Optimizing Stimulation Parameters for Electroconvulsive Therapy (PRESTO)

Parameter Refinement for ECT Stimulation and Titration Optimization

The goal of this clinical trial is to improve how electroconvulsive therapy (ECT) stimulation settings are chosen. Researchers will use real-time brain monitoring to measure both seizures and a recently identified brain event called cortical spreading depolarization (CSD).

The main questions it aims to answer are:

What is the best way to increase ECT stimulation settings? How do different pulse settings affect the brain's response? Can certain settings produce CSD without causing a seizure?

Participants already receiving ECT as part of their care will take part. They will be assigned to one of two groups:

Index ECT group: Participants starting ECT will receive different standard titration approaches.

Maintenance ECT group: Participants receiving ongoing ECT will undergo a brief, low-dose stimulation test before treatment.

All participants will be monitored using brain physiology (EEG and blood flow) and symptom scales during treatment.

Study Overview

• Status: Not yet recruiting
• Conditions: Catatonia; Depression - Major Depressive Disorder
• Intervention / Treatment: Procedure: Electroconvulsive Therapy

Detailed Description

This is an exploratory, single-center open-label clinical trial at Pennsylvania Hospital (PAH) intended to optimize stimulation settings for electroconvulsive therapy (ECT), guided by real-time monitoring of both seizure and a recently discovered postictal event: cortical spreading depolarization (CSD). We will address three key questions: 1. What is the best strategy for up-titrating settings for ECT?; 2. How do individual pulse parameters impact brain evoked response?; 3. Are there stimulation settings that directly induce CSD waves without seizure?

This study will take place in the context of routine treatments for patients already consenting to receive ECT for a wide range of clinical indications. Patients will be enrolled in one of two arms:

1. Index Titration Arm: Patients coming in for initial index ECT courses (acute phase) will be randomized to one of several stimulation parameter titration tables while receiving otherwise routine ECT care.
2. Maintenance Arm: In clinically stable patients receiving monthly maintenance ECT, a sub-convulsive stimulation settings ramp will be performed under anesthesia immediately preceding their regular ECT treatment.

All patients being treated with ECT at PAH are eligible for this study. Outcomes will include non-invasive monitoring of brain hemodynamics and EEG as well as clinical symptom scales.

• Study Type: Interventional
• Enrollment (Estimated): 64
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Zachary Rosenthal, MD PhD; Phone Number: 19738976511; Email: Zachary.Rosenthal@pennmedicine.upenn.edu
• Study Contact Backup: Name: Mario Cristancho, MD; Email: marioc@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19146
      • Pennsylvania Hospital
      • Contact: Zachary Rosenthal; Phone Number: 9738976511; Email: Zachary.Rosenthal@pennmedicine.upenn.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Any patients being treated with electroconvulsive therapy at Pennsylvania Hospital who are willing and able to participate are eligible to be subjects in this study.

Exclusion Criteria:

1. They are unwilling or unable to consent first to the SWEET COMBO protocol for optical monitoring during ECT
2. Clinically significant psychiatric comorbidity as determined by clinical interview and in the opinion of the Investigator and clinical team would alter the risk/benefit of the study
3. History of poor response to ECT treatment in the opinion of the Investigator and clinical team that would alter the risk/benefit of the study

4. Presence of any disease, medical condition or physical condition that, in the opinion of the Investigator, may compromise, interfere with, limit, affect or reduce the:

   1. subject's ability to participate safely in the study
   2. integrity of the data or
   3. subject's ability to complete the full duration of the study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Index: Standard titration table; Patients are treated with ECT using titration table 1 (alternating increases in frequency and duration)	Procedure: Electroconvulsive Therapy; Electrical stimulation under anesthesia
Experimental: Index: Frequency-then-duration; ECT provided using Table 2, frequency uptitration followed by duration uptitration	Procedure: Electroconvulsive Therapy; Electrical stimulation under anesthesia
Experimental: Index: Duration then Frequency; ECT provided using Table 3, duration titration then frequency titration	Procedure: Electroconvulsive Therapy; Electrical stimulation under anesthesia
Other: Maintenance; Internal cross-over arm in which patients undergo 8 sessions using 8 randomized sub-convulsive stimulation protocols	Procedure: Electroconvulsive Therapy; Electrical stimulation under anesthesia

