Low Amplitude Pulse Seizure Therapy for Suicidal Thoughts
(LAP-ST vs ECT Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2 & 3
Recruiting
Sponsor: Michigan State University
Disqualifiers: Pregnancy, Neurological disorder, Dementia, others
No Placebo Group
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This protocol proposes an initial randomized clinical trial that includes all patients with suicidal ideation (SI) at baseline, and with SI as the primary outcome measure to examine whether Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) treatment has more magnitude and rate of remission of SI as conventional pulse amplitude Right Unilateral Electroconvulsive Therapy (RUL ECT) (based on our prior secondary analysis). Our central hypothesis is that RUL LAP-ST has significantly less cognitive/memory side effects (no memory side effects were noted in our prior studies for 500mA and 600mA) and thus is more favorable in terms of side effects compared to RUL conventional pulse amplitude ECT, while maintaining better anti-suicidal effect.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify that you must stop taking your current medications, but it mentions there should be no anticipated need to change psychotropic medications (medications affecting mood, perception, or behavior) during the study, except in urgent situations.
What data supports the effectiveness of Low Amplitude Pulse Seizure Therapy for reducing suicidal thoughts?
Is Low Amplitude Pulse Seizure Therapy safe for humans?
How does Low Amplitude Pulse Seizure Therapy differ from other treatments for suicidal thoughts?
Low Amplitude Pulse Seizure Therapy (LAP-ST) is unique because it uses a lower electrical pulse amplitude compared to standard electroconvulsive therapy (ECT), which may reduce cognitive side effects while still effectively reducing suicidal thoughts more quickly. This makes it potentially safer and faster-acting than traditional ECT methods.134511
Research Team
NA
Nagy A Youssef, MD, PhD
Principal Investigator
Pine Rest Christian Mental Health Services & Michigan State University
Eligibility Criteria
This trial is for patients with suicidal thoughts or mood disorders like major depressive disorder, bipolar disorder, psychosis, and schizoaffective disorder. Participants must be experiencing these conditions at the start of the study.Inclusion Criteria
I have been diagnosed with a major depressive episode as per DSM-5.
Use of effective method of birth control for women of child-bearing capacity
I am between 18 and 90 years old.
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Exclusion Criteria
History of neurological disorder if deemed by the treating ECT physician or PI to pose a significant risk with ECT, or if there is any metal in the head or history of known structural brain lesion or skull defect that is deemed to affect cognition or safe ECT treatment
I do not have a serious condition that could worsen with ECT or affect my thinking.
I am not pregnant, planning to become pregnant, or breastfeeding during the study.
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Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive either RUL LAP-ST or RUL ECT to assess remission of suicidal ideation and cognitive side effects
4 weeks
Multiple sessions per week
Follow-up
Participants are monitored for safety and effectiveness after treatment
4 weeks
Treatment Details
Interventions
- Low Amplitude Pulse Seizure Therapy (Procedure)
- Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy (Procedure)
Trial OverviewThe trial is testing a new treatment called Right Unilateral Low-Amplitude Pulse - Seizure Therapy (RUL LAP-ST) against standard Right Unilateral Electroconvulsive Therapy (RUL ECT). The focus is on which treatment better reduces suicidal thoughts without causing memory issues.
Participant Groups
2Treatment groups
Experimental Treatment
Active Control
Group I: RUL LAP-ST (Low-Amplitude Pulse Seizure Therapy - Right Unilateral)Experimental Treatment1 Intervention
Low Amplitude Pulse Seizure Therapy RUL ECT at 600mA (or 700mA)
Group II: RUL ECT (Electroconvulsive Therapy)Active Control1 Intervention
RUL Conventional pulse amplitude Electroconvulsive Therapy (ECT)
Low Amplitude Pulse Seizure Therapy is already approved in United States, European Union, Switzerland for the following indications:
🇺🇸 Approved in United States as Electroconvulsive Therapy (ECT) for:
- Major depressive disorder
- Catatonia
- Acute schizophrenic exacerbations
- Bipolar disorder
- Mania
🇪🇺 Approved in European Union as Electroconvulsive Therapy (ECT) for:
- Severe depressive episodes
- Catatonia
- Treatment-resistant schizophrenic disorders
🇨🇭 Approved in Switzerland as Electroconvulsive Therapy (ECT) for:
- Severe depressive episodes
- Catatonia
- Treatment-resistant schizophrenic disorders
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Pine Rest Christian Mental Health ServicesGrand Rapids, MI
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Who Is Running the Clinical Trial?
