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Model-based Electrical Brain Stimulation

Primary Purpose

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

Status

Recruiting

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

model-based electrical brain stimulation

About this trial

This is an interventional basic science trial for Medication Refractory Epilepsy Patients With Electrodes Already Implanted Based on Clinical Criteria for Standard Monitoring focused on measuring deep brain stimulation, model-based stimulation, closed-loop stimulation, neural biomarkers of depression, neurotechnology, neuropsychiatric disorders, depression, brain-machine interface

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

University of Southern CaliforniaRecruiting
University of California, San FranciscoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

model-based electrical brain stimulation

Arm Description

Outcomes

Primary Outcome Measures

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)

Secondary Outcome Measures

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.

Visual Analog Scale (VAS) self-reports

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.

Full Information

NCT ID

NCT05327387

First Posted

March 24, 2022

Last Updated

April 6, 2022

Sponsor

University of Southern California

Collaborators

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

1. Study Identification

Unique Protocol Identification Number

NCT05327387

Brief Title

Model-based Electrical Brain Stimulation

Official Title

Model-based Electrical Brain Stimulation

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Recruiting

Study Start Date

February 8, 2022 (Actual)

Primary Completion Date

March 31, 2026 (Anticipated)

Study Completion Date

March 31, 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

University of Southern California

Collaborators

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

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

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

Keywords

deep brain stimulation, model-based stimulation, closed-loop stimulation, neural biomarkers of depression, neurotechnology, neuropsychiatric disorders, depression, brain-machine interface

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Single Group Assignment

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)

Allocation

N/A

Enrollment

25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

model-based electrical brain stimulation

Arm Type

Experimental

Intervention Type

Other

Intervention Name(s)

model-based electrical brain stimulation

Intervention Description

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.

Primary Outcome Measure Information:

Title

Decoded depression symptom ratings based on neural activity

Description

Time Frame

5-10 days

Secondary Outcome Measure Information:

Title

Hamilton Depression Rating (HAMD-6) self-reports

Description

Time Frame

5-10 days

Title

Visual Analog Scale (VAS) self-reports

Description

Time Frame

5-10 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Maryam M Shanechi, PhD

Phone

213-740-1377

shanechi@usc.edu

First Name & Middle Initial & Last Name or Official Title & Degree

Omid G Sani, PhD

Phone

213-740-1377

ghasemsa@usc.edu

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Maryam M Shanechi, PhD

Organizational Affiliation

University of Southern California

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Southern California

City

Los Angeles

State/Province

California

ZIP/Postal Code

90089

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Maryam Shanechi, PhD

Phone

213-740-1377

shanechi@usc.edu

First Name & Middle Initial & Last Name & Degree

Maryam M Shanechi, PhD

Facility Name

University of California, San Francisco

City

San Francisco

State/Province

California

ZIP/Postal Code

94143

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Edward F Chang, MD

Phone

415-502-7346

edward.chang@ucsf.edu

First Name & Middle Initial & Last Name & Degree

Edward F Chang, MD

12. IPD Sharing Statement

Plan to Share IPD

Yes

IPD Sharing Plan Description

Upon completion of the study and after publication, fully de-identified IPD can be made available for research purposes.

IPD Sharing Time Frame

The sharing will happen upon completion of the study and after publication.

IPD Sharing Access Criteria

Data will be accessed through data publishing platforms such as the NIH/NIMH Data Archive (NDA).

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Model-based Electrical Brain Stimulation

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