iLAST for Depression
Recruiting in Palo Alto (17 mi)
Overseen bySarah H Lisanby, M.D.
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Waitlist Available
Sponsor: National Institute of Mental Health (NIMH)
No Placebo Group
Trial Summary
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.
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.12345
What safety data exists for iLAST or related therapies for depression?
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).
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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.
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Treatment Details
Interventions
- Electroconvulsive Therapy (ECT) (Procedure)
- Individualized Low Amplitude Seizure Therapy (iLAST) (Procedure)
- Transcranial Magnetic Stimulation (TMS) (Procedure)
Trial OverviewThe 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
3Treatment groups
Experimental Treatment
Group I: TMSExperimental Treatment1 Intervention
Transcranial magnetic stimulation measurements of cortical excitability pre and post ECT treatment
Group II: MRIExperimental Treatment1 Intervention
Structural and functional neuroimaging pre and post ECT treatment
Group III: ECTExperimental Treatment1 Intervention
ECT treatment, Within subject cross-over
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
National Institutes of Health Clinical CenterBethesda, MD
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Who Is Running the Clinical Trial?
National Institute of Mental Health (NIMH)Lead Sponsor
References
[Evaluation of the effectiveness of monotherapy in the treatment of epilepsy]. [2013]On 44 patients undergoing monotherapy, with total plasma levels of drug therapeutic range, 33 had a reduction of the frequency of seizures, while the remaining 11 were unmodified. There was 90% improvement in Primary Generalized seizures, 73% in Secondary Generalized and 62% in Partial Complex; 27% of PC, 16% of PG and 16% of SG shifted to polytherapy. Considering that monotherapy can be better managed and is less toxic, we can recommend it as first choice treatment in newcomers, as a maintenance therapy, and as treatment of choice for the gradual elimination of therapy.
Higher evening antiepileptic drug dose for nocturnal and early-morning seizures. [2018]We describe 17 children with nocturnal or early-morning seizures who were switched to a proportionally higher evening dose of antiepileptic drugs and were retrospectively reviewed for seizure outcome and side effects. Of 10 children with unknown etiology, clinical presentation was consistent with nocturnal frontal lobe epilepsy (NFLE) in 5 and benign epilepsy with centrotemporal spikes (BECTS) in 3. After a mean follow-up of 5.3 months, 15 patients were classified as responders; 11 of these became seizure free (5 NFLE, 1 BECTS, 5 with structural lesions) and 4 (2 BECTS, 2 with structural lesions) experienced 75-90% reductions in seizures. Among two nonresponders, seizures in one had failed to resolve with epilepsy surgery. Nine subjects (53%) received monotherapy after dose modification, and none presented with worsening of seizures. Two complained of transient side effects (fatigue/somnolence). Differential dosing led to seizure freedom in 64.7% (11/17) of patients, and 88.2% (15/17) experienced ≥ 50% reductions in seizures.
Transitional polytherapy: tricks of the trade for monotherapy to monotherapy AED conversions. [2021]The goal of epilepsy therapy is to help patients achieve seizure freedom without adverse effects. While monotherapy is preferable in epilepsy treatment, many patients fail a first drug due to lack of efficacy or failure to tolerate an initial medication, necessitating an alteration in therapy. Sudden changes between monotherapies are rarely feasible and sometimes deleterious given potential hazards of acute seizure exacerbation or intolerable adverse effects. The preferred method for converting between monotherapies is transitional polytherapy, a process involving initiation of a new antiepileptic drug (AED) and adjusting it toward a target dose while maintaining or reducing the dose of the baseline medication. A fixed-dose titration strategy of maintaining the baseline drug dose while titrating the new medication is preferable when breakthrough seizures are occurring and no adverse effects are present. However, a flexible titration strategy involving reduction of the baseline drug dose to ensure adequate tolerability of the new adjunctive medication is preferred when patients are already experiencing adverse effects. This article reviews pharmacokinetic considerations pertinent for ensuring successful transitional polytherapy with the standard and newer antiepileptic drugs. Practical consensus recommendations "from an expect panel (SPECTRA, Study by a Panel of Experts Considerations for Therapy Replacement and Antiepileptics) for a successful monotherapy" AED conversions are then summarized. Transitional polytherapy is most successful when clinicians appropriately manage the titration strategy and consider pharmacokinetic factors germane to the baseline and new adjunctive medication.
The ideal characteristics of antiepileptic therapy: an overview of old and new AEDs. [2019]New and improved anti-epileptic drugs (AEDs) have made the concept of choice, according to the individual prognosis and probable response to specific regimens, increasingly feasible. Inter-individual variability in syndrome severity and complexity make individualization necessary. We propose three categories of disorder control according to the individual objectives of the patient: (1) seizure control, (2) epilepsy control and ultimately, (3) "epilepsy cure"; the latter remaining a largely idealistic target today. An AED is likely to be successful if it exhibits "optimal" characteristics, such as drug efficacy, tolerability, pharmacokinetics, interactions and cost-effectiveness. This review discusses the "optimal" characteristics of add-on AEDs, which, in addition to seizure control, will contribute to the achievement of epilepsy control and therefore address the currently unmet clinical needs of epilepsy treatment.