Michigan State University
Lead Sponsor
Trials
202
Patients Recruited
687,000+
Pine Rest Christian Mental Health Services
Collaborator
Trials
6
Patients Recruited
520+
References
Selecting right unilateral placement to facilitate continuation of electroconvulsive therapy following prolonged seizures. [2021]Available literature remains limited in the identification of risk factors for prolonged seizures in electroconvulsive therapy and much less is reported about the continuation of electroconvulsive therapy after prolonged seizures. We describe two cases with prolonged seizures early in their course of electroconvulsive therapy and the subsequent adjustment made that allowed for safe and effective continuation of electroconvulsive therapy. In both cases, right unilateral electroconvulsive therapy was continued at a suprathreshold stimulus dose of six times relative to seizure threshold. Both patients continued their course of electroconvulsive therapy with no further episodes of prolonged seizures. They did not experience significant cognitive side effects and were discharged after showing marked improvement in their clinical symptoms. Prolonged seizures do not preclude the use of electroconvulsive therapy. The selection of ultrabrief right unilateral electroconvulsive therapy allows for a higher suprathreshold dose with less cognitive side effects compared to bilateral placements. This mitigates the risk of prolonged seizures, allowing for safe and effective continuation of electroconvulsive therapy.
Duration of Treatment in Electroconvulsive Therapy Among Patients Beginning With Acute Course Right Unilateral Brief Pulse Stimuli. [2023]Right unilateral brief pulse (RUL-BP) electroconvulsive therapy (ECT) has been adopted as a technique for reducing the cognitive side effects of ECT relative to sine wave or bilateral treatments, but it is unknown how often patients are transitioned to alternative electrode placements. This study analyzes time in first lifetime acute course RUL-BP ECT.
Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral Electroconvulsive Therapy: A Pilot Double-Blinded Randomized Clinical Trial. [2023]Background: Although treatment guidelines support use of electroconvulsive therapy (ECT) for acute suicidality, it is associated with cognitive side effects. The effect of Low Amplitude Seizure Therapy (LAP-ST) on suicidality is unknown. Our prior precision LAP-ST (pLAP-ST) performing titrating in the current domain has provided initial proof of concept data in humans of its advantage in terms of reduction of cognitive side effects. The aims of this report are to: 1) compare LAP-ST (at 500mA) versus standard Right Unilateral (RUL) ECT (at 900 mA) in terms of magnitude of remission of suicidality in a randomized allocation and 2) compare the speed of remission of suicidality between LAP-ST versus RUL ECT. Methods: Patients were randomized to either LAP-ST or RUL ECT. The scores pertaining to the suicidal ideation (SI) item on the Montgomery-Åsberg Depression Rating Scale (MADRS) were analyzed using descriptive analysis and no confirmatory statistical analysis was performed due to a priori sample size limitations for this pilot study. SI item remission was defined as 2 or below on this item. Results: Eleven patients with major depressive episode (MDE) of mainly unipolar or bipolar disorders signed consent. Of these, 7 were eligible and were randomized and included in the analysis; all were actively suicidal at baseline (suicide item above 2), except 1 patient who had suicide item at 2 in the RUL ECT group. Suicidality remitted on average by session 3 and remission occurred for all patients by session 4. The SI mean score improvement from baseline to endpoint for LAP-ST was 5.1 and for RUL ECT was 3.0. Conclusions: LAP-ST has larger effect size and speed of remission of suicidality compared to standard RUL ECT. Future studies are warranted for replicating these findings. (ClinicalTrials.gov ID: NCT02583490).
Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man. [2022]Current pulse amplitude used in clinical ECT may be higher than needed. Reducing pulse amplitude may improve focality of the electric field and thus cognitive adverse effects. Here we examine the feasibility, safety, and whether Low Pulse Amplitude Seizure Therapy (LAP-ST, 0.5-0.6A) minimizes cognitive adverse effects while retaining efficacy.
Successful switch from bilateral brief pulse to right unilateral ultrabrief pulse electroconvulsive therapy after failure to induce seizures. [2020]Inducing adequate therapeutic seizures during electroconvulsive therapy (ECT) is sometimes difficult due to a high seizure threshold, even at the maximum stimulus charge. Previous studies have demonstrated that seizure threshold is lower in patients treated with right unilateral ultrabrief pulse (RUL-UBP) ECT than in those treated with bilateral or brief pulse (BL-BP) ECT. Therefore, switching to RUL-UBP ECT may be beneficial for patients in whom seizure induction is difficult with conventional ECT. In the present report, we discuss the case of a patient suffering from catatonic schizophrenia in whom BL-BP ECT failed to induce seizures at the maximum charge. However, RUL-UBP ECT successfully elicited therapeutic seizures and enabled the patient to achieve complete remission. This case illustrates that, along with other augmentation strategies, RUL-UBP ECT represents an alternative for seizure induction in clinical practice.
