Closed-Loop Deep Brain Stimulation for Major Depression

ConditionMajor Depressive Disorder

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 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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

Disqualifiers

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.

Trial design

Design model

Crossover

Treatments tested in this trial

Stimulation-ON
Device
Active neurostimulation from the NeuroPace RNS® System triggered by a biomarker
Stimulation-OFF
Device
No neurostimulation from the NeuroPace RNS® System
Stimulation-ON Active Control
Device
Active neurostimulation from the NeuroPace RNS® System triggered by a sham biomarker

Treatment groups

12 Participants

are divided into 3 treatment groups

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

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

Group C: Arm 3: Active Control (stimulation ON triggered by sham biomarker)Active comparator 1 intervention

Trial outcomes

Primary outcomes

change in MADRS score

Effect size of active compared to sham stimulation (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score before and after the sham and treatment periods). Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.

Time frame

administered at baseline and every 2 weeks for the first 18 weeks of stage 3

Secondary outcomes

change in Montgomery Asberg Depression Rating Scale (MADRS) score after 1 year

Effect size of active compared to sham stimulation (mean difference in Montgomery Asberg Depression Rating Scale (MADRS) score before and after the sham and treatment periods at the end of Stage 3. Higher MADRS score indicates more severe depression; the overall score ranges from 0 to 60.

Time frame

administered at Weeks 30 and every 2 weeks for the last 18 weeks of Stage 3

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

Mean difference in Hamilton Depression Rating Scale (HAMD-17) score across the two 6-week cross-over periods. 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 2 weeks for the first 18 weeks of stage 3

difference in Hamilton Depression Rating Scale (HAMD-17) score after 1 year

Mean difference in Hamilton Depression Rating Scale (HAMD-17) score across the two 6-week cross-over periods at 1 year. The score for Hamilton Depression Rating Scale ranges from 0-50, with a higher score indicating more severe depression.

Time frame

administered at Weeks 30 and every 2 weeks for the last 18 weeks of Stage 3

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

Mean difference in Inventory of Depressive Symptomatology Self-Report (IDS-SR) score across the two 6-week cross-over periods. The scores range from 0 to 27, with higher scores indicating more depressive symptoms.

Time frame

administered at baseline and every 2 weeks for the first 18 weeks of stage 3

Other outcomes

Stimulation site identification

Over 50% of patients move from Stage 1 to Stage 2 (stimulation site that acutely improved mood identified)

Time frame

Final study visit of Stage 1 (roughly 3-6 months after initial enrollment)

Biomarker identification in Stage 1

The number of patients in whom we can identify a neural biomarker that accounts for a significant amount of variance in depression symptom severity

Time frame

Final study visit of Stage 1 (roughly 3-6 months after initial enrollment)

Number of patients who had viable biomarker(s) identified in Stage 2

The number of patients in whom we can identify a neural biomarker utilizing the RNS system that accounts for a significant amount of variance in depression symptom severity

Time frame

Final study visit of Stage 2 (up to 1 year duration)

The number of patients in whom we can identify a neural biomarker utilizing the RNS system that accounts for a significant amount of variance in depression symptom severity

The number of patients in whom we can find a personalized biomarker of depression in terms of accounting for significant variance in depression

Time frame

Assessed at the final study visit of Stage 3 (1 year duration)

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

Apply now