Title: Safety and Feasibility of Individualized Low Amplitude Seizure Therapy (iLAST)

NCT03895658 | Withdrawn Phase 1 FDA Device

• 2 other identifiers: 19007319-M-0073
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Background: Electroconvulsive therapy (ECT) is used to treat people with severe depression. During ECT, the brain is given electric pulses that cause a seizure. Although it is effective, it can cause side effects, including memory loss. Researchers want to study a new way to give ECT called iLAST. Objective: To see if iLAST is safe and feasible in treating depression. Eligibility: People ages 22 70 years old who have major depressive disorder and are eligible for ECT Design: Participants will be screened under protocol 01-M-0254. This includes: Medical and psychiatric history and exam Blood and urine tests Participants will be inpatients at the Clinical Center. They study has 3 phases and will last up to 20 weeks. Phase I will last 1 week. It includes: MRI: Participants will lie in a scanner that takes pictures of the body MEG: A cone over the participant s head will record brain activity. TMS: A wire coil placed on the participant s scalp will produce an electrical current to affect brain activity. SEP: An electrode on the participant s wrist will give a small electrical shock to test nerve function. Phase II will last 2 and a half weeks. It includes: Seven sessions of iLAST under general anesthesia. Participants may also get standard ECT. EEG: A small electrode placed on the participant s scalp will record brain waves. Interviews about mood, symptoms, and side effects. Participants facial expressions may be video recorded. TMS Phase III will last at least 1 week. It will include: MRI EEG TMS MEG Standard ECT if needed. Participants will have sessions every other day, 3 times a week.

Conditions

Unipolar Depression

Keywords

Brain Stimulation; Neurocognitive; Major Depressive Disorder (MDD)

Outcome Measures

Primary Outcomes (1)

• Successful seizure induction as measured by topographical EEG and motor manifestations, vital signs, ECG, subjective side effect scale, and adverse events/significant adverse events

  Successful seizure induction as measured by topographical EEG and motor manifestations, vital signs, ECG, subjective side effect scale, and adverse events/significant adverse events

  ongoing

Secondary Outcomes (1)

• Neurocognitive battery known to be sensitive to cognitive effects of ECT, with alternative versions to avoid practice effects; Amplitude-titrated seizure threshold (STa), measured electrical motor threshold (MT), and simulated MT derived from re...

  Ongoing

Study Arms (3)

ECT

EXPERIMENTAL

ECT treatment, Within subject cross-over

Device: Thymatron (R) System IV paired with 4X1 HDECT

MRI

EXPERIMENTAL

Structural and functional neuroimaging pre and post ECT treatment

Device: MRI

TMS

EXPERIMENTAL

Transcranial magnetic stimulation measurements of cortical excitability pre and post ECT treatment

Device: MagPro TMS stimulator and coil

Interventions

MRI DEVICE

Structural and functional neuroimaging pre and post ECT treatment

MRI

MagPro TMS stimulator and coil DEVICE

Transcranial magnetic stimulation measurements of cortical excitability pre and post ECT treatment

TMS

Thymatron (R) System IV paired with 4X1 HDECT DEVICE

Multi-Channel Stimulation Interface (Model 4X1 HDECT)

ECT

Eligibility Criteria

• Age: 22 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female, 22-70 years old
• Use of effective method of birth control for women of childbearing capacity. Women who are able to get pregnant must be willing to use at least one form of effective birth control during the entire period of study participation (or until last clinical labs and rating) and have a negative pregnancy test at screening.
• DSM-5 diagnosis of major depressive disorder, confirmed by the structured clinical interview for the DSM 5 (SCID)
• Eligible for ECT, including patients receiving maintenance ECT
• Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document
• Subjects are willing and able to adhere to the intensive treatment schedule and all required study procedures
• On a stable dose of all psychotropic medications (no new medications, discontinuations or dose changes) for 4 weeks prior to baseline assessment and agreement not to change psychotropic medications during the experimental phase (Phase II) of the study, unless advised otherwise by the Investigator.

You may not qualify if:

• Pregnant or nursing women or women who plan to become pregnant during the study period.
• Current or recent (within the past 6 months) substance abuse or dependence (excluding nicotine and caffeine)
• Current serious medical illness, such as high blood pressure, diabetes, heart or lung disease that is not controlled by treatment and/or judged by the investigators to significantly affect the validity of the study or the safety of study participation.
• History of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, concussion resulted in loss of consciousness or hospitalization, cranial metal implants that are not safety-compatible with magnetic resonance imaging (MRI) and/or electroconvulsive therapy (ECT), known structural brain lesion, devices that may be affected by TMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator, vagus nerve stimulator)
• Diagnosed with the following conditions (current unless otherwise stated):
• Any other current primary mood, anxiety, or psychotic disorder
• Depression secondary to a general medical condition, or substance-induced
• Psychotic disorder (lifetime), including schizoaffective disorder, or major depression with psychotic features in the current episode
• Eating disorder (current or within the past year)
• Obsessive compulsive disorder (current or within the past year)
• Post-traumatic stress disorder (current or within the past year)
• ADHD (currently being treated)
• Subjects meeting criteria of any psychiatric illness based upon DSM-5, which in the judgment of the Investigator, may hinder the subjects in completing the procedures required by the study protocol
• Actively suicidal
• Increased risk of complications from seizures, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication at a dose that significantly alters seizure threshold, as determined by the investigators.

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)

• Luber B, Nobler MS, Moeller JR, Katzman GP, Prudic J, Devanand DP, Dichter GS, Sackeim HA. Quantitative EEG during seizures induced by electroconvulsive therapy: relations to treatment modality and clinical features. II. Topographic analyses. J ECT. 2000 Sep;16(3):229-43. doi: 10.1097/00124509-200009000-00003.

  PMID: 11005044 BACKGROUND

• Lisanby SH, Maddox JH, Prudic J, Devanand DP, Sackeim HA. The effects of electroconvulsive therapy on memory of autobiographical and public events. Arch Gen Psychiatry. 2000 Jun;57(6):581-90. doi: 10.1001/archpsyc.57.6.581.

  PMID: 10839336 BACKGROUND

• Lisanby SH, Luber B, Schlaepfer TE, Sackeim HA. Safety and feasibility of magnetic seizure therapy (MST) in major depression: randomized within-subject comparison with electroconvulsive therapy. Neuropsychopharmacology. 2003 Oct;28(10):1852-65. doi: 10.1038/sj.npp.1300229.

  PMID: 12865903 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Depressive Disorder; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Sarah H Lisanby, M.D.

  National Institute of Mental Health (NIMH)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 28, 2019
• First Posted: March 29, 2019
• Study Start: February 26, 2025
• Primary Completion: February 26, 2025
• Study Completion: February 26, 2025
• Last Updated: February 27, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Starting 6 months after publication and 10 years thereafter.
• Access Criteria: Data may be shared with investigators and institutions with an FWA or operating under the Declaration of Helsinki (DoH) and reported at the time of continuing review. Sharing with investigators without an FWA or not operating under the DoH will be submitted for prospective IRB approval. Submissions to NIH-sponsored or supported databases and repositories will be reported at the time of Continuing Review. Submission to non-NIH sponsored or supported databases and repositories will be submitted for prospective @@@@@@IRB approval.

Locations

US (1)