Low Amplitude Pulse Seizure Therapy for Suicidal Thoughts

(LAP-ST vs ECT Trial)

Overseen By Janelle M Kassien, LMSW

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: Michigan State University

Disqualifiers: Pregnancy, Neurological disorder, Dementia, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 4 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called Low Amplitude Pulse Seizure Therapy to determine if it can reduce suicidal thoughts in individuals with major depression, bipolar disorder, or schizoaffective disorder. The researchers aim to discover if this therapy is as effective as, or better than, standard Electroconvulsive Therapy (ECT), but with fewer memory side effects. Individuals who currently experience suicidal thoughts and are considering ECT as part of their treatment might be suitable for this trial. As a combined Phase 2 and Phase 3 trial, this study evaluates the treatment's effectiveness in an initial group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking mental health advancements.

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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research shows that Low Amplitude Pulse Seizure Therapy (LAP-ST) might cause fewer memory problems than traditional Electroconvulsive Therapy (ECT). Earlier studies found no memory issues with LAP-ST at specific levels (500mA and 600mA), suggesting it could have fewer side effects.

ECT is a common treatment for several conditions and is generally safe, though some people may experience memory problems. Research has well-supported its effectiveness in helping with suicidal thoughts.

Both treatments are generally well-tolerated, but LAP-ST might offer an advantage with fewer memory concerns based on earlier studies. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about Low Amplitude Pulse Seizure Therapy (LAP-ST) because it offers a new approach to treating suicidal thoughts. Unlike traditional electroconvulsive therapy (ECT) that uses higher pulse amplitudes, LAP-ST utilizes lower amplitude pulses, which may reduce side effects while maintaining effectiveness. This could lead to a gentler treatment experience for patients. Additionally, LAP-ST's potential for quick results makes it a promising option in urgent situations where rapid relief is crucial.

What evidence suggests that this trial's treatments could be effective for suicidal thoughts?

Research has shown that Low Amplitude Pulse Seizure Therapy (LAP-ST), a treatment option in this trial, holds promise for reducing suicidal thoughts. Studies have found that LAP-ST reduces these thoughts more quickly and effectively than standard electroconvulsive therapy (ECT), another treatment option in this trial. Previous trials noted that LAP-ST has a larger effect size, suggesting it might be more impactful. Importantly, LAP-ST appears to cause fewer memory side effects compared to conventional ECT, potentially making it a better option for those concerned about cognitive effects. ^{1 3 4 5 6}

Who Is on the Research Team?

Nagy A Youssef, MD, PhD

Principal Investigator

Pine Rest Christian Mental Health Services & Michigan State University

Are You a Good Fit for This Trial?

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 need electroconvulsive therapy as per my doctor's advice.

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

Implanted devices that make ECT unsafe

I do not have a serious condition that could worsen with ECT or affect my thinking.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

Interventions

• Low Amplitude Pulse Seizure Therapy
• Standard Ultra-Brief Right Unilateral Electroconvulsive Therapy

Trial Overview The 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.

How Is the Trial Designed?

Group I: RUL LAP-ST (Low-Amplitude Pulse Seizure Therapy - Right Unilateral) Experimental Treatment 1 Intervention

Low Amplitude Pulse Seizure Therapy RUL ECT at 600mA (or 700mA)

Group II: RUL ECT (Electroconvulsive Therapy) Active Control 1 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

Who Is Running the Clinical Trial?

Michigan State University

Lead Sponsor

Trials

202

Recruited

687,000+

Pine Rest Christian Mental Health Services

Collaborator

Trials

6

Recruited

520+

Published Research Related to This Trial

In a case study of a patient with catatonic schizophrenia, switching from bilateral brief pulse (BL-BP) electroconvulsive therapy (ECT) to right unilateral ultrabrief pulse (RUL-UBP) ECT successfully induced therapeutic seizures when the former failed, leading to complete remission.

This suggests that RUL-UBP ECT may be a valuable alternative for patients who have a high seizure threshold and struggle to achieve adequate seizure induction with conventional ECT methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Successful switch from bilateral brief pulse to right unilateral ultrabrief pulse electroconvulsive therapy after failure to induce seizures. Kawashima, H., Kobayashi, Y., Suwa, T., et al.[2020]

Low Amplitude Seizure Therapy (LAP-ST) demonstrated a greater reduction in suicidal ideation compared to standard Right Unilateral Electroconvulsive Therapy (RUL ECT), with an average improvement score of 5.1 for LAP-ST versus 3.0 for RUL ECT among 7 patients with major depressive episodes.

All patients receiving LAP-ST experienced remission of suicidality by the fourth session, indicating that LAP-ST not only has a larger effect size but also a faster speed of remission compared to RUL ECT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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. Youssef, NA., Ravilla, D., Patel, C., et al.[2023]

In a study of 1383 patients receiving their first course of right unilateral brief pulse (RUL-BP) electroconvulsive therapy (ECT), over 60% continued with RUL-BP parameters throughout their treatment, indicating its effectiveness and acceptance as a primary approach.

Only 37.5% of patients transitioned to bilateral ECT, with younger patients and those with bipolar disorder being more likely to switch, suggesting that RUL-BP may be a preferred option for many patients due to its reduced cognitive side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Duration of Treatment in Electroconvulsive Therapy Among Patients Beginning With Acute Course Right Unilateral Brief Pulse Stimuli. Luccarelli, J., McCoy, TH., Shannon, AP., et al.[2023]

Low Pulse Amplitude Seizure Therapy (LAP-ST) was found to be feasible for inducing seizures in all 22 patients with treatment-resistant mood or psychotic disorders, suggesting it can be safely implemented in clinical settings.

