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

Trial Summary

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 data supports the idea that iLAST for Depression is an effective treatment?

The available research does not provide any data on iLAST for Depression. Instead, it focuses on treatments for epilepsy, discussing the effectiveness of different drug therapies for managing seizures. Therefore, there is no information here to support the effectiveness of iLAST for Depression. ^{1 2 3 4 5}

What safety data exists for iLAST or related therapies for depression?

The provided research does not contain safety data for iLAST or related therapies such as ECT, TMS, or rTMS for depression. The studies focus on intensity-modulated arc therapy (IMAT) for radiotherapy, which is unrelated to the treatments in question. ^{6 7 8 9 10}

Is the treatment iLAST a promising treatment for depression?

Yes, iLAST is a promising treatment for depression because it offers a personalized approach that could improve therapeutic outcomes by adjusting the treatment intensity to the individual's needs. ^{1 2 11 12 13}

What is the purpose of this trial?

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.

Research Team

Sarah H Lisanby, M.D.

Principal Investigator

National Institute of Mental Health (NIMH)

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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 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]

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]

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 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]

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]

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 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]

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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

[Evaluation of the effectiveness of monotherapy in the treatment of epilepsy]. [2013]

2. United States pubmed.ncbi.nlm.nih.gov

Higher evening antiepileptic drug dose for nocturnal and early-morning seizures. [2018]

3. United Arab Emirates pubmed.ncbi.nlm.nih.gov

Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions. [2021]

4. Denmark pubmed.ncbi.nlm.nih.gov

The ideal characteristics of antiepileptic therapy: an overview of old and new AEDs. [2019]

5. United States pubmed.ncbi.nlm.nih.gov

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

6. United States pubmed.ncbi.nlm.nih.gov

Fast intensity-modulated arc therapy based on 2-step beam segmentationa. [2017]

7. United States pubmed.ncbi.nlm.nih.gov

Potential for reduced radiation-induced toxicity using intensity-modulated arc therapy for whole-brain radiotherapy with hippocampal sparing. [2018]

8. United States pubmed.ncbi.nlm.nih.gov

Electromagnetic-guided dynamic multileaf collimator tracking enables motion management for intensity-modulated arc therapy. [2021]

9. United States pubmed.ncbi.nlm.nih.gov

Image-based dynamic multileaf collimator tracking of moving targets during intensity-modulated arc therapy. [2021]

10. England pubmed.ncbi.nlm.nih.gov

Two-step intensity modulated arc therapy (2-step IMAT) with segment weight and width optimization. [2021]

11. United States pubmed.ncbi.nlm.nih.gov

The importance of drug titration in the management of patients with epilepsy. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy. [2018]

13. United States pubmed.ncbi.nlm.nih.gov

The ictal EEG as a marker of adequate stimulus intensity with unilateral ECT. [2022]