Nonconvulsive Electrotherapy: a Proof-of-concept Trial
|ClinicalTrials.gov Identifier: NCT01065597|
Recruitment Status : Completed
First Posted : February 9, 2010
Results First Posted : August 10, 2015
Last Update Posted : August 28, 2015
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.
|Condition or disease||Intervention/treatment||Phase|
|Depressive Disorder Bipolar Disorder Schizoaffective Disorder||Device: Nonconvulsive electrotherapy||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||13 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Nonconvulsive Electrotherapy: a Proof-of-concept Trial|
|Study Start Date :||May 2010|
|Actual Primary Completion Date :||March 2014|
|Actual Study Completion Date :||April 2014|
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 Name: Thymatron System IV device made by Somatics, LLC.
- 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.
- 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.
- 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.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01065597
|United States, Maryland|
|University of Maryland Medical Center|
|Baltimore, Maryland, United States, 21201|