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DBS for TRD With the Medtronic Percept PC

Primary Purpose

Major Depressive Disorder, Treatment Resistant Depression

Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Medtronic Percept PC DBS system
Sponsored by
Helen Mayberg, MD
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Major Depressive Disorder

Eligibility Criteria

25 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Icahn School of Medicine at Mount Sinai, Mount Sinai WestRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Deep Brain Stimulation (DBS) for Treatment Resistant Depression

Arm Description

Open label active Deep Brain Stimulation (DBS)

Outcomes

Primary Outcome Measures

Change in Hamilton Depression Rating Scale (HDRS) score
Response to intervention defined as a decrease in the HDRS-17 score of 50% or greater from the 4-week average pre-surgical baseline. Clinical remission will be defined as an HDRS-17 score ≤ 7. Partial response will be defined as a decrease in HDRS-17 >30% but less than 50%. Non-response will be defined as a <30% decrease in HDRS-17. The score for Hamilton Depression Rating Scale, 17 item version, ranges from 0-50, with a higher score indicating more severe depression.

Secondary Outcome Measures

Change in Montgomery-Asberg Depression Rating Scale (MADRS)
The MADRS consists of 10 items evaluating core symptoms of depression. Nine of the items are based upon patient report, and one is on the rater's observation during the rating interview. MADRS items are rated on a 0 to 6 continuum (0 = no abnormality, 6 = severe). Scores range from 0 to 60, with higher total scores indicating increased severity of depressive symptoms

Full Information

First Posted
February 21, 2023
Last Updated
October 11, 2023
Sponsor
Helen Mayberg, MD
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1. Study Identification

Unique Protocol Identification Number
NCT05773755
Brief Title
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

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
March 1, 2023 (Actual)
Primary Completion Date
December 2028 (Anticipated)
Study Completion Date
December 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Helen Mayberg, MD

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Treatment Resistant Depression

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
All participants will be implanted with the study device and receive open label, active DBS stimulation
Masking
None (Open Label)
Masking Description
N/A. This is open label study.
Allocation
N/A
Enrollment
10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Deep Brain Stimulation (DBS) for Treatment Resistant Depression
Arm Type
Experimental
Arm Description
Open label active Deep Brain Stimulation (DBS)
Intervention Type
Device
Intervention Name(s)
Medtronic Percept PC DBS system
Intervention Description
Open label active Deep Brain Stimulation (DBS)
Primary Outcome Measure Information:
Title
Change in Hamilton Depression Rating Scale (HDRS) score
Description
Response to intervention defined as a decrease in the HDRS-17 score of 50% or greater from the 4-week average pre-surgical baseline. Clinical remission will be defined as an HDRS-17 score ≤ 7. Partial response will be defined as a decrease in HDRS-17 >30% but less than 50%. Non-response will be defined as a <30% decrease in HDRS-17. The score for Hamilton Depression Rating Scale, 17 item version, ranges from 0-50, with a higher score indicating more severe depression.
Time Frame
baseline and up to 1 year
Secondary Outcome Measure Information:
Title
Change in Montgomery-Asberg Depression Rating Scale (MADRS)
Description
The MADRS consists of 10 items evaluating core symptoms of depression. Nine of the items are based upon patient report, and one is on the rater's observation during the rating interview. MADRS items are rated on a 0 to 6 continuum (0 = no abnormality, 6 = severe). Scores range from 0 to 60, with higher total scores indicating increased severity of depressive symptoms
Time Frame
baseline and up to 1 year

10. Eligibility

Sex
All
Minimum Age & Unit of Time
25 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Isha Trivedi
Phone
212-523-8242
Email
isha.trivedi@mssm.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Zoe Schreiber
Phone
212-241-6539
Email
zoe.schreiber@mssm.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Helen Mayberg, MD
Organizational Affiliation
Icahn School of Medicine at Mount Sinai
Official's Role
Principal Investigator
Facility Information:
Facility Name
Icahn School of Medicine at Mount Sinai, Mount Sinai West
City
New York
State/Province
New York
ZIP/Postal Code
10019
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Isha Trivedi
Phone
212-523-8242
Email
isha.trivedi@mssm.edu

