iLAST for Depression

Overseen By Paul S Rohde

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Mental Health (NIMH)

Must be taking: Psychotropic medications

Must not be taking: Investigational drugs

Disqualifiers: Substance abuse, Serious medical illness, Seizure history, Psychotic disorder, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 8

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new method for delivering electroconvulsive therapy called Individualized Low Amplitude Seizure Therapy (iLAST), which might treat severe depression with fewer side effects like memory loss. Researchers aim to determine if iLAST is safe and practical for patients with major depressive disorder. Suitable candidates for this trial include those with major depressive disorder who qualify for traditional electroconvulsive therapy. Participants will undergo several tests and receive treatment over up to 20 weeks. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this innovative therapy.

Do I have to stop taking my current medications for the trial?

You must be on a stable dose of all psychotropic medications for 4 weeks before the trial and cannot change them during the experimental phase unless advised by the Investigator.

What prior data suggests that iLAST is safe for treating depression?

Research has shown that both treatments under study, Transcranial Magnetic Stimulation (TMS) and Electroconvulsive Therapy (ECT), have promising safety records for treating depression.

TMS is considered safe and generally well-tolerated. A specific type of TMS, called theta burst stimulation, was reviewed and found effective with a good safety record. Side effects are usually mild, such as headaches or scalp discomfort, and they don't last long.

ECT is already a well-known treatment for severe depression. It has proven effective and is often safer than some medications. However, ECT can cause side effects like memory problems or confusion. This trial explores new methods, like iLAST, to reduce these side effects.

Overall, both treatments have been thoroughly studied and are considered safe for treating depression. However, since this trial is in an early phase, the safety of iLAST is still being evaluated. Participants are closely monitored for any side effects to ensure their safety. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Individualized Low Amplitude Seizure Therapy (iLAST) for depression because it offers a novel approach compared to standard treatments like antidepressant medications and electroconvulsive therapy (ECT). iLAST uses controlled, low-amplitude seizures, which may reduce side effects typically associated with higher amplitude seizures in traditional ECT. This method aims to maintain the therapeutic benefits of ECT while enhancing patient comfort and safety. Additionally, the trial incorporates advanced techniques like transcranial magnetic stimulation (TMS) and MRI to better understand brain changes, potentially leading to more personalized and effective depression treatments.

What evidence suggests that iLAST might be an effective treatment for depression?

Research has shown that electroconvulsive therapy (ECT), one of the treatments in this trial, effectively treats major depression. Studies often find that it can lead to complete symptom relief. ECT can also quickly ease severe depression and reduce suicidal thoughts, though it may cause side effects like memory loss.

Transcranial magnetic stimulation (TMS) is another treatment option in this trial. Many studies have proven that it significantly lessens depression symptoms. TMS is generally safe and well-tolerated, offering a good balance between benefits and risks. Both treatments provide promising options for people with severe depression. ^{2 5 6 7 8}

Who Is on the Research Team?

Sarah H Lisanby, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Are You a Good Fit for This Trial?

Adults aged 22-70 with major depressive disorder eligible for ECT can join this trial. They must understand the study, consent to it, follow a strict treatment schedule, and not change their psychiatric medications during Phase II. Women of childbearing age should use birth control and have a negative pregnancy test.

Inclusion Criteria

You have been diagnosed with major depressive disorder using a specific interview called the structured clinical interview for the DSM-5.

Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document

I am eligible for or currently receiving maintenance electroconvulsive therapy (ECT).

Exclusion Criteria

My serious health conditions are well-managed and won't affect my study participation.

Pregnant or nursing women or women who plan to become pregnant during the study period.

You have had issues with drugs or alcohol in the past 6 months, except for nicotine and caffeine.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Phase I

Baseline assessments including MRI, MEG, TMS, and SEP

1 week

Multiple visits (in-person)

Phase II

Seven sessions of iLAST under general anesthesia, EEG, mood and side effect interviews

2.5 weeks

7 visits (in-person)

Phase III

Routine clinical management with optional conventional ECT and post-course measures

At least 1 week

Multiple visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Electroconvulsive Therapy (ECT)
• Individualized Low Amplitude Seizure Therapy (iLAST)
• Transcranial Magnetic Stimulation (TMS)

Trial Overview

The iLAST method is being tested as an alternative to traditional ECT for treating severe depression. It involves MRI scans, brain activity recordings (MEG), electrical stimulation (TMS), nerve function tests (SEP), and interviews about mood and side effects over three phases lasting up to 20 weeks.