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain hemodynamics	Functional near infrared spectroscopy imaging will be performed during each ECT treatment, from which we will extract oxy- and deoxyhemoglobin concentrations (in mM) over time.	Periprocedural (10-20 minutes per ECT session). Assessed repeatedly over approximately 12 ECT sessions for index arm patients (3 times/week for 4-6 weeks), or for 8 sessions (once a month for 8 months) in the maintenance arm.
Electroencephalography - Seizure Duration	Bilateral EEG over FP1 and FP2 zones, from which we will compute seizure duration (in seconds)	Periprocedural (10-20 minutes per ECT session). Assessed repeatedly over approximately 12 ECT sessions for index arm patients (3 times/week for 4-6 weeks), or for 8 sessions (once a month for 8 months) in the maintenance arm.
Electroencephalography - theta band power	Bilateral EEG over FP1 and FP2 zones, from which we will compute theta band power (in dB)	Periprocedural (10-20 minutes per ECT session). Assessed repeatedly over approximately 12 ECT sessions for index arm patients (3 times/week for 4-6 weeks), or for 8 sessions (once a month for 8 months) in the maintenance arm.
Electroencephalography - Brain Symmetry Index	Bilateral EEG over FP1 and FP2 zones, from which we will compute brain symmetry index (unitless)	Periprocedural (10-20 minutes per ECT session). Assessed repeatedly over approximately 12 ECT sessions for index arm patients (3 times/week for 4-6 weeks), or for 8 sessions (once a month for 8 months) in the maintenance arm.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quick Inventory of Depression Self-Report	Depression symptom scale filled out by patient. Unitless, ranging from 0-27.	Administered pre-procedurally at baseline and once weekly for index arm patients (for 4-6 weeks), or once monthly (for 8 months) in maintenance arm patients.
Bush Francis Catatonia Rating Scale	Catatonia rating scale conducted by clinical team. Unitless, ranging from 0-69.	Administered pre-procedurally at baseline and prior to every ECT treatment for index arm patients (12 treatments, 3 times weekly for for 4-6 weeks), or once monthly (for 8 months) in maintenance arm patients.
Single Letter Fluency	Test of verbal fluency. Unit is number of words starting with a given letter provided in a one minute period.	Administered pre-procedurally at baseline and prior to every ECT treatment for index arm patients (12 treatments, 3 times weekly for for 4-6 weeks), or once monthly (for 8 months) in maintenance arm patients.
3 word registration and recall	Test of short term memory. Unit is number (out of 3) words registered and repeated back at 0 minutes, and the same at 3 minutes delay.	Administered pre-procedurally at baseline and prior to every ECT treatment for index arm patients (12 treatments, 3 times weekly for for 4-6 weeks), or once monthly (for 8 months) in maintenance arm patients.
Psychotic Depression Assessment Scale (PDAS)	Psychosis rating scale for patients with psychosis, to be administered by clinical team. Unitless, ranging from 0-44.	Administered pre-procedurally at baseline and once weekly for index arm patients (for 4-6 weeks), or once monthly (for 8 months) in maintenance arm patients
Clinical Global Impressions Scale for Severity and Improvement	To be determined by clinical team. Unitless, ranging from 0-7.	Administered pre-procedurally at baseline and prior to every ECT treatment for index arm patients (12 treatments, 3 times weekly for for 4-6 weeks), or once monthly (for 8 months) in maintenance arm patients.

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Estimated): July 1, 2026
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: March 25, 2026
• First Submitted That Met QC Criteria: April 23, 2026
• First Posted (Actual): May 1, 2026

Study Record Updates

• Last Update Posted (Actual): May 1, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: electroconvulsive therapy
• Additional Relevant MeSH Terms: Neurologic Manifestations; Nervous System Diseases; Behavioral Symptoms; Neurobehavioral Manifestations; Pathological Conditions, Signs and Symptoms; Behavior; Signs and Symptoms; Catatonia; Behavioral Disciplines and Activities; Convulsive Therapy; Psychiatric Somatic Therapies; Electroshock; Psychological Techniques; Electroconvulsive Therapy
• Other Study ID Numbers: 26-6396

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No