The use of antiepileptic drugs--principles and practice. [2022]Up to 70% of people developing epilepsy may expect to become seizure free with optimum antiepileptic drug (AED) therapy. The remaining 30% are the most difficult to treat. Most patients are controlled on a single AED, but a small proportion requires a combination of two agents. Add-on therapy with a second drug, rather than substitution, may be a viable and rational approach in some patients, particularly if the first drug is relatively well tolerated. Precise classification of the type of seizures, as well as the epilepsy syndrome, together with careful recording of both seizures and adverse effects, are essential if rational management decisions are to be made. The goal of therapy should be complete seizure freedom with a single drug taken once or twice a day and without adverse effects. If control is difficult to achieve, the maximum tolerated dose of each drug should be explored, but a balance needs to be struck between adverse effects and control of seizures. In patients in whom treatment appears to be ineffective, the diagnosis of epilepsy and adherence to therapy should be reviewed. Drugs used in combination must be carefully selected, as poor adherence, drug interactions, and toxicity are more likely if more than one drug is prescribed. Agents are usually chosen according to seizure type, patient characteristics, and often by clinician preference. Those that are better tolerated have a low potential for pharmacokinetic and pharmacodynamic interactions, and those that can be easily introduced without any complicated titration schedule have an advantage.
Fast intensity-modulated arc therapy based on 2-step beam segmentationa. [2017]Single or few are intensity-modulated arc therapy (IMAT) is intended to be a time saving irradiation method, potentially replacing classical intensity-modulated radiotherapy (IMRT). The aim of this work was to evaluate the quality of different IMAT methods with the potential of fast delivery, which also has the possibility of adapting to the daily shape of the target volume.
Potential for reduced radiation-induced toxicity using intensity-modulated arc therapy for whole-brain radiotherapy with hippocampal sparing. [2018]The purpose of this study was to retrospectively investigate the accuracy, plan quality, and efficiency of using intensity-modulated arc therapy (IMAT) for whole brain radiotherapy (WBRT) patients with sparing not only the hippocampus (following RTOG 0933 compliance criteria) but also other organs at risk (OARs). A total of 10 patients previously treated with nonconformal opposed laterals whole-brain radiotherapy (NC-WBRT) were retrospectively replanned for hippocampal sparing using IMAT treatment planning. The hippocampus was volumetrically contoured on fused diagnostic T1-weighted MRI with planning CT images and hippocampus avoidance zone (HAZ) was generated using a 5 mm uniform margin around the hippocampus. Both hippocampi were defined as one paired organ. Whole brain tissue minus HAZ was defined as the whole-brain planning target volume (WB-PTV). Highly conformal IMAT plans were generated in the Eclipse treatment planning system for Novalis TX linear accelerator consisting of high-definition multileaf collimators (HD-MLCs: 2.5 mm leaf width at isocenter) and 6 MV beam for a prescription dose of 30 Gy in 10 fractions following RTOG 0933 dosimetric criteria. Two full coplanar arcs with orbits avoidance sectors were used. In addition to RTOG criteria, doses to other organs at risk (OARs), such as parotid glands, cochlea, external/middle ear canals, skin, scalp, optic pathways, brainstem, and eyes/lens, were also evaluated. Subsequently, dose delivery efficiency and accuracy of each IMAT plan was assessed by delivering quality assurance (QA) plans with a MapCHECK device, recording actual beam-on time and measuring planed vs. measured dose agreement using a gamma index. On IMAT plans, following RTOG 0933 dosimetric criteria, the maximum dose to WB-PTV, mean WB-PTV D2%, and mean WB-PTV D98% were 34.9 ± 0.3 Gy, 33.2 ± 0.4 Gy, and 26.0± 0.4Gy, respectively. Accordingly, WB-PTV received the prescription dose of 30Gy and mean V30 was 90.5% ± 0.5%. The D100%, and mean and maximum doses to hippocampus were 8.4 ± 0.3 Gy, 11.2 ± 0.3 Gy, and 15.6 ± 0.4 Gy, on average, respectively. The mean values of homogeneity index (HI) and conformity index (CI) were 0.23 ± 0.02 and 0.96 ± 0.02, respectively. The maximum point dose to WB-PTV was 35.3 Gy, well below the optic pathway tolerance of 37.5 Gy. In addition, compared to NC-WBRT, dose reduction of mean and maximum of parotid glands from IMAT were 65% and 50%, respectively. Ear canals mean and maximum doses were reduced by 26% and 12%, and mean and maximum scalp doses were reduced by 9 Gy (32%) and 2 Gy (6%), on average, respectively. The mean dose to skin was 9.7 Gy with IMAT plans compared to 16 Gy with conventional NC-WBRT, demonstrating that absolute reduction of skin dose by a factor of 2. The mean values of the total number of monitor units (MUs) and actual beam on time were 719 ± 44 and 2.34 ± 0.14 min, respectively. The accuracy of IMAT QA plan delivery was (98.1 ± 0.8) %, on average, with a 3%/3 mm gamma index passing rate criteria. All of these plans were considered clinically acceptable per RTOG 0933 criteria. IMAT planning provided highly conformal and homogenous plan with a fast and effective treatment option for WBRT patients, sparing not only hippocampi but also other OARs, which could potentially result in an additional improvement of the quality life (QoL). In the future, we plan to evaluate the clinical potential of IMAT planning and treatment option with hippocampal and other OARs avoidance in our patient's cohort and asses the QoL of the WBRT patients, as well as simultaneous integrated boost (SIB) for the brain metastases diseases.
