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Medication Refractory Epilepsy Patients With Electrodes Already Implanted Based on Clinical Criteria for Standard MonitoringNCT05327387

Model-based Electrical Brain Stimulation

A study testing model-based electrical brain stimulation in people with Medication Refractory Epilepsy Patients With Electrodes Already Implanted Based on Clinical Criteria for Standard Monitoring, run by University of Southern California at 2 sites in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial summary

Neuropsychiatric disorders are a leading cause of disability worldwide with depressive disorders being one of the most disabling among them. Also, millions of patients do not respond to current medications or psychotherapy, which makes it critical to find an alternative therapy. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
model-based electrical brain stimulation
Could I receive a placebo?
No, everyone receives an active treatment
How many people
25 participants
Where
2 sitesUnited States
Study dates
8 Feb 2022to 31 Mar 2026
Phase
Interventional
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patients being evaluated for surgical treatment of medication refractory epilepsy and brain tumors will be studied. ONLY patients with electrodes implanted based on clinical criteria to locate their seizure focus will be studied. Most patients are healthy adults, outside of their epilepsy and/or brain tumor.
  • Subjects >= 18 are only included in this study.
  • All patients with the above conditions and with implanted electrode arrays who are willing to participate and able to cooperate and follow research instructions will be recruited. However, analysis of research recording data will focus on those subjects with an IQ >= 80, with no impairments of reading, naming, or articulation (to minimize confounds such as abnormal language processing that may affect their self-reporting with the questionnaire), and with no cerebral pathology affecting the cortical regions from which recordings are made.

Who cannot join

  • Subjects < 18 years old will be excluded from this study due to the high concordance of developmental disorders (cognitive and language-related) in pediatric epilepsies.
  • There will be no involvement of special classes of subjects, such as fetuses, neonates, pregnant women, children, prisoners, institutionalized individuals, or others who may be considered vulnerable populations.
  • Patients who are unable to give informed consent due to a brain disorder will be excluded from the study, as it is very likely that they would be unable to carry out the tasks demanded by the study.

Trial locations and contacts

2 sites in 1 country. Contact the study team or a site near you to ask about taking part.

Maryam M Shanechi, PhD contact

213-740-1377

shanechi@usc.edu

HyeongChan Jo, PhD contact

hj_380@usc.edu

United States2 sites, 2 recruiting
  • University of Southern California

    Los Angeles, California, 90089

    Maryam Shanechi, PhD, 213-740-1377, shanechi@usc.edu

    Maryam M Shanechi, PhD

    Recruiting
  • University of California, San Francisco

    San Francisco, California, 94143

    Edward F Chang, MD, 415-502-7346, edward.chang@ucsf.edu

    Edward F Chang, MD

    Recruiting

Other trials in United States

About this study

Neuropsychiatric disorders are a leading cause of disability worldwide with depressive disorders being one of the most disabling among them. Also, millions of patients do not respond to current medications or psychotherapy, which makes it critical to find an alternative therapy. Applying electrical stimulation at various brain targets has shown promise but there is a critical need to improve efficacy.

Given inter- and intra-subject variabilities in neuropsychiatric disorders, this study aims to enable personalizing the stimulation therapy via i) tracking a patient's own symptoms based on their neural activity, and ii) a model of how their neural activity responds to stimulation therapy. The study will develop the modeling elements needed to realize a model-based personalized system for electrical brain stimulation to achieve this aim.

The study will provide proof-of-concept demonstration in epilepsy patients who already have intracranial electroencephalography (iEEG) electrodes implanted for their standard clinical monitoring unrelated to this study, and who consent to being part of the study.

Read the detailed description

The investigators will conduct the study for each subject during their stay in the epilepsy monitoring unit (EMU), which is dictated purely based on their standard clinical needs unrelated to this study. iEEG will be recorded from each patient throughout their stay in the EMU, during which the self-reports from them will be also intermittently collected using validated questionnaires that relate to depression symptoms.

The investigators will build subject-specific decoders that can track these depression symptoms from iEEG activity. The investigators will also apply electrical stimulation to learn a subject-specific input-output model that predicts the iEEG response to ongoing stimulation.

Successful completion of this study will help enable precisely-tailored deep brain stimulation therapies across diverse conditions and have a broad public health impact.

Being tested
model-based electrical brain stimulation
Keywords
deep brain stimulation, model-based stimulation, neural biomarkers of depression, neurotechnology, neuropsychiatric disorders, depression, brain-machine interface
Medical subject headings
Depression

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • model-based electrical brain stimulationOther

    Electrical pulse train stimulation delivered to medication refractory epilepsy patients with electrodes already implanted based on clinical criteria for standard monitoring unrelated to this study. The delivery of the electrical brain stimulation can be guided by neural biomarkers of symptom levels computed from ongoing neural activity and by input-output models of neural response to stimulation therapy. The parameters of electrical stimulation will be constrained to be within clinically safe ranges.

