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Investigating the Causal Role of Prefrontal Control in Decision-making in Patients With Anhedonia (DEBRA)

Primary Purpose

Major Depressive Disorder, Anhedonia

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus
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 transcranial Alternating Current Stimulation, Goal-directed behavior, Cross-frequency coupling, Reward-based decision-making

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Able to provide informed consent
  • Have normal to corrected vision
  • Willing to comply with all study procedures and be available for the duration of the study
  • Speak and understand English
  • Low suicide risk as determined by the Columbia Suicide Severity Rating Scale (C-SSRS), and by the Hamilton Depression Rating Scale (HAM-D; less than 3 for the suicidality item).
  • Negative pregnancy test for female participants
  • Patient Health Questionnaire (PHQ) with 9 items greater than or equal to 10 and a diagnosis of major depressive disorder on the Mini International Neuropsychiatric Interview (MINI)

Exclusion Criteria:

  • Attention deficit (hyperactivity) disorder (currently under treatment)
  • Neurological disorders and conditions, including, but not limited to: History of epilepsy, seizures (except childhood febrile seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurysm, brain tumors
  • Medical or neurological illness or treatment for a medical disorder that could interfere with study participation (e.g., unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment)
  • Prior brain surgery
  • Any brain devices/implants, including cochlear implants and aneurysm clips
  • History of current traumatic brain injury
  • (For females) Pregnant or breast feeding
  • 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
  • Diagnostic and Statistical Manual of Mental Disorders version 5 diagnosis of present moderate or severe substance use disorder or alcohol use disorder, and past severe substance use disorder or alcohol use disorder, or psychotic disorder within the last 12 months
  • Not taking medications for attention deficit (hyperactivity) disorder or benzodiazepines as these medications often produce specific EEG activity that may disrupt our interpretation of the findings
  • If major depressive disorder is experienced in episode, the participant must currently be within a depressive episode.
  • Contraindications for magnetic resonance imaging (MRI): ferrous metal inside the body, jewelry must be removable, pacemaker or cochlear implant.

Sites / Locations

  • University of North Carolina at Chapel Hill

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Sham Comparator

Arm Label

Delta-beta tACS

Theta-gamma tACS

Active-sham tACS

Arm Description

The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz).

This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz).

For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment.

Outcomes

Primary Outcome Measures

Percentage of trials that the participant chooses to perform the hard task
Goal-directed behavior will be calculated as the percentage of trials in which the participant decides to perform the most difficult effort exertion task in the Expenditure of Effort for Reward Task. The average for the four blocks prior to stimulation serve as a baseline and the eight blocks during stimulation will be calculated and the difference from baseline will be investigated.

Secondary Outcome Measures

Coupling strength between low-frequency prefrontal signals and high-frequency posterior signals
Phase-amplitude coupling strength is calculated between the phase of low-frequency activity in prefrontal electrodes and amplitude of high-frequency in posterior cortex. These signals are extracted from eyes-open resting-state periods after stimulation is turned off following each task block. Instantaneous phase and amplitude will be calculated by averaging electrodes in the regions, band-filtering to the specified range, and performing the Hilbert transform. Next, a hybrid signal is created using the high-frequency amplitude and low-frequency phase. Coupling strength is the magnitude of the average of this signal over time. Finally, coupling strength is normalized using a z-transformation with respect to a null distribution generated by randomly time-shifting the high-frequency time-series.

Full Information

First Posted
October 6, 2021
Last Updated
September 11, 2023
Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Mental Health (NIMH)
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1. Study Identification

Unique Protocol Identification Number
NCT05084924
Brief Title
Investigating the Causal Role of Prefrontal Control in Decision-making in Patients With Anhedonia
Acronym
DEBRA
Official Title
Causal Role of Delta-beta Coupling for Goal-directed Behavior in Anhedonia
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
November 2, 2021 (Actual)
Primary Completion Date
July 31, 2023 (Actual)
Study Completion Date
July 31, 2023 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of North Carolina, Chapel Hill
Collaborators
National Institute of Mental Health (NIMH)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Investigating whether delta-beta cross-frequency transcranial alternating current stimulation can increase goal-directed behavior in participants with major depressive disorder and elevated symptoms of anhedonia.
Detailed Description
The purpose of this clinical trial is to investigate the causal role that delta-beta coupling plays in goal-directed behavior in participants with major depressive disorder (MDD) and symptoms of anhedonia. The participants will perform a reward-based decision-making task. During the task, cross-frequency transcranial alternating current stimulation (tACS) will be delivered at delta-beta frequency, a control-frequency, or an active sham. Electroencephalography will be collected in intermittent resting-state periods. Structural and functional magnetic resonance imaging (MRI) will be collected during the resting-state and during performance of the task.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Major Depressive Disorder, Anhedonia
Keywords
transcranial Alternating Current Stimulation, Goal-directed behavior, Cross-frequency coupling, Reward-based decision-making

