Model-based Electrical Brain Stimulation

Sponsor

University of Southern California (Other)

Overall Status

Recruiting

CT.gov ID

NCT05327387

Collaborator

National Institute of Mental Health (NIMH) (NIH), University of California, San Francisco (Other)

Enrollment

Locations

Arm

49.7

Anticipated Duration (Months)

12.5

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief 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. 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 closed-loop 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.

Condition or Disease	Intervention/Treatment	Phase
Medication Refractory Epilepsy Patients With Electrodes Already Implanted Based on Clinical Criteria for Standard Monitoring	Other: model-based electrical brain stimulation	N/A

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 our 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 decoders that can track these depression symptoms from iEEG activity. The investigators will also apply electrical stimulation to learn a personalized input-output model that predicts the iEEG response to ongoing stimulation. The resulting personalized decoder and the input-output model will be combined to achieve model-based personalization of stimulation therapy.

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

Study Design

Study Type:

Interventional

Anticipated Enrollment :

25 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention 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.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)

Primary Purpose:

Basic Science

Official Title:

Model-based Electrical Brain Stimulation

Actual Study Start Date :

Feb 8, 2022

Anticipated Primary Completion Date :

Mar 31, 2026

Anticipated Study Completion Date :

Mar 31, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: model-based electrical brain stimulation	Other: model-based electrical brain stimulation 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.

Arm

Intervention/Treatment

Experimental: model-based electrical brain stimulation

Other: model-based electrical brain stimulation

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.

Outcome Measures

Primary Outcome Measures

Decoded depression symptom ratings based on neural activity [5-10 days]
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)

Secondary Outcome Measures

Hamilton Depression Rating (HAMD-6) self-reports [5-10 days]
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.
Visual Analog Scale (VAS) self-reports [5-10 days]
Visual Analog Scale (VAS) is a fast self-report validated against the Hamilton scale. It can range from 0 to 300, with 300 corresponding to the worst depression symptom. Self-reports are obtained intermittently from the patient.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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.

Exclusion Criteria:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90089
2	University of California, San Francisco	San Francisco	California	United States	94143

Sponsors and Collaborators

University of Southern California
National Institute of Mental Health (NIMH)
University of California, San Francisco

Investigators

Principal Investigator: Maryam M Shanechi, PhD, University of Southern California

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Maryam Shanechi, Associate Professor of Electrical and Computer Engineering and Biomedical Engineering, University of Southern California

ClinicalTrials.gov Identifier:

NCT05327387

Other Study ID Numbers:

HS-21-00108
R01MH123770
DP2MH126378

First Posted:

Apr 14, 2022

Last Update Posted:

Apr 14, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Keywords provided by Maryam Shanechi, Associate Professor of Electrical and Computer Engineering and Biomedical Engineering, University of Southern California

deep brain stimulation

model-based stimulation

closed-loop stimulation

neural biomarkers of depression

neurotechnology

neuropsychiatric disorders

depression

brain-machine interface

Additional relevant MeSH terms:

Drug Resistant Epilepsy

Study Results

No Results Posted as of Apr 14, 2022