Electromagnetic-guided dynamic multileaf collimator tracking enables motion management for intensity-modulated arc therapy. [2021]Intensity-modulated arc therapy (IMAT) is attractive because of high-dose conformality and efficient delivery. However, managing intrafraction motion is challenging for IMAT. The purpose of this research was to develop and investigate electromagnetically guided dynamic multileaf collimator (DMLC) tracking as an enabling technology to treat moving targets during IMAT.
Image-based dynamic multileaf collimator tracking of moving targets during intensity-modulated arc therapy. [2021]Intensity-modulated arc therapy (IMAT) enables efficient and highly conformal dose delivery. However, intrafraction motion may compromise the delivered target dose distribution. Dynamic multileaf collimator (DMLC) tracking can potentially mitigate the impact of target motion on the dose. The purpose of this study was to use a single kV imager for DMLC tracking during IMAT and to investigate the ability of this tracking to maintain the dose distribution.
Two-step intensity modulated arc therapy (2-step IMAT) with segment weight and width optimization. [2021]2-step intensity modulated arc therapy (IMAT) is a simplified IMAT technique which delivers the treatment over typically two continuous gantry rotations. The aim of this work was to implement the technique into a computerized treatment planning system and to develop an approach to optimize the segment weights and widths.
The importance of drug titration in the management of patients with epilepsy. [2022]The variable response to antiseizure medication (ASM) treatment and the numerous drug- and patient-related factors that must be considered when initiating therapy make drug titration to an optimal and tolerable dose an essential component in the pharmacologic treatment of patients with epilepsy. When initiating a new ASM, a "start low, go slow" titration approach is generally recommended and has been shown to reduce the risk of severe idiosyncratic reactions with certain medications and improve tolerability with regard to many frequently occurring central nervous system-related adverse effects (e.g., somnolence, dizziness). Many patients with epilepsy will require medication changes due to lack of efficacy or intolerability of the initial regimen. When this occurs, patients may be switched from one monotherapy to another or receive adjunctive therapy. When transitioning a patient from one ASM to another (referred to as monotherapy conversion or transitional polytherapy), there are several strategies for tapering the baseline ASM depending on the clinical scenario. Regardless of the particular strategy, the goal should be to discontinue the baseline ASM in order to prevent increased toxicity due to drug load. When adding on ASM therapy, flexible titration of the new ASM and adjustment of concomitant ASMs to achieve disease control with the lowest possible drug load (lowest numbers and lowest doses) may help improve tolerability of the add-on therapy. Communication with patients during the initiation of a new therapy may help patients adhere to the titration schedule, allowing them to reach their optimal maintenance dose.
High-dose intravenous levetiracetam for acute seizure exacerbation in children with intractable epilepsy. [2018]We review our experience with high-dose intravenous levetiracetam (IV-LEV) for acute seizure exacerbations in nine children with medically intractable epilepsy. All children had acute repetitive seizures-while on chronic antiepileptic drugs-that either led to hospitalization (eight) or occurred during hospitalization (one), and received doses of IV-LEV of 150 mg/kg/day or greater, with a mean dose of 228 +/- 48 mg/kg/day. Eight of nine children had resolution of the acute repetitive seizures. Seizure frequency was reduced to less than baseline in seven children (seizure-free in two, >/=80% reduction in four, and 50% reduction in one). Except for one child with increased seizures, IV-LEV was well tolerated in all children without complications.
The ictal EEG as a marker of adequate stimulus intensity with unilateral ECT. [2022]Relative stimulus intensity above seizure threshold has been shown to affect therapeutic outcome with unilateral ECT. The authors sought to explore whether a multivariate ictal EEG model would permit ongoing clinical assessment of this parameter. Twenty-five depressed subjects were randomized to either barely (T) or moderately (2.5T) suprathreshold ECT treatments. Seizures in 2.5T subjects had significantly greater ictal spectral amplitude and coherence, greater postictal suppression, and shorter latency until ictal slow-wave onset. A multivariate logistic regression ictal EEG model distinguished between stimulus intensity groups with 90% accuracy. Preliminary evidence suggests a relationship between several ictal EEG indices and therapeutic outcome. A multivariate ictal EEG algorithm holds promise as a tool for clinical determination of adequate stimulus intensity with unilateral ECT.