increased intracranial pressure, cardiovascular accident within the last
month, aneurysm/abnormality, retinal detachment, unstable cardiovascular disease
(recent myocardial infarction, severe ischemia, severe or uncontrolled hypertension),
immunocompromised state, or malignancy with < 5 years life expectancy
- Inability to stop Coumadin or platelet anti-aggregation therapy for surgery and after
surgery. - Patients taking these medications will need to discuss the need/risk of
continuing these medications with their physicians and the PI or study personnel may
contact the treating physician(s) to discuss the risks of
anticoagulation/antiaggregation therapy discontinuation
- Coagulopathy. Patients will be excluded unless assessed and cleared by hematology
- Allergies or known hypersensitivity to materials in the NeuroPace RNS® System (i.e.
titanium, polyurethane, silicone, polyetherimide, stainless steel)
- Subject lives alone without possibility of caregiver support post-hospital stay
- Inability to comply with study follow-up visits
- Women who are pregnant, plan to become pregnant, or breast feeding
- Inability to speak and/or read English
- Inability to give consent
- Significant cognitive impairment or dementia (MoCA < 25)
- Likely to require ECT during the course of the study