Study groups in NCT05327387
Study groupRoleWhat they receive
model-based electrical brain stimulationExperimentalNot described
Receives: Other: model-based electrical brain stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Decoded depression symptom ratings based on neural activity

    A personalized decoder is trained for each patient using the recorded neural activity and self-reports. Then this decoder is used to estimate the biomarker purely from neural activity; that is, based on neural activity, it will return the estimation of depression symptom ratings (HAMD-6 or VAS self-reports)

    Measured: 5-10 days

Secondary outcomes (2)
  1. Hamilton Depression Rating (HAMD-6) self-reports

    Hamilton Depression Rating (HAMD-6) is a widely used questionnaire that measures depressive state severity and intervention response. It can range from 0 to 22, with 22 corresponding to the worst depression symptom. Self-reports are obtained intermittently from the patient.

    Measured: 5-10 days

  2. Visual Analog Scale (VAS) self-reports

    Visual Analog Scale (VAS) is a fast self-report validated against the Hamilton scale. It indicates the symptom level along a continuous line from none to worst symptom level. Self-reports are obtained intermittently from the patient.

    Measured: 5-10 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted14 Apr 2022
  2. Study start8 Feb 2022
  3. Primary completion31 Mar 2026 (estimated)
  4. Study completion31 Mar 2026 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Basic science
Allocation
Not applicable
Intervention model
Single group
Model description
In each patient, the investigators will test the decoders of the symptom level and the input-output models of the neural response to stimulation therapy.
Masking
None (open label)
Enrolment
25 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05327387
Sponsor's protocol ID
HS-21-00108
Other IDs
R01MH123770, DP2MH126378, R61MH135407
Status last verified
Jun 2025
First submitted
24 Mar 2022
Last updated
22 Sep 2025
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Upon completion of the study and after publication, fully de-identified IPD can be made available for research purposes.

Publications

  • Whiteford HA, Degenhardt L, Rehm J, Baxter AJ, Ferrari AJ, Erskine HE, Charlson FJ, Norman RE, Flaxman AD, Johns N, Burstein R, Murray CJ, Vos T. Global burden of disease attributable to mental and substance use disorders: findings from the Global Burden of Disease Study 2010. Lancet. 2013 Nov 9;382(9904):1575-86. doi: 10.1016/S0140-6736(13)61611-6. Epub 2013 Aug 29.

    PubMed 23993280
  • Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.

    PubMed 17074942
  • Mayberg HS, Lozano AM, Voon V, McNeely HE, Seminowicz D, Hamani C, Schwalb JM, Kennedy SH. Deep brain stimulation for treatment-resistant depression. Neuron. 2005 Mar 3;45(5):651-60. doi: 10.1016/j.neuron.2005.02.014.

    PubMed 15748841
  • Lozano AM, Mayberg HS, Giacobbe P, Hamani C, Craddock RC, Kennedy SH. Subcallosal cingulate gyrus deep brain stimulation for treatment-resistant depression. Biol Psychiatry. 2008 Sep 15;64(6):461-7. doi: 10.1016/j.biopsych.2008.05.034. Epub 2008 Jul 18.

    PubMed 18639234
  • Schlaepfer TE, Cohen MX, Frick C, Kosel M, Brodesser D, Axmacher N, Joe AY, Kreft M, Lenartz D, Sturm V. Deep brain stimulation to reward circuitry alleviates anhedonia in refractory major depression. Neuropsychopharmacology. 2008 Jan;33(2):368-77. doi: 10.1038/sj.npp.1301408. Epub 2007 Apr 11.

    PubMed 17429407
  • Malone DA Jr, Dougherty DD, Rezai AR, Carpenter LL, Friehs GM, Eskandar EN, Rauch SL, Rasmussen SA, Machado AG, Kubu CS, Tyrka AR, Price LH, Stypulkowski PH, Giftakis JE, Rise MT, Malloy PF, Salloway SP, Greenberg BD. Deep brain stimulation of the ventral capsule/ventral striatum for treatment-resistant depression. Biol Psychiatry. 2009 Feb 15;65(4):267-75. doi: 10.1016/j.biopsych.2008.08.029. Epub 2008 Oct 8.

    PubMed 18842257
  • Bewernick BH, Kayser S, Sturm V, Schlaepfer TE. Long-term effects of nucleus accumbens deep brain stimulation in treatment-resistant depression: evidence for sustained efficacy. Neuropsychopharmacology. 2012 Aug;37(9):1975-85. doi: 10.1038/npp.2012.44. Epub 2012 Apr 4.