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures, and appendices).
IPD Sharing Time Frame
Beginning 9 months and ending 36 months following article publication.
IPD Sharing Access Criteria
Investigators whose proposed use of the data has been approved by an independent review committee ('learned intermediary') identified for this purpose. For individual participant data meta-analysis. Proposals should be directed to helen.mayberg@mssm.edu. To gain access, data requestors will need to sign a data access agreement. Data are available for 5 years at a third party website (Link to be included in the URL field below).
Citations:
PubMed Identifier
28397839
Citation
Riva-Posse P, Choi KS, Holtzheimer PE, Crowell AL, Garlow SJ, Rajendra JK, McIntyre CC, Gross RE, Mayberg HS. A connectomic approach for subcallosal cingulate deep brain stimulation surgery: prospective targeting in treatment-resistant depression. Mol Psychiatry. 2018 Apr;23(4):843-849. doi: 10.1038/mp.2017.59. Epub 2017 Apr 11.
Results Reference
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PubMed Identifier
31581800
Citation
Crowell AL, Riva-Posse P, Holtzheimer PE, Garlow SJ, Kelley ME, Gross RE, Denison L, Quinn S, Mayberg HS. Long-Term Outcomes of Subcallosal Cingulate Deep Brain Stimulation for Treatment-Resistant Depression. Am J Psychiatry. 2019 Nov 1;176(11):949-956. doi: 10.1176/appi.ajp.2019.18121427. Epub 2019 Oct 4.
Results Reference
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PubMed Identifier
32418613
Citation
Riva-Posse P, Crowell AL, Wright K, Waters AC, Choi K, Garlow SJ, Holtzheimer PE, Gross RE, Mayberg HS. Rapid Antidepressant Effects of Deep Brain Stimulation and Their Relation to Surgical Protocol. Biol Psychiatry. 2020 Oct 15;88(8):e37-e39. doi: 10.1016/j.biopsych.2020.03.017. Epub 2020 May 14. No abstract available.
Results Reference
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PubMed Identifier
29950982
Citation
Smart O, Choi KS, Riva-Posse P, Tiruvadi V, Rajendra J, Waters AC, Crowell AL, Edwards J, Gross RE, Mayberg HS. Initial Unilateral Exposure to Deep Brain Stimulation in Treatment-Resistant Depression Patients Alters Spectral Power in the Subcallosal Cingulate. Front Comput Neurosci. 2018 Jun 12;12:43. doi: 10.3389/fncom.2018.00043. eCollection 2018.
Results Reference
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PubMed Identifier
30120851
Citation
Waters AC, Veerakumar A, Choi KS, Howell B, Tiruvadi V, Bijanki KR, Crowell A, Riva-Posse P, Mayberg HS. Test-retest reliability of a stimulation-locked evoked response to deep brain stimulation in subcallosal cingulate for treatment resistant depression. Hum Brain Mapp. 2018 Dec;39(12):4844-4856. doi: 10.1002/hbm.24327. Epub 2018 Aug 18.
Results Reference
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PubMed Identifier
31314668
Citation
Veerakumar A, Tiruvadi V, Howell B, Waters AC, Crowell AL, Voytek B, Riva-Posse P, Denison L, Rajendra JK, Edwards JA, Bijanki KR, Choi KS, Mayberg HS. Field potential 1/f activity in the subcallosal cingulate region as a candidate signal for monitoring deep brain stimulation for treatment-resistant depression. J Neurophysiol. 2019 Sep 1;122(3):1023-1035. doi: 10.1152/jn.00875.2018. Epub 2019 Jul 17.
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PubMed Identifier
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Citation
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Results Reference
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PubMed Identifier
36061500
Citation
Smith EE, Choi KS, Veerakumar A, Obatusin M, Howell B, Smith AH, Tiruvadi V, Crowell AL, Riva-Posse P, Alagapan S, Rozell CJ, Mayberg HS, Waters AC. Time-frequency signatures evoked by single-pulse deep brain stimulation to the subcallosal cingulate. Front Hum Neurosci. 2022 Aug 18;16:939258. doi: 10.3389/fnhum.2022.939258. eCollection 2022.
Results Reference
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PubMed Identifier
36288215
Citation
Tiruvadi V, James S, Howell B, Obatusin M, Crowell A, Riva-Posse P, Gross RE, McIntyre CC, Mayberg HS, Butera R. Mitigating Mismatch Compression in Differential Local Field Potentials. IEEE Trans Neural Syst Rehabil Eng. 2023;31:68-77. doi: 10.1109/TNSRE.2022.3217469. Epub 2023 Jan 30.
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PubMed Identifier
35281513
Citation
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Results Reference
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PubMed Identifier
30441645
Citation
Harati S, Crowell A, Mayberg H, Nemati S. Depression Severity Classification from Speech Emotion. Annu Int Conf IEEE Eng Med Biol Soc. 2018 Jul;2018:5763-5766. doi: 10.1109/EMBC.2018.8513610.
Results Reference
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PubMed Identifier
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Citation
Harati S, Crowell A, Huang Y, Mayberg H, Nemati S. Classifying Depression Severity in Recovery From Major Depressive Disorder via Dynamic Facial Features. IEEE J Biomed Health Inform. 2020 Mar;24(3):815-824. doi: 10.1109/JBHI.2019.2930604. Epub 2019 Jul 23.
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PubMed Identifier
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Citation
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Links:
URL
https://icahn.mssm.edu/research/advanced-circuit-therapeutics
Description
Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai
URL
https://icahn.mssm.edu/
Description
Icahn School of Medicine at Mount Sinai

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DBS for TRD With the Medtronic Percept PC

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