Depressive DisorderPhase 1NCT01065597
Nonconvulsive Electrotherapy: a Proof-of-concept Trial
A Phase 1 study testing Nonconvulsive electrotherapy in people with Depressive Disorder and Bipolar Disorder, run by University of Maryland, College Park at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Depressive Disorder, Bipolar Disorder, Schizoaffective Disorder
- What is being tested?
- Nonconvulsive electrotherapy
- Type of treatment
- Injection or infusion, Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 1 siteUnited States
- Study dates
- May 2010to Apr 2014
- Phase
- Phase 1
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
- 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.
- Willingness and ability to provide informed consent as determined by satisfactorily completing the study-specific Evaluation to Sign Consent Form Test.
- 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.
- Willingness to allow the Principal Investigator to discuss study participation with treating psychiatrist
- 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.
- Currently an outpatient.
- History of or currently refusing ECT due to experience of or anticipation of adverse effects.
Who cannot join
- Pregnancy.
- Use of any investigational drugs within 30 days of baseline or at any time during the study.
- Ongoing substance abuse or dependence.
- Current suicidal ideas.
- Presence of any condition that would contraindicate ECT or bifrontal electrode placement.
- Medical or neurologic condition etiologically related to mood disorder.
Show all 12Show fewer
- History of coronary artery disease or cardiac arrhythmia.
- History of serious, potentially life-threatening reaction to anesthesia.
- For individuals who need to have brain imaging, presence of metal in the body that would make a head MRI unsafe.
- For individuals who need to have brain imaging, history of claustrophobia or anxiety associated with previous MRI.
- Allergy or adverse reaction to methohexital or succinylcholine.
- Epilepsy or seizure disorder.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Medical Center
Baltimore, Maryland, 21201
About this study
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.
Read more
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.
- Being tested
- Nonconvulsive electrotherapy
- Keywords
- electroconvulsive therapy, seizure, nonconvulsive, subconvulsive, major depression, bipolar disorder
- Medical subject headings
- Depressive Disorder, Bipolar Disorder, Psychotic Disorders, Seizures, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nonconvulsive electrotherapyDevice
Also called Thymatron System IV device made by Somatics, LLC.
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.
| Study group | Role | What they receive |
|---|---|---|
| Nonconvulsive electrotherapy | Experimental | Open label single arm study of nonconvulsive electrotherapy Receives: Device: Nonconvulsive electrotherapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Score on the 17-item Hamilton Depression Rating Scale
Score range is 0 to 54 points. The higher the score, the more depressed symptoms.
Measured: Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
Secondary outcomes (3)
Change in Score on Mini-mental State Exam
Score range is 0 to 30 points. The higher the score, the better the cognition. So a higher score means less cognitive impairment.
Measured: 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)
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.
Measured: 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
Change in plasma level of BDNF in pg/ml pre and post NET treatment course.
Measured: Baseline and at the end of the NET treatment course 2-4 weeks later, depending on the number of NET treatments
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Feb 2010 (estimated)
- Study startMay 2010
- Primary completionMar 2014
- Study completionApr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Depressive DisorderStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, College Park
- Sponsor type
- University, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Responsible party
- Principal investigator, Joe Smith, University of Maryland, College Park
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01065597
- Sponsor's protocol ID
- HP-00040324
- Status last verified
- May 2023
- First submitted
- 8 Feb 2010
- Last updated
- 23 Jun 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Gersner R, Toth E, Isserles M, Zangen A. Site-specific antidepressant effects of repeated subconvulsive electrical stimulation: potential role of brain-derived neurotrophic factor. Biol Psychiatry. 2010 Jan 15;67(2):125-32. doi: 10.1016/j.biopsych.2009.09.015.
PubMed 19880094BERAN M, PERKINS JC, SCOLLON RW. Psychological studies on patients undergoing nonconvulsive electric-stimulation treatment. Am J Psychiatry. 1952 Nov;109(5):367-74. doi: 10.1176/ajp.109.5.367. No abstract available.
PubMed 12985996Regenold WT, Noorani RJ, Piez D, Patel P. Nonconvulsive Electrotherapy for Treatment Resistant Unipolar and Bipolar Major Depressive Disorder: A Proof-of-concept Trial. Brain Stimul. 2015 Sep-Oct;8(5):855-61. doi: 10.1016/j.brs.2015.06.011. Epub 2015 Jun 26.
PubMed 26187603
Study at a glance
From the registry record, last updated by the sponsor on 23 Jun 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Nonconvulsive Electrotherapy: a Proof-of-concept Trial
- ClinicalTrials.gov ID
- NCT01065597
- Acronym / sponsor ID
- HP-00040324
- Keywords
- electroconvulsive therapy, seizure, nonconvulsive, subconvulsive, major depression, bipolar disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 13 participants (actual)
- Lead sponsor
- University of Maryland, College ParkUniversity, hospital or other
- Collaborators
- Brain & Behavior Research Foundation
- Study start
- May 2010
- Primary completion
- Mar 2014 (actual)
- Study completion
- Apr 2014 (actual)
- First posted
- 9 Feb 2010 (estimated)
- Results
- Posted 10 Aug 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nonconvulsive electrotherapy | Experimental | Device: Nonconvulsive electrotherapyOpen label single arm study of nonconvulsive electrotherapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- 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.
- Willingness and ability to provide informed consent as determined by satisfactorily completing the study-specific Evaluation to Sign Consent Form Test.
- 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.
- Willingness to allow the Principal Investigator to discuss study participation with treating psychiatrist
Key exclusion criteria (12 listed)
- Pregnancy.
- Use of any investigational drugs within 30 days of baseline or at any time during the study.
- Ongoing substance abuse or dependence.
- Current suicidal ideas.
- Presence of any condition that would contraindicate ECT or bifrontal electrode placement.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nonconvulsive electrotherapyAlso: Thymatron System IV device made by Somatics, LLC.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. | Device | Nonconvulsive electrotherapy |
Primary outcome
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.
3 secondary outcomes
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
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
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
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jun 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19880094Gersner R, Toth E, Isserles M, Zangen A. Site-specific antidepressant effects of repeated subconvulsive electrical stimulation: potential role of brain-derived neurotrophic factor. Biol Psychiatry. 2010 Jan 15;67(2):125-32. doi: 10.1016/j.biopsych.2009.09.015.
- Background: PubMed 12985996BERAN M, PERKINS JC, SCOLLON RW. Psychological studies on patients undergoing nonconvulsive electric-stimulation treatment. Am J Psychiatry. 1952 Nov;109(5):367-74. doi: 10.1176/ajp.109.5.367. No abstract available.
- Derived from this study: PubMed 26187603Regenold WT, Noorani RJ, Piez D, Patel P. Nonconvulsive Electrotherapy for Treatment Resistant Unipolar and Bipolar Major Depressive Disorder: A Proof-of-concept Trial. Brain Stimul. 2015 Sep-Oct;8(5):855-61. doi: 10.1016/j.brs.2015.06.011. Epub 2015 Jun 26.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Nonconvulsive electrotherapy in people with Depressive Disorder and Bipolar Disorder, run by University of Maryland, College Park at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jun 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01065597, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jun 2023; AzTrials last refreshed its copy on 31 Oct 2026.