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Title: Safety and Feasibility of Individualized Low Amplitude Seizure Therapy (iLAST)

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ClinicalTrials.gov Identifier: NCT03895658
Recruitment Status : Recruiting
First Posted : March 29, 2019
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) )

Brief Summary:

Background:

Electroconvulsive therapy (ECT) is used to treat people with severe depression. During ECT, the brain is given electric pulses that cause a seizure. Although it is effective, it can cause side effects, including memory loss. Researchers want to study a new way to give ECT called iLAST.

Objective:

To see if iLAST is safe and feasible in treating depression.

Eligibility:

People ages 22 70 years old who have major depressive disorder and are eligible for ECT

Design:

Participants will be screened under protocol 01-M-0254. This includes:

Medical and psychiatric history and exam

Blood and urine tests

Participants will be inpatients at the Clinical Center. They study has 3 phases and will last up to 20 weeks.

Phase I will last 1 week. It includes:

MRI: Participants will lie in a scanner that takes pictures of the body

MEG: A cone over the participant s head will record brain activity.

TMS: A wire coil placed on the participant s scalp will produce an electrical current to affect brain activity.

SEP: An electrode on the participant s wrist will give a small electrical shock to test nerve function.

Phase II will last 2 and a half weeks. It includes:

Seven sessions of iLAST under general anesthesia. Participants may also get standard ECT.

EEG: A small electrode placed on the participant s scalp will record brain waves.

Interviews about mood, symptoms, and side effects. Participants facial expressions may be video recorded.

TMS

Phase III will last at least 1 week. It will include:

MRI

EEG

TMS

MEG

Standard ECT if needed. Participants will have sessions every other day, 3 times a week.

Sponsoring Institution: National Institute of Mental Health

...


Condition or disease Intervention/treatment Phase
Unipolar Depression Device: Multichannel Stimulation Interface Phase 1

Detailed Description:

The primary aim of the current protocol is to evaluate the safety and feasibility of iLAST in 10 adults with major depressive episode (unipolar) eligible for ECT. We hypothesize that both iLAST will result in superior neurocognitive outcomes than conventional ECT. In addition, we will evaluate the feasibility of alternative methods to individualize the pulse amplitude. The approach to individualizing pulse amplitude is to apply trains of pulses of increasing amplitude until a seizure is induced. To be practical in the clinical setting, the motor threshold (MT) procedure will be completed rapidly to minimize time under anesthesia. To this end, we will evaluate a rapid- estimation motor thresholding algorithm under anesthesia. This will allow us to determine the relationships among measured amplitude-titrated seizure threshold (ST), measured MT, and simulated MT derived from electric field modeling. Our hypothesis is that both measured and simulated MT are correlated with STa, thus providing a clinically useful predictor of current amplitude necessary to perform seizure therapy under the time-constraints of anesthesia.

Study Population

The study will consist of 10 individuals between 22 and 70 years old, with a major depressive disorder.

Study Design

This is a within-subject safety and feasibility study that comprises three phases. Phase I includes medication taper (as clinically indicated), and baseline assessments.

In Phase II, patients will receive the 7 ultrabrief pulse width (0.3 ms) seizure therapy conditions. As treatments will be delivered on a 3 per week schedule.

On each experimental condition day, patients will undergo a number of procedures to assess clinical status and safety. Post procedure acute battery assessments will include: a) side effect questionnaire, b) neurocognitive battery, and c) neuroplasticity battery.

In Phase III, patients will be offered routine clinical management consisting of a conventional ECT course (typically 6 12 treatments) based on clinical need. Patients will receive pre- and post- course measures including: clinical rating scales, neurocognitive testing, neuroimaging, and a neuroplasticity battery.

Patients will also receive optional TMS EEG and ictal EEG recording at the 2nd, 8th or final treatment.

Outcome Measures

Primary Outcome measures: successful seizure induction as measured by topographical EEG and motor manifestations, vital signs, ECG, subjective side effect scale, and adverse events/significant adverse events.

Secondary Outcome measures: Neurocognitive battery known to be sensitive to the cognitive effects of ECT, with alternative versions to avoid practice effects; and, Amplitude-titrated seizure threshold (STa), measured electrical MT, and simulated MT derived from realistic head modeling.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Safety and Feasibility of Individualized Low Amplitude Seizure Therapy (iLAST)
Estimated Study Start Date : October 18, 2019
Estimated Primary Completion Date : December 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Seizures

Arm Intervention/treatment
Experimental: 1
This is a first-in-human study of safety and feasibility of a new approach to electroconvulsive therapy (ECT): individualized low amplitude seizure therapy. It uses high definition multielectrode array, coupled current amplitude titration to control the focal of seizure induction and individualize dosing. We aim to have 10 completers, between 21 and 70 years of age, with a current major depressive disorder in the context of unipolar major depression disorder eligible for ECT. The within-subject experiment comprises three phases. Phase I includes informed consent, screening, medication taper, and baseline clinical and neuroimaging assessments. Phase II, each patient will receive 7 experimental ECT configurations using the multielectrode array targeted to different brain regions. Finally, patients will be offered routine clinical ECT in Phase III.
Device: Multichannel Stimulation Interface
Multichannel Stimulation Interface

Experimental: 2
Each patient will receive 7 experimental ECT configurations using the multielectrode array targeted to different brain regions.
Device: Multichannel Stimulation Interface
Multichannel Stimulation Interface

No Intervention: 3
Patients will be offered routine clinical ECT in Phase III.



