DBS for TRD With the Medtronic Percept PC

NCT05773755 | Recruiting DMC FDA Device

• 1 other identifier: STUDY-22-01731
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder; Treatment Resistant Depression

Outcome Measures

Primary Outcomes (1)

• 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.

  baseline and up to 1 year

Secondary Outcomes (1)

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

  baseline and up to 1 year

Study Arms (1)

Deep Brain Stimulation (DBS) for Treatment Resistant Depression

EXPERIMENTAL

Open label active Deep Brain Stimulation (DBS)

Device: Medtronic Percept PC DBS system

Interventions

Medtronic Percept PC DBS system DEVICE

Open label active Deep Brain Stimulation (DBS)

Deep Brain Stimulation (DBS) for Treatment Resistant Depression

Eligibility Criteria

• Age: 25 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• ability comply with study and device management procedures.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Helen Mayberg, MD: lead

Study Sites (1)

Icahn School of Medicine at Mount Sinai, Mount Sinai West

New York, New York, 10019, United States

RECRUITING

Related Publications (18)

• 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.

  PMID: 28397839 BACKGROUND

• 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.

  PMID: 31581800 BACKGROUND

• 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.

  PMID: 32418613 BACKGROUND

• 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.

  PMID: 29950982 BACKGROUND

• 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.

  PMID: 30120851 BACKGROUND

• 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.

  PMID: 31314668 BACKGROUND

• Howell B, Choi KS, Gunalan K, Rajendra J, Mayberg HS, McIntyre CC. Quantifying the axonal pathways directly stimulated in therapeutic subcallosal cingulate deep brain stimulation. Hum Brain Mapp. 2019 Feb 15;40(3):889-903. doi: 10.1002/hbm.24419. Epub 2018 Oct 11.

  PMID: 30311317 BACKGROUND

• 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.

  PMID: 36061500 BACKGROUND

• 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.

  PMID: 36288215 BACKGROUND

• Tiruvadi V, Choi KS, Gross RE, Butera R, Jirsa V, Mayberg H. Dynamic Oscillations Evoked by Subcallosal Cingulate Deep Brain Stimulation. Front Neurosci. 2022 Feb 23;16:768355. doi: 10.3389/fnins.2022.768355. eCollection 2022.

  PMID: 35281513 BACKGROUND

• 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.

  PMID: 30441645 BACKGROUND

• 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.

  PMID: 31352356 BACKGROUND

• Harati S, Crowell A, Mayberg H, Nemati S. Addressing the Credit Assignment Problem in Treatment Outcome Prediction using Temporal Difference Learning. Pac Symp Biocomput. 2020;25:43-54.

  PMID: 31797585 BACKGROUND

• Mazza A, Barucchi AM, Solimei GE, Viti M. [Clinical and immunological aspects of Lichen ruber planus]. Arch Stomatol (Napoli). 1988 Oct;29(4):657-66. Italian.

  PMID: 3274606 BACKGROUND

• Riva-Posse P, Holtzheimer PE, Garlow SJ, Mayberg HS. Practical considerations in the development and refinement of subcallosal cingulate white matter deep brain stimulation for treatment-resistant depression. World Neurosurg. 2013 Sep-Oct;80(3-4):S27.e25-34. doi: 10.1016/j.wneu.2012.11.074. Epub 2012 Dec 13.

  PMID: 23246630 BACKGROUND

• Crowell AL, Garlow SJ, Riva-Posse P, Mayberg HS. Characterizing the therapeutic response to deep brain stimulation for treatment-resistant depression: a single center long-term perspective. Front Integr Neurosci. 2015 Jun 15;9:41. doi: 10.3389/fnint.2015.00041. eCollection 2015.

  PMID: 26124710 BACKGROUND

• Riva-Posse P, Choi KS, Holtzheimer PE, McIntyre CC, Gross RE, Chaturvedi A, Crowell AL, Garlow SJ, Rajendra JK, Mayberg HS. Defining critical white matter pathways mediating successful subcallosal cingulate deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2014 Dec 15;76(12):963-9. doi: 10.1016/j.biopsych.2014.03.029. Epub 2014 Apr 13.

  PMID: 24832866 BACKGROUND

• Sendi MSE, Waters AC, Tiruvadi V, Riva-Posse P, Crowell A, Isbaine F, Gale JT, Choi KS, Gross RE, S Mayberg H, Mahmoudi B. Intraoperative neural signals predict rapid antidepressant effects of deep brain stimulation. Transl Psychiatry. 2021 Nov 3;11(1):551. doi: 10.1038/s41398-021-01669-0.

  PMID: 34728599 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Helen Mayberg, MD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Isha Trivedi

CONTACT

212-523-8242; isha.trivedi@mssm.edu

Zoe Schreiber

CONTACT

212-241-6539; zoe.schreiber@mssm.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Masking Details: N/A. This is open label study.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor, Neurology, Neurosurgery, Psychiatry and Neuroscience

Model Details: All participants will be implanted with the study device and receive open label, active DBS stimulation

Study Record Dates

• First Submitted: February 21, 2023
• First Posted: March 17, 2023
• Study Start: March 1, 2023
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ICF
• Time Frame: Beginning 9 months and ending 36 months following article publication.
• 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).

Locations

US (1)