Nonconvulsive Electrotherapy: a Proof-of-concept Trial

May 25, 2023 updated by: Joe Smith, University of Maryland, College Park

This study involves pilot testing of a modified version of a proven treatment for mental illness. The treatment, electroconvulsive therapy (ECT) is used to treat more than 100,000 Americans yearly. ECT is the most effective treatment for major depression, a disorder that affects approximately 5 to 8 percent of the adult US population yearly. It is also an effective treatment for mania and mixed mood states associated with bipolar disorder and schizoaffective disorder.

The aim of ECT is to induce a seizure, which is thought to be responsible for both its therapeutic and its adverse cognitive effects. The proposed modification consists of reducing the ECT electrical stimulus dose below the amount necessary to induce seizures so that adverse cognitive effects, such as confusion and memory problems, are minimized.

The investigators intend to determine whether ECT-related cognitive impairment can be reduced without diminishing the therapeutic effect of ECT. In addition to distressing patients, ECT-related cognitive impairment has significant public health consequences. These include increased morbidity and mortality among severely ill individuals who refuse ECT due to concern over its adverse cognitive effects as well as increased falls among the elderly receiving ECT. Elderly patients are far more likely to receive ECT and are also more vulnerable to ECT-related cognitive impairment. They often require hospitalization for ECT and a longer hospital stay with greater spacing of treatments to minimize adverse cognitive effects.

The hypothesis driving this research is that electrical brain stimulation applied in the same manner as standard ECT, but at a lower dose, can have therapeutic effects and fewer adverse cognitive effects without inducing seizures. This hypothesis is based on the following: 1) the investigators clinical experience of patients who have improved with ECT despite having only one or no seizure, 2) animal studies showing that electrical brain stimulation can induce antidepressant like effects in animals without inducing seizures, 3) reports from the 1950s that "subconvulsive" and "nonconvulsive" electrotherapy was effective for some patients, and 4) the recent approval by the US Food and Drug Administration of the use of transcranial magnetic stimulation --a technique that uses a magnet to induce an electrical current in the brain without inducing seizures--for treatment of medication resistant major depression.

The primary aim of the research is to conduct a proof of concept, open trial investigating the therapeutic efficacy and safety of nonconvulsive electrotherapy (NET). The investigators plan to enroll 16 subjects, which is the minimum number of subjects needed to show that the therapeutic effect of NET is better than would be expected of placebo. If the investigators show that the therapeutic effect of NET exceeds that expected of placebo and does not induce significant cognitive impairment, then the investigators will go on to propose a blind, randomized, controlled clinical trial that more definitively tests the investigators' hypothesis. The investigators would use the information gathered from the pilot trial to estimate the number of subjects needed to definitively test the efficacy and safety of NET.

The secondary aim of the study is to find out whether NET affects blood levels of brain-derived neurotrophic factor (BDNF). BDNF is a substance that is important to the nervous system and may be related to how treatments like ECT or possibly NET improve symptoms. The investigators would draw a blood sample before and after NET treatment to assess this.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

13

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  1. Men and women, aged 18 years and older meeting structured clinical interview for the DSM IV (SCID) criteria for unipolar major depressive disorder, bipolar disorder, or schizoaffective disorder.
  2. Subjects of child-bearing potential must agree to have a pregnancy test prior to enrollment and agree to use a reliable method of birth-control during the study.
  3. Willingness and ability to provide informed consent as determined by satisfactorily completing the study-specific Evaluation to Sign Consent Form Test.
  4. Baseline score ≥ 16 on the 21-item version of the Hamilton Depression Rating Scale (HAMD-21) for unipolar depression, the Bipolar Depression Rating Scale (BDRS) for bipolar depression, or the Young Mania rating scale (YMRS) for mania.
  5. Willingness to allow the Principal Investigator to discuss study participation with treating psychiatrist
  6. Taking the same regimen of psychiatric medications with no changes for at least one month prior to NET treatment and willingness to not have any medication changes during NET treatment.
  7. Currently an outpatient.
  8. History of or currently refusing ECT due to experience of or anticipation of adverse effects.

Exclusion Criteria:

  1. Pregnancy.
  2. Use of any investigational drugs within 30 days of baseline or at any time during the study.
  3. Ongoing substance abuse or dependence.
  4. Current suicidal ideas.
  5. Presence of any condition that would contraindicate ECT or bifrontal electrode placement.
  6. Medical or neurologic condition etiologically related to mood disorder.
  7. History of coronary artery disease or cardiac arrhythmia.
  8. History of serious, potentially life-threatening reaction to anesthesia.
  9. For individuals who need to have brain imaging, presence of metal in the body that would make a head MRI unsafe.
  10. For individuals who need to have brain imaging, history of claustrophobia or anxiety associated with previous MRI.
  11. Allergy or adverse reaction to methohexital or succinylcholine.
  12. Epilepsy or seizure disorder.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nonconvulsive electrotherapy
Open label single arm study of nonconvulsive electrotherapy
Device: Nonconvulsive electrotherapy
An electrical stimulus will be given as in electroconvulsive therapy (ECT)using bifrontal electrode placement and a Thymatron System IV device; however, the device will be set at a lower energy level that is 12.5%(1/8) of the expected energy needed to induce a seizure rather than at an energy level that is at or above the seizure threshold.
Other Names:
  • Thymatron System IV device made by Somatics, LLC.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Score on the 17-item Hamilton Depression Rating Scale
Time Frame: Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
Score range is 0 to 54 points. The higher the score, the more depressed symptoms.
Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Score on Mini-mental State Exam
Time Frame: Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
Score range is 0 to 30 points. The higher the score, the better the cognition. So a higher score means less cognitive impairment.
Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
Change in Score on the Autobiographical Memory Inventory Short Form (AMI-S)
Time Frame: Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
The Autobiographical Memory Inventory Short Form (AMI-S ) assesses effects on retrograde memory for autobiographical information including information related to a family member, recent travel, events of last New Year's eve, events of last birthday, employment information, and events of last non-psychiatric illness and its treatment. Subjects responded to specific questions regarding these topics before and after their course of NET treatment. Subjects were scored based on the percent of responses post-NET treatment that correctly matched their responses prior to NET treatment. The score range is 0 to 100%. The higher the percent, the less impaired is the autobiographical memory.
Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
Change in Brain-derived Neurotrophic Factor (BDNF) Blood Level
Time Frame: Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
Change in plasma level of BDNF in pg/ml pre and post NET treatment course.
Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, College Park

Collaborators

Brain & Behavior Research Foundation

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2010

Primary Completion (Actual)

March 1, 2014

Study Completion (Actual)

April 1, 2014

Study Registration Dates

First Submitted

February 8, 2010

First Submitted That Met QC Criteria

February 8, 2010

First Posted (Estimated)

February 9, 2010

Study Record Updates

Last Update Posted (Actual)

June 23, 2023

Last Update Submitted That Met QC Criteria

May 25, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HP-00040324

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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