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
Participants are randomized into one of three arms of the study: delta-beta tACS, control tACS in theta-gamma, or active sham. Randomization is stratified by SHAPS level such that there are an equal number of participants that are high anhedonia (SHAPS > 33) and low anhedonia (SHAPS <=33).
Masking
ParticipantInvestigator
Masking Description
This study is designed to be double-blind. Participants and the researchers are unaware of each participant's assignment until the completion of all data collection. This is accomplished using randomization codes. Furthermore, this study utilizes an active sham stimulation. This means that the active sham condition includes some stimulation, mimicking the skin sensations associated with tACS. In a previously concluded trial, participants in the delta-beta tACS, theta-gamma tACS, and active sham groups responded similarly to the blinding questionnaire, indicating that the active sham stimulation successfully blinded the participants.
Allocation
Randomized
Enrollment
69 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Delta-beta tACS
Arm Type
Experimental
Arm Description
The study is investigating the use of transcranial alternating current stimulation (tACS). The stimulation is delivered at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. For the experimental arm, the tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz).
Arm Title
Theta-gamma tACS
Arm Type
Active Comparator
Arm Description
This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz).
Arm Title
Active-sham tACS
Arm Type
Sham Comparator
Arm Description
For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 10 seconds and then returns to baseline. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset of stimulation, assisting with blinding the participant's assignment.
Intervention Type
Device
Intervention Name(s)
Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus
Intervention Description
Stimulation will be delivered via the NeuroConn Direct Current Stimulator Plus, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Primary Outcome Measure Information:
Title
Percentage of trials that the participant chooses to perform the hard task
Description
Goal-directed behavior will be calculated as the percentage of trials in which the participant decides to perform the most difficult effort exertion task in the Expenditure of Effort for Reward Task. The average for the four blocks prior to stimulation serve as a baseline and the eight blocks during stimulation will be calculated and the difference from baseline will be investigated.
Time Frame
3 hours
Secondary Outcome Measure Information:
Title
Coupling strength between low-frequency prefrontal signals and high-frequency posterior signals
Description
Phase-amplitude coupling strength is calculated between the phase of low-frequency activity in prefrontal electrodes and amplitude of high-frequency in posterior cortex. These signals are extracted from eyes-open resting-state periods after stimulation is turned off following each task block. Instantaneous phase and amplitude will be calculated by averaging electrodes in the regions, band-filtering to the specified range, and performing the Hilbert transform. Next, a hybrid signal is created using the high-frequency amplitude and low-frequency phase. Coupling strength is the magnitude of the average of this signal over time. Finally, coupling strength is normalized using a z-transformation with respect to a null distribution generated by randomly time-shifting the high-frequency time-series.
Time Frame
3 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Able to provide informed consent Have normal to corrected vision Willing to comply with all study procedures and be available for the duration of the study Speak and understand English Low suicide risk as determined by the Columbia Suicide Severity Rating Scale (C-SSRS), and by the Hamilton Depression Rating Scale (HAM-D; less than 3 for the suicidality item). Negative pregnancy test for female participants Patient Health Questionnaire (PHQ) with 9 items greater than or equal to 10 and a diagnosis of major depressive disorder on the Mini International Neuropsychiatric Interview (MINI) Exclusion Criteria: Attention deficit (hyperactivity) disorder (currently under treatment) Neurological disorders and conditions, including, but not limited to: History of epilepsy, seizures (except childhood febrile seizures), dementia, history of stroke, Parkinson's disease, multiple sclerosis, cerebral aneurysm, brain tumors Medical or neurological illness or treatment for a medical disorder that could interfere with study participation (e.g., unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment) Prior brain surgery Any brain devices/implants, including cochlear implants and aneurysm clips History of current traumatic brain injury (For females) Pregnant or breast feeding 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 Diagnostic and Statistical Manual of Mental Disorders version 5 diagnosis of present moderate or severe substance use disorder or alcohol use disorder, and past severe substance use disorder or alcohol use disorder, or psychotic disorder within the last 12 months Not taking medications for attention deficit (hyperactivity) disorder or benzodiazepines as these medications often produce specific EEG activity that may disrupt our interpretation of the findings If major depressive disorder is experienced in episode, the participant must currently be within a depressive episode. Contraindications for magnetic resonance imaging (MRI): ferrous metal inside the body, jewelry must be removable, pacemaker or cochlear implant.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Flavio Frohlich
Organizational Affiliation
University of North Carolina, Chapel Hill
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of North Carolina at Chapel Hill
City
Chapel Hill
State/Province
North Carolina
ZIP/Postal Code
27599
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
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.
IPD Sharing Time Frame
from 9 to 36 months following publication
IPD Sharing Access Criteria
Deidentified individual data that supports the results will be shared provided the investigator who proposes to use the data has approval from an IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

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Investigating the Causal Role of Prefrontal Control in Decision-making in Patients With Anhedonia

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