Transcranial Electric Stimulation Therapy (TEST) for Treatment Resistant Depression (TRD

Sponsor

National Institute of Mental Health (NIMH) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT05172271

Collaborator

(none)

Enrollment

Location

Arms

34.8

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Background:

People with TRD are often helped by electroconvulsive therapy (ECT). But ECT can affect memory and thinking. Researchers want to study a treatment called TEST that uses less electricity.

Objective:

To study the safety and feasibility of TEST and assess its antidepressant effects.

Eligibility:

Adults aged 25-64 with major depression that has not been relieved by current treatments.

Design:

Participants will be admitted to the NIH Clinical Center for 5 18 weeks over 2 3 treatment phases. Their medications may be adjusted.

Participants will be interviewed about their depression, side effects, and other treatments they are receiving. They will complete questionnaires. They will give blood and urine samples. Their brain waves and heart rhythm will be recorded. They will take tests of memory, attention, mental functioning, and thinking.

Participants will have magnetic resonance imaging (MRI) scans of the head and brain. They will lie on a table that slides in and out of the scanner. Pictures of brain chemicals will also be taken. They may complete tasks during the MRI.

Participants will receive TEST and/or sham treatments. They may receive optional ECT. An intravenous catheter will be placed in an arm vein to receive general anesthesia. Two electrodes will be placed on the front of their head. An electric current will be passed from the ECT machine through the electrodes. For sham treatments, they will not receive the electric current. Their breathing, heart rate, brain function, blood pressure, and body movements will be measured.

Participants will have 7 follow-up visits over 6 months. Visits can be done via telehealth.

Participation will last for up to 42 weeks.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder Bipolar Disorder Unipolar Major Depression	Device: MagPro TMS Stimulator and coil Device: Thymatron System IV Device: Magnetic Resonance Imaging Scanner Other: ECT device without stimulation	N/A

Detailed Description

Study Description:

This is a medical device feasibility study, which per FDA definition, is a study focusing primarily on continuing safety data collection that aims to capture preliminary safety and effectiveness data on a near-final or final device design to adequately plan an appropriate pivotal study. It tests the hypothesis that Transcranial Electric Stimulation Therapy (TEST), an experimental brain stimulation therapy, can have an antidepressant effect in individuals with treatment resistant depression (TRD) safely and without significant adverse cognitive effects. TEST involves bifrontal electrical brain stimulation at a dose below the seizure threshold, applied in the same manner as standard electroconvulsive therapy (ECT), with scalp electrodes, under anesthesia, using a standard ECT device. The effects of TEST will be compared to those of sham TEST (anesthesia alone) in 30 inpatients with TRD in a randomized, double-blind, parallel trial, followed by a nonrandomized extension during which all participants are eligible for active treatment.

Objectives:

Primary Objective: To evaluate the safety and feasibility of TEST in 30 adults with treatment resistant major depression (TRD)

Secondary Objectives: To assess the antidepressant effect of TEST.

Endpoints: Primary Endpoints: 1.Treatment adverse effects with an emphasis on adverse cognitive effects, primarily memory impairment. 2.Presence or absence of a seizure in participants receiving TEST (feasibility of consistently not inducing seizures with TEST)

Secondary Endpoint: Treatment-related changes in depressive symptom scale score

Study Design

Study Type:

Interventional

Anticipated Enrollment :

35 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Device Feasibility

Official Title:

A Feasibility Study of Transcranial Electric Stimulation Therapy (TEST) for Treatment Resistant Depression (TRD)

Anticipated Study Start Date :

Aug 30, 2022

Anticipated Primary Completion Date :

Jul 23, 2025

Anticipated Study Completion Date :

