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Mechanism of Action of tACS for the Treatment of MDD (GLADIATOR2)

Primary Purpose

Major Depressive Disorder, MDD

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
tACS
Sham tACS
Sponsored by
University of North Carolina, Chapel Hill
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Major Depressive Disorder focused on measuring tACS, Major Depressive Disorder, MDD, mood symptoms, sham

Eligibility Criteria

18 Years - 70 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Ages 18-70 years
  • DSM-IV diagnosis of MDD; unipolar, non-psychotic
  • Hamilton Rating Depression Rating Scale (HRDS-17) score >8
  • Low suicide risk as determined by a score of <3 on the Suicide Item on the HDRS-17 and based on additional information from the C-SSRS (no intent)
  • Capacity to understand all relevant risks and potential benefits of the study (informed consent)

Exclusion Criteria:

  • DSM-V diagnosis of moderate or severe alcohol use disorder (AUD) within the last 12 months.
  • DSM-V diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months.
  • Current axis I mood, or psychotic disorder other than major depressive disorder
  • Lifetime comorbid psychiatric bipolar or psychotic disorder
  • Eating disorder (current or within the past 6 months)
  • Obsessive-compulsive disorder (lifetime)
  • Post-traumatic stress disorder (PTSD, current or within the last 6 months)
  • Attention deficit hyperactivity disorder (ADHD, currently under treatment)
  • Current use of benzodiazepines or anti-epileptic drugs
  • Antidepressant drugs taken for less than 4 weeks (i.e., recently initiated)
  • Neurological disorders, including but not limited to history of seizures (except childhood febrile seizures and ECT-induced seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurysm.
  • Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation; comorbid neurological condition (i.e. seizure disorder, brain tumor)
  • History of traumatic brain injury that required subsequent cognitive rehabilitation, or cause cognitive sequelae.
  • Prior brain surgery and/or any brain devices/implants, including cochlear implants and aneurysm clips
  • Current pregnancy or lactation. If the ability to become pregnant exists, unwillingness to use appropriate birth control measures during study participation
  • Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study
  • Non-English speakers

Sites / Locations

  • UNC at Vilcom Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Sham Comparator

Arm Label

alpha Transcranial alternating current stimulation (tACS).

Sham stimulation

Arm Description

10 Hz tACS with a zero-to-peak amplitude of 1 mA for 40 minutes.

20 seconds of ramp-up, 40 seconds of 10 Hz tACS with zero-to-peak amplitude of 1 mA, and 20 seconds of ramp-down for a total of 80 seconds of stimulation.

Outcomes

Primary Outcome Measures

Change in the amplitude of left frontal alpha oscillations measured durin resting-state EEG recordings from baseline to day 5 of stimulation.
Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes. The difference between the baseline recording on the first day of stimulation is compared to the recording on the fifth day of the intervention prior to stimulation.
Change in the amplitude of left frontal alpha oscillations measured during resting-state EEG recordings from baseline to two-week follow-up of stimulation.
Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes. The difference between the baseline recording on the first day of stimulation is compared to the recording on the two-week follow-up after intervention.

Secondary Outcome Measures

Correlation between changes in the amplitude of left frontal alpha oscillations from baseline to day 5 of intervention and changes in symptoms of depression.
Correlation Coefficient (r) will be used to determine if there is a relationship between the change in Hamilton Depression Rating Scale (HDRS) scores from baseline to Day 5 and the two-week follow up and change in the amplitude of left frontal alpha oscillations before stimulation at baseline and Day 5 of stimulation. The HDRS is a clinician-rated measure of depression severity where higher scores indicate greater depression severity. To calculate the amplitude of left frontal alpha oscillations, Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes.
Correlation between changes in the amplitude of left frontal alpha oscillations from baseline to two-week follow-up and depression symptoms.
Correlation Coefficient (r) will be used to determine if there is a relationship between the change in Hamilton Depression Rating Scale (HDRS) scores from baseline, Day 5 and to two-week follow up and change in the amplitude of left frontal alpha oscillations before stimulation at baseline and Day 5 of stimulation. The HDRS is a clinician-rated measure of depression severity where higher scores indicate greater depression severity. To calculate the amplitude of left frontal alpha oscillations, Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes.
Correlation between changes in the amplitude of left frontal alpha oscillations and changes in symptoms of depression from baseline to two-week follow-up
Correlation Coefficient (r) will be used to determine if there is a relationship between the change in Hamilton Depression Rating Scale (HDRS) scores from baseline to Day 5 and two-week follow up and change in the amplitude of left frontal alpha oscillations before stimulation at baseline and two-week follow-up. The HDRS is a clinician-rated measure of depression severity where higher scores indicate greater depression severity. To calculate the amplitude of left frontal alpha oscillations, Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes.