Primary Outcome Measures :
  1. Successful seizure induction as measured by topographical EEG and motor manifestations, vital signs, ECG, subjective side effect scale, and adverse events/significant adverse events [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. Neurocognitive battery known to be sensitive to the cognitive effects of ECT, with alternative versions to avoid practice effects; and, Amplitude- titrated seizure threshold (STa), measured electrical motor threshold (MT), and simulated MT [ Time Frame: 2 years ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   22 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria
  • INCLUSION CRITERIA:
  • Male and female, 22 70 years old
  • Use of effective method of birth control for women of childbearing capacity. Women who are able to get pregnant must be willing to use at least one form of effective birth control during the entire period of study participation (or until last clinical labs and rating) and have a negative pregnancy test at screening.
  • DSM-5 diagnosis of major depressive disorder, confirmed by the MINI
  • Eligible for ECT, including patients receiving maintenance ECT
  • Each subject must have a level of understanding sufficient to agree to all required tests and examinations and sign an informed consent document
  • Subjects are willing and able to adhere to the intensive treatment schedule and all required study procedures

EXCLUSION CRITERIA:

  • Pregnant or nursing women or women who plan to become pregnant.
  • Current or recent (within the past 6 months) substance abuse or dependence (excluding nicotine and caffeine)
  • Current serious medical illness judged to be clinically significant, such as high blood pressure, diabetes, heart or lung disease
  • History of seizure except those therapeutically induced by ECT (childhood febrile seizures are acceptable and these subjects may be included in the study), history of epilepsy in self or first degree relatives, stroke, brain surgery, concussion resulted in loss of consciousness or hospitalization, cranial metal implants, known structural brain lesion, devices that may be affected by TMS or MRI (pacemaker, medication pump, cochlear implant, implanted brain stimulator, vagus nerve stimulator)
  • Diagnosed with the following conditions (current unless otherwise stated):

    • Any other current primary Axis I mood, anxiety, or psychotic disorder
    • Depression secondary to a general medical condition, or substance-induced
    • Psychotic disorder (lifetime), including schizoaffective disorder, or major depression with psychotic features in the current episode
    • Eating disorder (current or within the past year)
    • Obsessive compulsive disorder (current or within the past year)
    • Post-traumatic stress disorder (current or within the past year)
    • ADHD (currently being treated)
    • Subjects meeting criteria based upon DSM-5 criteria, which in the judgment of the Investigator, may hinder the subjects in completing the procedures required by the study protocol
    • Actively suicidal
  • Increased risk of seizure for any reason, including prior diagnosis of increased intracranial pressure (such as after large infarctions or trauma), or currently taking medication that lowers the seizure threshold
  • Subjects with a clinically defined neurological disorder including, but not limited to:

    • Any condition likely to be associated with increased intracranial pressure
    • Space occupying brain lesion
    • History of stroke
    • Transient ischemic attack within two years
    • Cerebral aneurysm
    • Dementia
    • Mini Mental Status Exam (MMSE) score < 24
    • Parkinson s disease
    • Huntington s disease
    • Multiple sclerosis
  • Subjects with any of the following treatment histories:

    • Failure to respond to TMS or ECT treatment (i.e., consistent with ATHF confidence level 3 or higher) in this or any previous episode
    • Lifetime history of treatment with Deep Brain Stimulation or Vagus Nerve Stimulation
    • Use of any investigational drug or device within 4 weeks of the screening
  • MRI contraindications (any metal in the body, claustrophobia, etc.)
  • Current visual, auditory, or motor impairment that compromises ability to complete evaluations
  • Positive HIV test
  • NIMH employees and staff and their immediate family members will be excluded from the study per NIMH policy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03895658


Contacts
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Contact: Zhi-De Deng, Ph.D. (301) 594-0387 zhi-de.deng@nih.gov

Locations
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United States, Maryland
National Institutes of Health Clinical Center Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact Office of Patient Recruitment (OPR)    800-411-1222 ext TTY8664111010    prpl@cc.nih.gov   
Sponsors and Collaborators
National Institute of Mental Health (NIMH)
Investigators
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Principal Investigator: Sarah H Lisanby, M.D. National Institute of Mental Health (NIMH)

Additional Information:
Publications:
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Responsible Party: National Institute of Mental Health (NIMH)
ClinicalTrials.gov Identifier: NCT03895658     History of Changes
Other Study ID Numbers: 190073
19-M-0073
First Posted: March 29, 2019    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: March 20, 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by National Institutes of Health Clinical Center (CC) ( National Institute of Mental Health (NIMH) ):
Brain Stimulation
Neurocognitive
Major Depressive Disorder (MDD)
Additional relevant MeSH terms:
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Seizures
Depressive Disorder
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Mood Disorders
Mental Disorders