Jul 23, 2025

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: Sham TEST Anesthesia alone	Other: ECT device without stimulation Anesthesia alone
Experimental: Transcranial Electric Stimulation Therapy (TEST) TEST involves bifrontal electrical brain stimulation at a dose below the seizure threshold, applied in the same manner as standard electroconvulsive therapy (ECT), with scalp electrodes, under anesthesia, using a standard ECT device (modified or unmodified) that can deliver a range of doses below seizure threshold.	Device: MagPro TMS Stimulator and coil TMS measurements of cortical excitability pre and post study intervention Device: Thymatron System IV The Thymatron System IV (Somatics LLC, Venice, FL, USA)is an FDA 510(k)-cleared ECT device. For TESt, we will be using it in a non FDA-approved manner--stimulating without intending to induce seizures. Device: Magnetic Resonance Imaging Scanner Conventional MRI studies in this protocol are considered non-significant risk (NSR) devices. While operated in research mode, the MRI will be under the International Electrotechnical Commission (IEC) 60601-2-33 First Level Controlled Operating Mode, which allows for research pulse sequences to be used within the FDA/IEC safety limits for MRI devices.

Arm

Intervention/Treatment

Sham Comparator: Sham TEST

Anesthesia alone

Other: ECT device without stimulation

Anesthesia alone

Experimental: Transcranial Electric Stimulation Therapy (TEST)

TEST involves bifrontal electrical brain stimulation at a dose below the seizure threshold, applied in the same manner as standard electroconvulsive therapy (ECT), with scalp electrodes, under anesthesia, using a standard ECT device (modified or unmodified) that can deliver a range of doses below seizure threshold.

Device: MagPro TMS Stimulator and coil

TMS measurements of cortical excitability pre and post study intervention

Device: Thymatron System IV

The Thymatron System IV (Somatics LLC, Venice, FL, USA)is an FDA 510(k)-cleared ECT device. For TESt, we will be using it in a non FDA-approved manner--stimulating without intending to induce seizures.

Device: Magnetic Resonance Imaging Scanner

Conventional MRI studies in this protocol are considered non-significant risk (NSR) devices. While operated in research mode, the MRI will be under the International Electrotechnical Commission (IEC) 60601-2-33 First Level Controlled Operating Mode, which allows for research pulse sequences to be used within the FDA/IEC safety limits for MRI devices.

Outcome Measures

Primary Outcome Measures

change in EEG waveforms from pretreatment session baseline to end of treatment session [every treatment throughout course (approximately 3x weekly)]
This measure will determine the presence or absence of a seizure in participants receiving TEST. It will inform the feasibility of consistently not inducing seizures with TEST.
Hopkins Verbal Learning Test-Revised (HVLT-R) [Baseline, End of Phase II (approximately 2 weeks) and end of Phase III (4-13 weeks)and at 2 and 4 weeks post treatment course]
The HVLT-R is a brief (<10 min) well-validated version of the word list delayed recall task that assesses anterograde memory.

Secondary Outcome Measures

Montgomery-Asberg Depression Rating Scale (MADRS), [Baseline, after every treatment (approximately 3x weekly) end of Phase II (approximately 2 weeks), end of Phase III (approximately 4-13 weeks), and during outpatient follow up every two weeks for the first month, then monthly for 5 months]
a 10-item, well validated, scale measuring depressive symptoms often used in ECT clinical trials.
Symptoms of Major Depressive Disorder Scale (SMDDS). [Baseline, after every treatment (approximately 3x weekly), end of Phase II (approximately 2 weeks), end of Phase III (approximately 4-13 weeks), and during outpatient follow up every two weeks for the first month, then monthly for 5 months]
The SMDDS is a 16-item, well validated, participant-administered scale that was developed to meet the recommendations promulgated by the FDA to guide industry in the conduct of depression clinical trials

Eligibility Criteria

Criteria

Ages Eligible for Study:

25 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:

In order to be eligible to participate in this study, an individual must meet all of the following criteria:

Provision of a signed and dated informed consent form.
Stated willingness to comply with all study procedures and availability for the duration of the study.
Male or female, ages 25 through 64 years.
Meeting structured clinical interview for the DSM 5 (SCID) criteria for major depressive disorder, bipolar I disorder, or bipolar II disorder.
Currently have TRD as defined by a major depressive episode with lack of remission of depressive symptoms following two trials of different medication or one medication trial and one rTMS trial approved for unipolar or bipolar depression at adequate dosage and duration treatment consistent with an Antidepressant Treatment History Form (ATHF) confidence level >=3.
Score >= 25 on the Montgomery-Asberg Depression Rating Scale (MADRS) and a score >=2 on item 1 at screening.
Score <=12 on the Young Mania Rating Scale (YMRS) and a score <= 1 on item 1 at screening.
Willingness to: (a) provide written permission, as requested, to allow any and all forms of communication between the Investigator/Research Staff and any healthcare provider who currently provides and/or has provided service to the patient/subject within two years of study enrollment; and (b) provide the name and verifiable contact information of a person whom they trust to be an emergency contact whom research staff is at liberty to contact for the duration of study participation and who could serve as a legally authorized representative (LAR) if needed.
Agreement to remain on the same daily dose of all psychiatric medication(s) without taking any new psychiatric medication(s) for a minimum of 6 weeks (42 days) prior to the baseline assessment and through the completion of Study Phase III (Study Phase IV is the 6-month Follow-up Phase) unless advised otherwise by the Investigator
Agreement that dosage reduction of any medication taken for a psychiatric condition must be completed at least 4 weeks (28 days) prior to the baseline assessment and must remain unchanged thereafter through the completion of Study Phase III (Study Phase IV is the 6- month Follow-up Phase), unless advised otherwise by the Investigator
Agreement to remain on the same daily dose of psychiatric medication from the start of the baseline assessment / Phase I through the completion of the final treatment Study Phase III (Study Phase IV is the 6-month Follow-up Phase), unless advised otherwise by the Investigator.
For females of reproductive potential: use of contraception, which in the opinion of the Investigator is highly effective, for at least 1 month prior to screening and agreement to use such a method during study participation, except during the 6-month follow up.
Ability of the participant to understand and be willing to sign a written informed consent document as determined by the Investigator.

ECLUSION CRITERIA:

An individual who meets any of the following criteria will be excluded from participation in this study:

Pregnancy or nursing or women planning to become pregnant during study period, except for the 6-month follow up phase.
A history of addiction to, dependence on, abuse of, or misuse of alcohol or any controlled, illicit, or illegal substance (excluding nicotine) within the past one year
Expression of recent or current active suicidal ideas and an explicit plan or intent, in the opinion of the Investigator or answering YES to questions 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) or scoring >4 on Montgomery-Asberg Depression Rating Scale (MADRS) item 10.
Presence of any disease, medical condition or physical condition that, in the opinion of the Investigator, may compromise, interfere with, limit, effect or reduce the:
subject s ability to participate in any of the items listed in the Schedule of Activities
integrity of the data or
subject s ability to complete the full duration of the study.
Mood disorder is, in the opinion of the Investigator, significantly influenced or caused by an underlying medical or neurological condition, for example, multiple sclerosis or fibromyalgia
History of serious, potentially life-threatening reaction to methohexital or succinylcholine.
Clinically significant psychiatric comorbidity as determined by clinical interview and in the opinion of the Investigator
Past or present medical or neurological condition, disease, disorder or injury that, in the opinion of the Investigator, may significantly increase the potential risks of study participation, reduce or compromise a subject s ability to fully comply with all study requirements for the duration of the study or may compromise the integrity of the data. Past or present medical or neurological condition, disease, disorder or injury that, in the opinion of the Investigator, may significantly increase the potential risks of study participation, reduce or compromise a subject s ability to fully comply with all study requirements for the duration of the study or may compromise the integrity of the data.
History of seizure except those therapeutically induced by ECT, except for childhood febrile seizures.
History of any of the following:
intracranial surgery
cranial metal implants
presence of devices that may be affected by MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator, vagus nerve stimulator
history of head trauma associated with a brain imaging study that shows probable or definite evidence of a post-traumatic abnormality as determined by a neuroradiologist and which the Investigator deems clinically significant at screening.
Any of the following treatment histories:

Failure to respond to adequate ECT treatment consistent with an ATHF confidence level

=3 in current or any previous episode

Lifetime history of treatment with deep brain stimulation

Use of any investigational drug or device within 4 weeks of the screening

Inability to pass the Evaluation to Sign A Consent Form test for adequate comprehension of the study for any reason including limitations related to use of the English language.
Positive HIV test.
Being an NIMH employee or an immediate family member of an NIMH employee.
Presence of any condition that, in the judgment of the investigator, may hinder completion of the procedures required by the study protocol.