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

• ClinicalTrials.gov Identifier: NCT03994081
• Recruitment Status: Recruiting
• First Posted: June 21, 2019
• Last Update Posted: May 17, 2022
• Sponsor: University of North Carolina, Chapel Hill
• Collaborator: Foundation of Hope, North Carolina
• Information provided by (Responsible Party): University of North Carolina, Chapel Hill

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).

Condition or disease	Intervention/treatment	Phase
Major Depressive Disorder; MDD	Device: tACS; Device: Sham tACS	Not Applicable

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 20 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Masking Description: Using sham stimulation.
• Primary Purpose: Basic Science
• Official Title: Mechanism of Action for Transcranial Alternating Current (tACS) Stimulation for the Treatment of Major Depressive Disorder (MDD)
• Actual Study Start Date: June 9, 2021
• Estimated Primary Completion Date: May 1, 2023
• Estimated Study Completion Date: June 1, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: alpha Transcranial alternating current stimulation (tACS).; 10 Hz tACS with a zero-to-peak amplitude of 1 mA for 40 minutes.	Device: tACS; XCSITE100
Sham Comparator: Sham stimulation; 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.	Device: Sham tACS; XCSITE100

Outcome Measures

Primary Outcome Measures :

1. Change in the amplitude of left frontal alpha oscillations measured durin resting-state EEG recordings from baseline to day 5 of stimulation. [ Time Frame: Baseline, Day 5 ]
   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.
2. Change in the amplitude of left frontal alpha oscillations measured during resting-state EEG recordings from baseline to two-week follow-up of stimulation. [ Time Frame: Baseline, two-week follow-up visit ]
   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 :

1. Correlation between changes in the amplitude of left frontal alpha oscillations from baseline to day 5 of intervention and changes in symptoms of depression. [ Time Frame: Baseline, Day 5 ]
   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.
2. Correlation between changes in the amplitude of left frontal alpha oscillations from baseline to two-week follow-up and depression symptoms. [ Time Frame: Baseline, two-week follow-up visit ]
   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.
3. Correlation between changes in the amplitude of left frontal alpha oscillations and changes in symptoms of depression from baseline to two-week follow-up [ Time Frame: Baseline, two-week follow-up visit ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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)
• 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

Contacts and Locations

Contacts

Contact: Tobias U Schwippel, MD; 984-974-6239; tobias_schwippel@unc.edu

Locations

United States, North Carolina

UNC at Vilcom Center; Recruiting

Chapel Hill, North Carolina, United States, 27514

Contact: Tobias U Schwippel, MD 984-974-6239 GLAD2study@unc.edu

Sponsors and Collaborators

University of North Carolina, Chapel Hill

Foundation of Hope, North Carolina

Investigators

• Principal Investigator: David Rubinow, MD; University of North Carolina at Chapel Hill - Department of Psychiatry

More Information

• Responsible Party: University of North Carolina, Chapel Hill
• ClinicalTrials.gov Identifier: NCT03994081
• Other Study ID Numbers: 20-1822
• First Posted: June 21, 2019
• Last Update Posted: May 17, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: IPD will be shared upon request.
• Supporting Materials: Study Protocol; Informed Consent Form (ICF); Analytic Code
• Time Frame: Data will be available starting from 9 to 36 months following publication.
• 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.

• 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

Keywords provided by University of North Carolina, Chapel Hill:

tACS; Major Depressive Disorder; MDD; mood symptoms; sham

Additional relevant MeSH terms:

Depressive Disorder; Depression; Depressive Disorder, Major; Mood Disorders; Mental Disorders; Behavioral Symptoms