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

NCT05172271 | Active Not Recruiting FDA Device

• 2 other identifiers: 21003121-M-0031
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder; Bipolar Disorder; Unipolar Major Depression

Keywords

Electroconvulsive Therapy; Major Depressive Disorder; noninvasive brain stimulation; Bipolar Disorder; SEIZURE

Outcome Measures

Primary Outcomes (2)

• Hopkins Verbal Learning Test-Revised (HVLT-R)

  The HVLT-R is a brief (\<10 min) well-validated version of the word list delayed recall task that assesses anterograde memory.

  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

• change in EEG waveforms from pretreatment session baseline to end of treatment session

  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.

  every treatment throughout course (approximately 3x weekly)

Secondary Outcomes (2)

• 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

• 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

Study Arms (2)

Sham TEST

SHAM COMPARATOR

Anesthesia alone

Other: ECT device without stimulation

Transcranial Electric Stimulation Therapy (TEST)

EXPERIMENTAL

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; Device: Thymatron(R) System IV; Device: Magnetic Resonance Imaging Scanner

Interventions

MagPro TMS Stimulator and coil DEVICE

TMS measurements of cortical excitability pre and post study intervention

Transcranial Electric Stimulation Therapy (TEST)

Thymatron(R) System IV DEVICE

The Thymatron(R) 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.

Transcranial Electric Stimulation Therapy (TEST)

Magnetic Resonance Imaging Scanner DEVICE

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.

Transcranial Electric Stimulation Therapy (TEST)

ECT device without stimulation OTHER

Anesthesia alone

Sham TEST

Eligibility Criteria

• Age: 25 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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 or for individuals with bipolar depression, score \>= 25 on the Bipolar Depression Rating Scale (BDRS) 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:

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Prudic J, Sackeim HA, Devanand DP, Krueger RB, Settembrino JM. Acute cognitive effects of subconvulsive electrical stimulation. Convuls Ther. 1994 Mar;10(1):4-24.

  PMID: 8055291 BACKGROUND

• Sackeim HA. Is the Seizure an Unnecessary Component of Electroconvulsive Therapy? A Startling Possibility. Brain Stimul. 2015 Sep-Oct;8(5):851-4. doi: 10.1016/j.brs.2015.07.026. Epub 2015 Jul 17. No abstract available.

  PMID: 26358486 BACKGROUND

• Regenold WT, Noorani RJ, Piez D, Patel P. Nonconvulsive Electrotherapy for Treatment Resistant Unipolar and Bipolar Major Depressive Disorder: A Proof-of-concept Trial. Brain Stimul. 2015 Sep-Oct;8(5):855-61. doi: 10.1016/j.brs.2015.06.011. Epub 2015 Jun 26.

  PMID: 26187603 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depressive Disorder, Major; Bipolar Disorder; Seizures

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Bipolar and Related Disorders; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• William T Regenold, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: DEVICE FEASIBILITY
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 28, 2021
• First Posted: December 29, 2021
• Study Start: November 8, 2022
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): October 31, 2027
• Last Updated: March 17, 2026

Record last verified: 2026-03-13

Data Sharing

• IPD Sharing: Will share
• Shared Documents: CSR
• Time Frame: This study will comply with the NIH Data Sharing Policy and Policy on the Dissemination of NIH-Funded Clinical Trial Information and the Clinical Trials Registration and Results Information Submission rule. @@@Data from this study may be requested from other (non-PGC) researchers indefinitely after the completion of the primary endpoint by contacting William T. Regenold, MDCM, Lead Associate Investigator. @@@Following publication of our study results, we will consider sharing deidentified clinical information and study results of individual participants as well as the study data analysis plan with potential collaborators who provide a methodologically sound proposal, as long as participants gave their permission at consent.
• Access Criteria: IPD will be shared with potential collaborators who provide a methodologically sound proposal, and are willing to sign a data access agreement. The IPD can be used in any analyses, including meta-analyses, that are part of a methodologically sound proposal. The access mechanism will be through contacting study personnel listed in the clinicaltrials.gov study description or by directly contacting William T. Regenold, MDCM, Lead Associate Investigator. Requests will be reviewed by Dr. Regenold and the study PI, Dr. Sarah H. Lisanby.

Locations

US (1)