Full Information

First Posted
June 10, 2019
Last Updated
June 6, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
Foundation of Hope, North Carolina
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1. Study Identification

Unique Protocol Identification Number
NCT03994081
Brief Title
Mechanism of Action of tACS for the Treatment of MDD
Acronym
GLADIATOR2
Official Title
Mechanism of Action for Transcranial Alternating Current (tACS) Stimulation for the Treatment of Major Depressive Disorder (MDD)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Completed
Study Start Date
June 9, 2021 (Actual)
Primary Completion Date
June 2, 2023 (Actual)
Study Completion Date
June 2, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
Foundation of Hope, North Carolina

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The purpose of this research study is to use a specific type of non-invasive brain stimulation known as transcranial alternating current stimulation (tACS) to determine its effects on brain activity (measured with EEG) and mood in patients with Major Depressive Disorder (MDD).
Detailed Description
The device used for non-invasive brain stimulation is investigational and has not been approved by the FDA, though it has been designated as a nonsignificant risk (NSR) device study by the FDA. Half of the participants will receive tACS and half will receive sham stimulation, an inactive control procedure for comparison use only. Participation in this study includes up to eight appointments, each one lasting from 30 minutes to four hours over the course of 3 weeks. The first two appointments will be remote interviews to determine eligibility. If the subjects qualify, the next five appointments will be scheduled as consecutive stimulation sessions in the Carolina Center for Neurostimulation at the Vilcom office. The follow-up appointment will be in our center two weeks after the completion of the stimulation sessions. We estimate the total time needed to complete study participation to be about 17 hours.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, MDD
Keywords
tACS, Major Depressive Disorder, MDD, mood symptoms, sham