How Is the Trial Designed?

Group I: TMS Experimental Treatment 1 Intervention

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

Group II: MRI Experimental Treatment 1 Intervention

Structural and functional neuroimaging pre and post ECT treatment

Group III: ECT Experimental Treatment 1 Intervention

ECT treatment, Within subject cross-over

Who Is Running the Clinical Trial?

National Institute of Mental Health (NIMH)

Lead Sponsor

Trials

3,007

Recruited

2,852,000+

Published Research Related to This Trial

The novel 2-step intensity-modulated arc therapy (IMAT) techniques showed equal or improved plan quality compared to traditional methods like direct machine parameter optimization (DMPO) and were superior to commercial volumetric arc therapy (SMARTARC) techniques in a study involving various complex target volumes.

The 2-step IMAT techniques demonstrated significant improvements in plan quality, with reductions in composite objective value (COV) by factors of 1.4 to 2.4 for different cases, indicating their potential for effective and efficient radiation therapy adaptation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fast intensity-modulated arc therapy based on 2-step beam segmentationa. Bratengeier, K., Gainey, M., Sauer, OA., et al.[2017]

The implementation of 2-step intensity modulated arc therapy (IMAT) in a computerized treatment planning system showed significant improvements in dose uniformity for both phantom and clinical cases, indicating its efficacy in delivering targeted radiation therapy.

In a clinical case, optimizing segment weights and widths reduced the maximum dose to the target from 114% to 107% and increased the minimum dose from 87% to 97%, demonstrating enhanced treatment precision and safety for surrounding organs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Two-step intensity modulated arc therapy (2-step IMAT) with segment weight and width optimization. Sun, J., Chew, TY., Meyer, J.[2021]

The study developed a real-time electromagnetic-guided dynamic multileaf collimator (DMLC) tracking system for intensity-modulated arc therapy (IMAT), which significantly improved dose delivery to moving targets in lung and prostate cancer cases, with only 1.6% and 1.2% of dose points failing the accuracy test compared to 34% and 14% without tracking.

The DMLC tracking system maintained the same treatment delivery time as traditional methods, demonstrating that it enhances treatment precision without sacrificing efficiency.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Electromagnetic-guided dynamic multileaf collimator tracking enables motion management for intensity-modulated arc therapy. Keall, PJ., Sawant, A., Cho, B., et al.[2021]

The development of new anti-epileptic drugs (AEDs) allows for more personalized treatment plans based on individual patient needs and responses, highlighting the importance of tailoring therapy to each person's unique condition.

Successful AEDs should possess optimal characteristics such as efficacy, tolerability, and cost-effectiveness, which are essential for achieving better seizure control and addressing the broader goals of epilepsy management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ideal characteristics of antiepileptic therapy: an overview of old and new AEDs. Steinhoff, BJ., Hirsch, E., Mutani, R., et al.[2019]

Intensity-modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) effectively spares the hippocampus and other organs at risk, achieving significant dose reductions compared to conventional methods, with a 65% reduction in parotid gland doses and a 50% reduction in maximum doses.

The IMAT plans demonstrated high accuracy and conformity, with an average delivery accuracy of 98.1% and compliance with RTOG 0933 criteria, suggesting it is a safe and efficient treatment option that could improve the quality of life for patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential for reduced radiation-induced toxicity using intensity-modulated arc therapy for whole-brain radiotherapy with hippocampal sparing. Pokhrel, D., Sood, S., Lominska, C., et al.[2018]

A 'start low, go slow' approach to titrating antiseizure medications (ASMs) is recommended to minimize the risk of severe side effects and improve patient tolerability, especially for common central nervous system-related issues like drowsiness and dizziness.