Preliminary results indicate that LAP-ST may reduce cognitive side effects compared to standard ECT while maintaining similar efficacy for treating depressive and psychotic symptoms, although further research with larger sample sizes is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Feasibility, safety, and preliminary efficacy of Low Amplitude Seizure Therapy (LAP-ST): A proof of concept clinical trial in man. Youssef, NA., Sidhom, E.[2022]

In a study of 40 patients with major depression, those receiving suprathreshold right unilateral ultrabrief-pulse ECT at a lower frequency of 40 Hz showed significantly greater improvement in depression scores compared to those treated at 100 Hz after 9 sessions.

Both frequency groups did not show significant differences in verbal and working memory, suggesting that the lower frequency ECT may be more effective without increasing cognitive side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stimulus pulse-frequency-dependent efficacy and cognitive adverse effects of ultrabrief-pulse electroconvulsive therapy in patients with major depression. Roepke, S., Luborzewski, A., Schindler, F., et al.[2012]

In a study of 1793 patients receiving their first course of ECT, 65.6% were treated exclusively with right unilateral ultrabrief pulse (RUL-UBP) ECT, indicating its widespread use and potential as a primary treatment method.

The mean dose of RUL-UBP ECT increased significantly from 7.6 times the seizure threshold at the second treatment to 14.3 times by the twelfth treatment, suggesting that while RUL-UBP is effective, adjustments in dosing may be necessary as treatment progresses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Rate of continuing acute course treatment using right unilateral ultrabrief pulse electroconvulsive therapy at a large academic medical center. Luccarelli, J., McCoy, TH., Shannon, AP., et al.[2022]

In a small study of three adults with ultrarefractory epilepsy, the dopaminergic agent Madopar showed promise by reducing or even eliminating tonic-clonic seizures in two patients after they had failed multiple antiepileptic drugs.

However, Madopar may worsen absence seizures in some cases, indicating that while it could be a potential treatment option, further research through randomized controlled trials is necessary to confirm its safety and efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjunctive Madopar for ultrarefractory epilepsy? Preliminary observations. Hodoba, D., Santic, AM., Schmidt, D.[2014]

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]

Antiepileptic drugs (AEDs) effectively suppress seizures but do not change the underlying disease process and can have side effects, including teratogenic risks, making their long-term use challenging.

For treating epilepsy, specific AEDs like oxcarbazepine, carbamazepine, and lamotrigine are recommended based on patient age and type of seizures, with treatment tailored to individual needs, especially for women of childbearing age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treating epilepsy across its different stages. Beghi, E.[2021]

In two cases of patients experiencing prolonged seizures during electroconvulsive therapy (ECT), treatment was safely continued using right unilateral ECT at a higher suprathreshold dose, resulting in no further seizures and significant clinical improvement.

The use of ultrabrief right unilateral ECT appears to reduce cognitive side effects while allowing for effective treatment, suggesting that prolonged seizures should not automatically halt ECT therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Selecting right unilateral placement to facilitate continuation of electroconvulsive therapy following prolonged seizures. Goh, SE., Tor, PC.[2021]

Recent studies suggest that monotherapy, particularly with valproate, can provide equal or better seizure control compared to polypharmacy in epilepsy management, reducing the risk of adverse reactions and improving patient compliance.

Valproate is shown to be at least as effective as other common anticonvulsants like phenytoin and carbamazepine for treating both generalized and partial seizures, indicating it is a strong option for monotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Valproate monotherapy in the management of generalized and partial seizures. Chadwick, DW.[2019]

Citations

1. afsp.org afsp.org/grant/efficacy-of-low-amplitude-pulse-seizure-therapy-lap-st-versus-standard-ultra-brie

Efficacy of Low Amplitude Pulse Seizure Therapy (LAP-ST) ... We will also examine if RUL LAP-ST will improve suicidal ideations faster than ECT (secondary outcome). Sample: Thirty male and female patients with SI and ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC6562950/

A Pilot Double-Blinded Randomized Clinical Trial Conclusions: LAP-ST has larger effect size and speed of remission of suicidality compared to standard RUL ECT. Future studies are warranted for ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT02583490

NCT02583490 | Low Pulse Amplitude Focal ECT (LAP Study) Magnitude of Reduction and Speed of Remission of Suicidality for Low Amplitude Seizure Therapy (LAP-ST) Compared to Standard Right Unilateral ...

4. trialx.com trialx.com/clinical-trials/listings/320577/low-amplitude-pulse-seizure-therapy-versus-standard-ultra-brief-right-unilateral-electroconvulsive-therapy/

Low Amplitude Pulse Seizure Therapy Versus Standard ... ECT has both research support (mainly secondary analysis) and clinical evidence of a beneficial effect in remission of suicidality, as well as ...

5. withpower.com withpower.com/trial/phase-2-and-3-suicidal-ideation-6-2024-08086

Low Amplitude Pulse Seizure Therapy for Suicidal Thoughts Research shows that Low Amplitude Pulse Seizure Therapy (LAP-ST) can reduce suicidal thoughts more quickly and effectively than standard electroconvulsive ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7763063/

Double-Blinded Randomized Pilot Clinical Trial Comparing ... The objectives of this study were to (1) examine the CSE of Low Amplitude Seizure Therapy (LAP-ST) at 0.5 A compared to Ultra-brief Right ...