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Using sham stimulation.
Allocation
Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
alpha Transcranial alternating current stimulation (tACS).
Arm Type
Experimental
Arm Description
10 Hz tACS with a zero-to-peak amplitude of 1 mA for 40 minutes.
Arm Title
Sham stimulation
Arm Type
Sham Comparator
Arm Description
20 seconds of ramp-up, 40 seconds of 10 Hz tACS with zero-to-peak amplitude of 1 mA, and 20 seconds of ramp-down for a total of 80 seconds of stimulation.
Intervention Type
Device
Intervention Name(s)
tACS
Intervention Description
XCSITE100
Intervention Type
Device
Intervention Name(s)
Sham tACS
Intervention Description
XCSITE100
Primary Outcome Measure Information:
Title
Change in the amplitude of left frontal alpha oscillations measured durin resting-state EEG recordings from baseline to day 5 of stimulation.
Description
Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes. The difference between the baseline recording on the first day of stimulation is compared to the recording on the fifth day of the intervention prior to stimulation.
Time Frame
Baseline, Day 5
Title
Change in the amplitude of left frontal alpha oscillations measured during resting-state EEG recordings from baseline to two-week follow-up of stimulation.
Description
Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes. The difference between the baseline recording on the first day of stimulation is compared to the recording on the two-week follow-up after intervention.
Time Frame
Baseline, two-week follow-up visit
Secondary Outcome Measure Information:
Title
Correlation between changes in the amplitude of left frontal alpha oscillations from baseline to day 5 of intervention and changes in symptoms of depression.
Description
Correlation Coefficient (r) will be used to determine if there is a relationship between the change in Hamilton Depression Rating Scale (HDRS) scores from baseline to Day 5 and the two-week follow up and change in the amplitude of left frontal alpha oscillations before stimulation at baseline and Day 5 of stimulation. The HDRS is a clinician-rated measure of depression severity where higher scores indicate greater depression severity. To calculate the amplitude of left frontal alpha oscillations, Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes.
Time Frame
Baseline, Day 5
Title
Correlation between changes in the amplitude of left frontal alpha oscillations from baseline to two-week follow-up and depression symptoms.
Description
Correlation Coefficient (r) will be used to determine if there is a relationship between the change in Hamilton Depression Rating Scale (HDRS) scores from baseline, Day 5 and to two-week follow up and change in the amplitude of left frontal alpha oscillations before stimulation at baseline and Day 5 of stimulation. The HDRS is a clinician-rated measure of depression severity where higher scores indicate greater depression severity. To calculate the amplitude of left frontal alpha oscillations, Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes.
Time Frame
Baseline, two-week follow-up visit
Title
Correlation between changes in the amplitude of left frontal alpha oscillations and changes in symptoms of depression from baseline to two-week follow-up
Description
Correlation Coefficient (r) will be used to determine if there is a relationship between the change in Hamilton Depression Rating Scale (HDRS) scores from baseline to Day 5 and two-week follow up and change in the amplitude of left frontal alpha oscillations before stimulation at baseline and two-week follow-up. The HDRS is a clinician-rated measure of depression severity where higher scores indicate greater depression severity. To calculate the amplitude of left frontal alpha oscillations, Fourier transform is applied to 2 second epochs of resting-state EEG data and averaged across epochs. The amplitude of alpha oscillations is calculated and averaged across left frontal electrodes.
Time Frame
Baseline, two-week follow-up visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Ages 18-70 years DSM-IV diagnosis of MDD; unipolar, non-psychotic Hamilton Rating Depression Rating Scale (HRDS-17) score >8 Low suicide risk as determined by a score of <3 on the Suicide Item on the HDRS-17 and based on additional information from the C-SSRS (no intent) Capacity to understand all relevant risks and potential benefits of the study (informed consent) Exclusion Criteria: DSM-V diagnosis of moderate or severe alcohol use disorder (AUD) within the last 12 months. DSM-V diagnosis of moderate to severe substance use disorder (excluding tobacco) within the last 12 months. Current axis I mood, or psychotic disorder other than major depressive disorder Lifetime comorbid psychiatric bipolar or psychotic disorder Eating disorder (current or within the past 6 months) Obsessive-compulsive disorder (lifetime) Post-traumatic stress disorder (PTSD, current or within the last 6 months) Change of ADHD medication within the last 4 weeks. Change of benzodiazepines or anti-epileptic medication within the last 4 weeks Antidepressant drugs taken for less than 4 weeks (i.e., recently initiated) Neurological disorders, including but not limited to history of seizures (except childhood febrile seizures and ECT-induced seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurysm. Medical or neurological illness (unstable cardiac disease, AIDS, malignancy, liver or renal impairment) or treatment for a medical disorder that could interfere with study participation; comorbid neurological condition (i.e. seizure disorder, brain tumor) History of traumatic brain injury that required subsequent cognitive rehabilitation, or cause cognitive sequelae. Prior brain surgery and/or any brain devices/implants, including cochlear implants and aneurysm clips Current pregnancy or lactation. If the ability to become pregnant exists, unwillingness to use appropriate birth control measures during study participation Anything that, in the opinion of the investigator, would place the participant at increased risk or preclude the participant's full compliance with or completion of the study Non-English speakers
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David Rubinow, MD
Organizational Affiliation
University of North Carolina at Chapel Hill - Department of Psychiatry
Official's Role
Principal Investigator
Facility Information:
Facility Name
UNC at Vilcom Center
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27514
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be shared upon request.
IPD Sharing Time Frame
Data will be available starting from 9 to 36 months following publication.
IPD Sharing Access Criteria
Deidentified individual data that supports the results will be shared beginning 9 to 36 months following publication provided the investigator who proposes to use the data has approval from an Institutional Review Board (IRB), Independent Ethics Committee (IEC), or Research Ethics Board (REB), as applicable, and executes a data use/sharing agreement with UNC.

Learn more about this trial

Mechanism of Action of tACS for the Treatment of MDD

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