Closed-Loop Deep Brain Stimulation for Major Depression

NCT04004169 | Recruiting DMC FDA Device

• 1 other identifier: 17-23724
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Major Depressive Disorder

Keywords

Major Depressive Disorder; Depression; Treatment-resistance; Deep brain stimulation; Closed-loop; Biomarker; Responsive neurostimulation; Brain surgery

Outcome Measures

Primary Outcomes (1)

• 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.

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

Secondary Outcomes (5)

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

  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

  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

  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

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

• difference in Inventory of Depressive Symptomatology Self-Report (IDS-SR) score after 1 year

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

Other Outcomes (8)

• Stimulation site identification

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

• Biomarker identification in Stage 1

  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

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

Study Arms (3)

Arm 1: Intervention (stimulation ON)

EXPERIMENTAL

This is a crossover trial. Each patient will receive 6 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and Stimulation ON Active Control (sham biomarker) (arm 3) in random order. After 6 months of intervening therapy, this 3-period crossover study will be repeated.

Device: Stimulation-ON

Arm 2: Sham Control (stimulation OFF)

SHAM COMPARATOR

This is a crossover trial. Each patient will receive 6 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and Stimulation ON Active Control (sham biomarker) (arm 3) in random order. After 6 months of intervening therapy, this 3-period crossover study will be repeated.

Device: Stimulation-OFF

Arm 3: Active Control (stimulation ON triggered by sham biomarker)

ACTIVE COMPARATOR

This is a crossover trial. Each patient will receive 6 wks of stimulation ON (arm 1), stimulation OFF (arm 2), and stimulation ON Active Control (sham biomarker) (arm 3) in random order. After 6 months of intervening therapy, this 3-period crossover study will be repeated.

Device: Stimulation-ON Active Control

Interventions

Stimulation-ON DEVICE

Active neurostimulation from the NeuroPace RNS® System triggered by a biomarker

Arm 1: Intervention (stimulation ON)

Stimulation-OFF DEVICE

No neurostimulation from the NeuroPace RNS® System

Arm 2: Sham Control (stimulation OFF)

Stimulation-ON Active Control DEVICE

Active neurostimulation from the NeuroPace RNS® System triggered by a sham biomarker

Arm 3: Active Control (stimulation ON triggered by sham biomarker)

Eligibility Criteria

• Age: 22 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Andrew Krystal: lead

Study Sites (1)

University of California, San Francisco

San Francisco, California, 94143, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Depression

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Behavioral Symptoms; Behavior

Study Officials

• Andrew Krystal, MD, MS

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Katherine Scangos, MD, PhD

CONTACT

415-476-7439; trdepression@ucsf.edu

Rebecca Martinez, MS

CONTACT

415-476-7439; rebecca.martinez@ucsf.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: June 26, 2019
• First Posted: July 1, 2019
• Study Start: July 18, 2019
• Primary Completion (Estimated): June 28, 2030
• Study Completion (Estimated): June 28, 2035
• Last Updated: May 1, 2023

Record last verified: 2023-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)