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

NCT05084924 | Completed Results FDA Device

• 2 other identifiers: 21-13211K99MH126161-01A1
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

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.

Conditions

Major Depressive Disorder; Anhedonia

Keywords

transcranial Alternating Current Stimulation; Goal-directed behavior; Cross-frequency coupling; Reward-based decision-making

Outcome Measures

Primary Outcomes (1)

• Change in the Percentage of Trials That the Participant Chooses to Perform the Hard Task

  In the Expenditure of Effort for Reward Task, participants are faced with a decision on every trial: to choose an easy task with a low effort exertion for a chance at winning a low amount of money or a hard task with a high effort exertion for a chance at winning a greater amount of money. The incentive for the high effort exertion is changed on each trial and the participant gets physically tired from repeated effort exertion. Goal-directed behavior was calculated as the percentage of trials in which the participant decides to perform the high effort exertion. The average of the 4 blocks prior to stimulation served as a baseline (1st hour). The effect of the intervention was the average of the next 8 blocks during stimulation (hours 2 through 3).

  Baseline (Hour 1), Stimulation (Hours 2 through 3)

Secondary Outcomes (1)

• Change in Coupling Strength Between Low-frequency Prefrontal Signals and High-frequency Posterior Signals

  Baseline (Hour 1), Stimulation (Hours 2 through 3)

Study Arms (3)

Delta-beta tACS

EXPERIMENTAL

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).

Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus

Theta-gamma tACS

ACTIVE COMPARATOR

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

Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus

Active-sham tACS

SHAM COMPARATOR

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.

Device: Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus

Interventions

Cross-frequency transcranial alternating current stimulation via the NeuroConn Direct Current Stimulator Plus DEVICE

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.

Active-sham tACS; Delta-beta tACS; Theta-gamma tACS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of North Carolina, Chapel Hill: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, 27599, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Anhedonia

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Justin Riddle, PhD
• Organization: University of North Carolina at Chapel Hill

justin_riddle@med.unc.edu

850-644-9869

Study Officials

• Flavio Frohlich

  University of North Carolina, Chapel Hill

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: 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.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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).

Study Record Dates

• First Submitted: October 6, 2021
• First Posted: October 20, 2021
• Study Start: November 2, 2021
• Primary Completion: July 31, 2023
• Study Completion: July 31, 2023
• Last Updated: June 25, 2024
• Results First Posted: June 25, 2024

Record last verified: 2023-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: from 9 to 36 months following publication
• 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.

Locations

US (1)