    PubMed 22473055
  • Holtzheimer PE, Kelley ME, Gross RE, Filkowski MM, Garlow SJ, Barrocas A, Wint D, Craighead MC, Kozarsky J, Chismar R, Moreines JL, Mewes K, Posse PR, Gutman DA, Mayberg HS. Subcallosal cingulate deep brain stimulation for treatment-resistant unipolar and bipolar depression. Arch Gen Psychiatry. 2012 Feb;69(2):150-8. doi: 10.1001/archgenpsychiatry.2011.1456. Epub 2012 Jan 2.

    PubMed 22213770
  • Schlaepfer TE, Bewernick BH, Kayser S, Madler B, Coenen VA. Rapid effects of deep brain stimulation for treatment-resistant major depression. Biol Psychiatry. 2013 Jun 15;73(12):1204-12. doi: 10.1016/j.biopsych.2013.01.034. Epub 2013 Apr 3.

    PubMed 23562618
  • Dougherty DD, Rezai AR, Carpenter LL, Howland RH, Bhati MT, O'Reardon JP, Eskandar EN, Baltuch GH, Machado AD, Kondziolka D, Cusin C, Evans KC, Price LH, Jacobs K, Pandya M, Denko T, Tyrka AR, Brelje T, Deckersbach T, Kubu C, Malone DA Jr. A Randomized Sham-Controlled Trial of Deep Brain Stimulation of the Ventral Capsule/Ventral Striatum for Chronic Treatment-Resistant Depression. Biol Psychiatry. 2015 Aug 15;78(4):240-8. doi: 10.1016/j.biopsych.2014.11.023. Epub 2014 Dec 13.

    PubMed 25726497
  • Holtzheimer PE, Husain MM, Lisanby SH, Taylor SF, Whitworth LA, McClintock S, Slavin KV, Berman J, McKhann GM, Patil PG, Rittberg BR, Abosch A, Pandurangi AK, Holloway KL, Lam RW, Honey CR, Neimat JS, Henderson JM, DeBattista C, Rothschild AJ, Pilitsis JG, Espinoza RT, Petrides G, Mogilner AY, Matthews K, Peichel D, Gross RE, Hamani C, Lozano AM, Mayberg HS. Subcallosal cingulate deep brain stimulation for treatment-resistant depression: a multisite, randomised, sham-controlled trial. Lancet Psychiatry. 2017 Nov;4(11):839-849. doi: 10.1016/S2215-0366(17)30371-1. Epub 2017 Oct 4.

    PubMed 28988904
  • Dandekar MP, Fenoy AJ, Carvalho AF, Soares JC, Quevedo J. Deep brain stimulation for treatment-resistant depression: an integrative review of preclinical and clinical findings and translational implications. Mol Psychiatry. 2018 May;23(5):1094-1112. doi: 10.1038/mp.2018.2. Epub 2018 Feb 27.

    PubMed 29483673
  • Bergfeld IO, Mantione M, Hoogendoorn ML, Ruhe HG, Notten P, van Laarhoven J, Visser I, Figee M, de Kwaasteniet BP, Horst F, Schene AH, van den Munckhof P, Beute G, Schuurman R, Denys D. Deep Brain Stimulation of the Ventral Anterior Limb of the Internal Capsule for Treatment-Resistant Depression: A Randomized Clinical Trial. JAMA Psychiatry. 2016 May 1;73(5):456-64. doi: 10.1001/jamapsychiatry.2016.0152.

    PubMed 27049915
  • Kennedy SH, Giacobbe P, Rizvi SJ, Placenza FM, Nishikawa Y, Mayberg HS, Lozano AM. Deep brain stimulation for treatment-resistant depression: follow-up after 3 to 6 years. Am J Psychiatry. 2011 May;168(5):502-10. doi: 10.1176/appi.ajp.2010.10081187. Epub 2011 Feb 1.

    PubMed 21285143
  • Blomstedt P, Naesstrom M, Bodlund O. Deep brain stimulation in the bed nucleus of the stria terminalis and medial forebrain bundle in a patient with major depressive disorder and anorexia nervosa. Clin Case Rep. 2017 Mar 31;5(5):679-684. doi: 10.1002/ccr3.856. eCollection 2017 May.

    PubMed 28469875

Questions about this trial

What is this clinical trial studying?

A study testing model-based electrical brain stimulation in people with Medication Refractory Epilepsy Patients With Electrodes Already Implanted Based on Clinical Criteria for Standard Monitoring, run by University of Southern California at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 22 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Maryam M Shanechi, PhD (213-740-1377, shanechi@usc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Decoded depression symptom ratings based on neural activity (time frame: 5-10 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05327387, which also lists 28 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Sep 2025.

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