DBS for TRD With the Medtronic Percept PC

Major Depressive Disorder Clinical Trial

Official title:

Deep Brain Stimulation for Treatment Resistant Depression: Exploration of Local Field Potentials (LFPs) With the Medtronic Percept PC System

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05773755
• Other study ID #: STUDY-22-01731
• Status: Recruiting
• Phase: N/A
• Start date: March 1, 2023
• Est. completion date: December 2028

Study information

• Verified date: October 2023
• Source: Icahn School of Medicine at Mount Sinai
• Contact: Isha Trivedi
• Phone: 212-523-8242
• Email: isha.trivedi[@]mssm.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 10
• Est. completion date: December 2028
• Est. primary completion date: December 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major
• Depressive Disorder, Treatment-Resistant
• Major Depressive Disorder
• Treatment Resistant Depression

Intervention

Device:
• Medtronic Percept PC DBS system
Open label active Deep Brain Stimulation (DBS)

Locations

Country	Name	City	State
United States	Icahn School of Medicine at Mount Sinai, Mount Sinai West	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Helen Mayberg, MD

Country where clinical trial is conducted

United States, 

References & Publications (18)

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. — View 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. — View 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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View 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. — View Citation

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. — View 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. — View Citation

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. — View Citation

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. — View 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. — View 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. — View Citation

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. — View 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. — View 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. — View 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. — View Citation

* Note: There are 18 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	baseline and up to 1 year

External Links

•   Icahn School of Medicine at Mount Sinai
•   Nash Family Center for Advanced Circuit Therapeutics, Icahn School of Medicine at Mount Sinai