When switching or adding ASMs, careful management and communication with patients are crucial to ensure effective disease control while minimizing the overall drug load, which can help reduce toxicity and improve treatment adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The importance of drug titration in the management of patients with epilepsy. Seiden, LG., Connor, GS.[2022]

In a study of 25 depressed patients undergoing unilateral ECT, those receiving moderately suprathreshold (2.5T) treatments exhibited significantly stronger seizure activity, indicated by greater ictal spectral amplitude and coherence, which may enhance therapeutic outcomes.

A multivariate ictal EEG model was able to accurately differentiate between treatment intensity groups with 90% accuracy, suggesting it could be a valuable tool for optimizing ECT stimulus intensity in clinical settings.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The ictal EEG as a marker of adequate stimulus intensity with unilateral ECT. Krystal, AD., Weiner, RD., Coffey, CE.[2022]

In a study involving nine children with medically intractable epilepsy, high-dose intravenous levetiracetam (IV-LEV) at doses averaging 228 mg/kg/day effectively resolved acute repetitive seizures in eight out of nine patients.

IV-LEV was well tolerated with no significant complications, and seven children experienced a reduction in seizure frequency, indicating its potential as a safe and effective treatment for acute seizure exacerbations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy. Depositario-Cabacar, DT., Peters, JM., Pong, AW., et al.[2018]

Transitional polytherapy, which involves gradually introducing a new antiepileptic drug (AED) while adjusting the dose of the existing medication, is the preferred method for switching between monotherapies in epilepsy treatment to avoid adverse effects and seizure exacerbation.

The choice between a fixed-dose or flexible titration strategy during this transition depends on the patient's current condition: a fixed strategy is best when there are no adverse effects, while a flexible approach is necessary when patients are experiencing side effects from their current medication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions. Garnett, WR., St Louis, EK., Henry, TR., et al.[2021]

Up to 70% of people with epilepsy can achieve seizure freedom with optimal antiepileptic drug (AED) therapy, but the remaining 30% may require more complex treatment strategies, including add-on therapy with a second AED if the first is well tolerated.

Effective management of epilepsy relies on accurately classifying seizure types and syndromes, monitoring both seizure control and side effects, and carefully selecting drug combinations to minimize interactions and maximize adherence.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The use of antiepileptic drugs--principles and practice. Sander, JW.[2022]

The study demonstrated that dynamic multileaf collimator (DMLC) tracking during intensity-modulated arc therapy (IMAT) significantly improved dose delivery to moving tumors, reducing the failure rate of dose distribution from 38% to 0.7% for lung tumors and from 19% to 0% for prostate tumors.

Using a single kV imager for tracking allowed for real-time adjustments to the treatment plan, effectively maintaining accurate dose distributions even with tumor motion, showcasing the potential for enhanced treatment efficacy in radiation therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Image-based dynamic multileaf collimator tracking of moving targets during intensity-modulated arc therapy. Poulsen, PR., Fledelius, W., Cho, B., et al.[2021]

In a study of 17 children with nocturnal or early-morning seizures, adjusting their evening doses of antiepileptic drugs resulted in a significant response, with 64.7% achieving seizure freedom and 88.2% experiencing at least a 50% reduction in seizures after a mean follow-up of 5.3 months.

The approach was safe, as none of the children experienced worsening seizures, and only two reported mild side effects, indicating that differential dosing can be an effective and well-tolerated strategy for managing certain types of epilepsy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Higher evening antiepileptic drug dose for nocturnal and early-morning seizures. Guilhoto, LM., Loddenkemper, T., Vendrame, M., et al.[2018]

In a study of 44 patients on monotherapy with a drug within the therapeutic range, 75% experienced a reduction in seizure frequency, highlighting the efficacy of this treatment approach.

The treatment showed a 90% improvement in Primary Generalized seizures, suggesting it is particularly effective for this type, and supports the recommendation of monotherapy as a first-line treatment due to its manageable nature and lower toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Evaluation of the effectiveness of monotherapy in the treatment of epilepsy]. Brignolio, F., Verzè, L., Baruchello, M.[2013]

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