Rate of continuing acute course treatment using right unilateral ultrabrief pulse electroconvulsive therapy at a large academic medical center. [2022]Right unilateral ultrabrief pulse (RUL-UBP) ECT has emerged as a promising technique for minimizing cognitive side effects of ECT while retaining clinical efficacy, but it is unknown how often patients will require alternative treatment parameters and at what point in the treatment course this occurs. To better define this problem, this study analyzes continuation in RUL-UBP ECT in a retrospective cohort of patients beginning acute course treatment. A single-center retrospective chart review was conducted of adult patients receiving a first lifetime course of ECT from 2010 to 2017 starting with RUL-UBP treatment parameters. 1793 patients met study criteria. Patients received a mean of 10.0 ± 3.2 ECT treatments, of which a mean of 8.4 ± 3.4 were RUL-UBP treatments; proportion using RUL-UBP through 12 treatments was 57.8%. In total, 65.6% of patients were treated with RUL-UPB ECT exclusively. Mean dose increased from 7.6 × seizure threshold at the second RUL-UBP treatment to 14.3 × seizure threshold at the twelfth RUL-UBP treatment. Rates of continuation in RUL-UBP ECT did not differ based on age or on primary diagnosis of major depression vs. bipolar disorder. Among patients beginning acute-course treatment using RUL-UPB ECT, two thirds were treated with these parameters exclusively. Among patients who received twelve RUL-UBP treatments, mean final dose was 14.3 × seizure threshold. Further studies regarding optimal dosing of RUL-UBP ECT are indicated.
Valproate monotherapy in the management of generalized and partial seizures. [2019]For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.
Adjunctive Madopar for ultrarefractory epilepsy? Preliminary observations. [2014]The optimum drug treatment for ultrarefractory epilepsy after failure of seven prior antiepileptic drugs (AEDs) remains uncertain. Prompted by reports that adjunctive amantadine or l-dopa has been useful for children with refractory absence seizures and Lennox-Gastaut syndrome, we studied the utility of dopaminergic agents for adults with ultrarefractory epilepsy.
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.
Treating epilepsy across its different stages. [2021]Epilepsy is a chronic condition requiring long-term treatment with drugs that have intrinsic limitations. Antiepileptic drugs (AEDs) are effective in suppressing seizures but do not alter the disease process. They have a suboptimal tolerability profile and can be teratogenic. Second-generation compounds may be better tolerated but no more effective than traditional AEDs. In this light, as drug therapy is purely symptomatic, acute symptomatic seizures (i.e. seizures occurring in close temporal relationship with acute CNS insults) may require treatment only until recovery or stabilization of the injury. Treatment of the first unprovoked seizure may be considered in patients with abnormal EEG and imaging findings and in those in whom the relapse has severe social, emotional and personal implications. In these cases and in patients with epilepsy (i.e. repeated unprovoked seizures), drugs for partial seizures supported by class I regulatory trials or pragmatic trials are oxcarbazepine in children, carbamazepine or lamotrigine in adults, and lamotrigine or gabapentin in the elderly. Pragmatic trials support use of valproate for generalized seizures, except for women of childbearing age for whom the drug should be tailored to the individual patient. The lowest maintenance dose should be chosen, based on the efficacy and tolerability of the assigned drug. If the first monotherapy fails, the safety profile of a drug is important when opting for another monotherapy or for an add-on therapy. The epilepsy syndrome and the social, psychological and emotional profile of the patient all contribute to the individualization of treatment discontinuation after long-term seizure remission.
Stimulus pulse-frequency-dependent efficacy and cognitive adverse effects of ultrabrief-pulse electroconvulsive therapy in patients with major depression. [2012]: Electroconvulsive therapy (ECT) is a highly effective treatment for major depression. New ECT devices with shorter pulse widths seem to induce seizures more effectively at a lower seizure threshold and with fewer cognitive adverse effects. Suprathreshold right unilateral (RUL) ultrabrief-pulse ECT with pulse widths between 0.25 and 0.30 millisecond seem to be especially effective with regard to efficacy and cognitive adverse effects. A lower pulse frequency (50 pulses per second) in RUL ECT was found to be more efficient than a higher pulse frequency (200 pulses per second) in inducing seizures. However, effective stimulus dose can often be achieved only with high stimulus frequency, whereas the impact of increased stimulus frequency on antidepressant efficacy and cognitive adverse effects is not known.