Clinical trial NCT05773755: DBS for TRD with the Medtronic Percept PC
Official title: Deep Brain Stimulation for Treatment Resistant Depression: Exploration of Local Field Potentials (LFPs) with the Medtronic Percept PC System
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Major Depressive Disorder
Treatment Resistant Depression
Lead sponsor: Icahn School of Medicine at Mount Sinai
Sponsor class: OTHER
First posted: 2023-03-17
Enrollment: 10
Sex: ALL
Minimum age (years): 25
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: All participants will be implanted with the study device and receive open label, active DBS stimulation
Primary purpose: BASIC_SCIENCE

Brief summary: Of the estimated 30 million Americans who suffer from Major Depressive Disorder, approximately 10% are considered treatment resistant. Deep brain stimulation (DBS) to a region of the brain called the subcallosal cingulate (SCC) is an emerging strategy for treatment resistant depression (TRD), which involves placement of electrodes in a specific region of the brain and stimulating that area with electricity. This is believed to reset the brain network responsible for symptoms and results in a significant antidepressant response. A series of open-label studies have demonstrated sustained, long-term antidepressant effects in 40-60% of patients who received this treatment. A challenge to the effective dissemination of this fledgling treatment is the absence of biomarkers (objective, measureable indications of the state of the body and brain) to guide device placement and select stimulation parameters during follow-up care.

By using a DBS device called the Percept PC (Medtronic, Inc) which has the ability to both deliver stimulation to and record electrical signals directly from the brain, this study aims to identify changes in local field potentials (LFPs), specific electrical signals that are thought to represent how the brain communicates information from one region to another, to see how this relates to DBS parameter settings and patient depressive symptomatology. The goal of this study is to study LFPs before and during active DBS stimulation to identify changes that correlate with the antidepressant effects of SCC DBS.

The study team will recruit 10 patients with TRD and implant them with the Percept PC system. Participants will be asked to complete short questionnaires and collect LFP data twice daily for the first year of the study, as well as have weekly in person research procedures and assessments with the study team for up to one year. These include meetings with the study psychiatrist, psychologist, symptom ratings, and movement, voice, and video recordings. A brief discontinuation experiment will be conducted after 6 months of stimulation, in which the stimulation will be turned off and patterns of LFP changes will be recorded. The entire study is expected to last about 5 years, parcellated into several study phases. All participants are required to live in the New York metropolitan area for the first several months of the study.


Eligibility criteria: Inclusion Criteria:

* Age 25-70 years old.
* Ability to provide written informed consent.
* Primary psychiatric diagnosis of Major Depressive Disorder (MDD), either single episode or recurrent type, without psychotic features, currently experiencing a Major Depressive Episode (MDE), as diagnosed by Structured Clinical Interview for DSM IV-TR or DSM-5 (SCID-IV or SCID-5). Two independent psychiatrists will confirm the diagnosis, as well.
* Current depressive episode of at least two years duration OR a history of more than 3 lifetime depressive episodes.
* Minimum score at study entry of 20 on the 17-item Hamilton Depression Rating Scale
* Average pre-operative HDRS-17 score of 20 or greater (averaged over four weekly pre-surgical evaluations during the four weeks prior to surgery)
* A maximum Global Assessment of Functioning of 50 or less.
* Confirmed to have treatment-resistant depression (TRD). Treatment-resistance will be defined as failure to respond to at least four adequate antidepressant treatments (assessed with the Antidepressant Treatment History Form \[ATHF-SF\] and verified through medical records) during the current episode. Treatments which support study inclusion include antidepressive medications, certain augmentation agents, evidenced-based psychotherapy, and neuromodulation (ECT, transcranial magnetic stimulation (TMS)). For those patients who have not received ECT, patients may be considered eligible for study participation if they have received adequate trials of an SSRI, SNRI, augmentation agent (certain atypical antipsychotic medications, Lithium), and TMS and/or ketamine.
* ability comply with study and device management procedures.

Exclusion criteria:

* Other primary Axis I conditions
* Active suicidal ideation with intent, suicide attempt within the last six months, more than three suicide attempts within the last two years, or serious suicide risk as determined by the study psychiatrists
* Other primary neurological disorders or unstable medical illness
* Conditions requiring anticoagulant therapy which cannot be discontinued for the perioperative period, as required
* Pregnancy or plan to come pregnant during the study
* Contraindications for general anesthesia, neurosurgery, or an MRI scan
* Currently implanted with a cardiac pacemaker / defibrillator or other implanted electrical device which may interfere with DBS stimulator or the function of which may be impacted by its implantation.

Primary outcomes:
measure: Change in Hamilton Depression Rating Scale (HDRS) score
timeFrame: baseline and up to 1 year
Secondary outcomes:
measure: Change in Montgomery-Asberg Depression Rating Scale (MADRS)
timeFrame: baseline and up to 1 year
Other outcomes:
Locations:
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai, Mount Sinai West
state: New York
Study officials:
affiliation: Icahn School of Medicine at Mount Sinai
name: Helen Mayberg, MD
role: PRINCIPAL_INVESTIGATOR
References:
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