Closed-Loop Deep Brain Stimulation for Treatment-Resistant Bipolar Depression

ConditionsBipolar II Disorder Bipolar II Disorder, Most Recent Episode Major Depressive

Trial statusRecruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age22-70

SponsorAndrew Krystal

About this trial

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 bipolar 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 bipolar depression.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Age 22-70

Meet Diagnostic and Statistical Manual-V (DSM-V) diagnostic criteria for Bipolar II Disorder, with an episode of depression lasting at least 1 year that is treatment resistant as defined above, without a manic or hypomanic episode in the last 2 years; patients must be taking a mood stabilizer (lithium >0.6 mEq/L or valproate >350 mM/L), an atypical antipsychotic, or a combination of a mood stabilizer and an atypical antipsychotic for at least 2 weeks at a stable dosage before starting the study and must continue taking anti-manic medication throughout their participation in the study unless discontinuation is necessary because of patient safety/health considerations.

Must have either failed ECT (it was effective but not tolerated due to side effects; it was effective, but patients could not achieve a sustained response), not been able to complete a course of ECT due to side effects, or have been medically advised to receive ECT and have been unwilling or unable to obtain ECT.

Has MADRS score of > 26 at two baseline visits

Disqualifiers

Meets DSM-V criteria for a psychotic disorder, eating disorder, panic disorder, posttraumatic stress 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.

Trial design

Design model

Crossover

Treatments tested in this trial

Device: Stimulation-ON
Device
Active neurostimulation from the NeuroPace RNS® System triggered by a biomarker
Device: Stimulation-OFF
Device
No neurostimulation from the NeuroPace RNS® System
Device: Stimulation -ON Active Control
Device
Active neurostimulation from the NeuroPace RNS® System triggered with a fixed duty cycle

Treatment groups

10 Participants

are divided into 3 treatment groups

Group A: Experimental: Arm 1: Intervention (stimulation ON)Experimental treatment 1 intervention

Group B: Sham Comparator: Arm 2: Sham Control (stimulation OFF)Sham comparator 1 intervention

Group C: Active Comparator: Arm 3: Active Control (stimulation ON fixed intermittent)Active comparator 1 intervention

Trial outcomes

Primary outcomes

Change in Montgomery-Asberg Depression Rating Scale (MADRS) score

Effect size comparing closed-loop stimulation, open-loop (fixed intermittent) stimulation, and sham stimulation (MADRS score before and after each treatment period of the crossover). Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.

Time frame

Administered twice at baseline and every 2 weeks for the 36-40 weeks of Stage 3

Secondary outcomes

Change in Hamilton Depression Rating Scale (HAMD-17) score

Effect size comparing closed-loop stimulation, open-loop (fixed intermittent) stimulation, and sham stimulation (HAMD-17 score before and after each treatment period of the crossover). The score for Hamilton Depression Rating Scale ranges from 0-50, with a higher score indicating more severe depression.

Time frame

Administered at baseline and every 4 weeks for the 36-40 weeks of Stage 3

Change in the Inventory of Depressive Symptomatology Self-Report (IDS-SR) score

Effect size comparing closed-loop stimulation, open-loop (fixed intermittent) stimulation, and sham stimulation (IDS-SR score before and after each treatment period of the crossover). The scores range from 0 to 27, with higher scores indicating more depressive symptoms.

Time frame

Administered at baseline and every 4 weeks for the 36-40 weeks of Stage 3

Other outcomes

Daily stimulation events

Number of daily stimulation events

Time frame

Up to 24 weeks

Stimulation duration

Cumulative stimulation duration per day

Time frame

Up to 24 weeks

Stimulation site identification

The number of patients that move from Stage 1 to Stage 2 (stimulation site identified that acutely improved symptoms)

Time frame

Decision made in the 1-3 months following Stage 1

Biomarker identification in Stage 1

Number of patients in whom we can identify a neural biomarker

Time frame

Decision made in the 1-3 months following Stage 1

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Andrew Krystal

Lead sponsor

University of California, San Francisco

Sponsor institution

Source ClinicalTrials.gov

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