Major Depressive DisorderDBANCT06132581
Causal Role of Delta-beta Coupling for Goal-directed Behavior in Anhedonic Depression
A study testing Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 and Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 in people with Major Depressive Disorder and Anhedonia, run by Florida State University at 1 site in United States.
Trial summary
Anhedonia, the inability to seek-out and experience pleasure, is a common symptom in depression that predicts treatment-resistance and is sometimes exacerbated by first-line antidepressants. In our previous research, we found that anhedonia decreases goal-directed behavior and its related neural activity. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Anhedonia
- What is being tested?
- Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 and Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 72 participants
- Where
- 1 siteUnited States
- Study dates
- 24 Jan 2024to 31 Jul 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Between the ages of 18 and 65
- 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
- Mild suicide risk as determined by the Hamilton Depression Rating Scale (HAM-D; less than 3 for the suicidality item) and non-existent or mild risk according to the Depression Symptom Index Suicidality Subscale (DSI-SS).
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- Patient Health Questionnaire (PHQ-8) greater than or equal to 8 prior to the first session
- Snaith Hamilton Pleasure Scale (SHAPS) greater than 33 at the first session
- A diagnosis of major depressive disorder on the Mini International Neuropsychiatric Interview for the DSM-V (MINI)
Who cannot join
- ADHD (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. For example, unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment
- Prior brain surgery
- Any brain devices/implants including cochlear implants and aneurysm clips, cardiac pacemaker, or any other implanted electronic device
- History of current traumatic brain injury
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- Pregnancy (for females)
- Current severe substance use disorder
- Claustrophobia
- Based on the use of MRI, additional exclusion/inclusion criteria are considered. Note that many contraindications for stimulation are common with MRI and thus are not repeated. Participants must not have metal in the body that is ferrous, will be required to remove all jewelry, must not have tattoos on the face or neck, must refrain from wearing metal in clothing (underwire) or active gear (possibility of metallic microparticle technology), must not be a metal worker or have an eye injury involving metal.
- 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
- DSM-V 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Florida State University
Tallahassee, Florida, 32306
Justin M Riddle, PhD, 850-645-2389, jriddle@fsu.edu
Justin M Riddle, PhD
About this study
Anhedonia, the inability to seek-out and experience pleasure, is a common symptom in depression that predicts treatment-resistance and is sometimes exacerbated by first-line antidepressants. In our previous research, we found that anhedonia decreases goal-directed behavior and its related neural activity. In this study, we will investigate target engagement from five-consecutive days of stimulation for participants that are within a unipolar major depressive episode and also have high symptoms of anhedonia.
Read the detailed description
The experiment comprises eight sessions total. People that request to be in the experiment will first complete demographic and self-report clinical assessments. People that meet our eligibility criteria will be invited to participate in the study. In the first session, clinical assessment are administered to determine eligibility for the full study. In the second session, participants complete a functional magnetic resonance imaging (MRI) session in which they complete three different reward-based decision-making tasks. After the MRI session, participants are randomized into one of three parallel arms to receive five consecutive days of cross-frequency transcranial alternating current stimulation (CF-tACS) in either delta-beta, control-frequency (theta-gamma), or placebo (sham) CF-tACS. In the third through seventh session, participants receive 40 minutes of CF-tACS while completing goal-setting and action planning worksheets. Before the first session of CF-tACS (the third session overall) and the last session of CF-tACS (the seventh session overall), participants complete brief self-report clinical assessments. On the third and seventh session (the first and fifth day of CF-tACS), the participant will complete the reward-based decision-making tasks prior to stimulation while EEG is recorded. In these two sessions, resting-state EEG is acquired before and after stimulation. The first and fifth session of tACS (third and seventh session overall) will take approximately three hours to complete. The second through fourth session of tACS (fourth through sixth session overall) will take approximately one hour to complete. In the follow-up session, visit 8, (approximately two weeks after the end of the five-days of stimulation), participants return for an in-person session that includes self-report clinical assessments and EEG during the reward-based decision-making tasks.
- Conditions
- Major Depressive Disorder, Anhedonia
- Being tested
- Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4, Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4, Sham tACS via the Neurocare Direct Current Stimulator Multi-Channel 4
- Keywords
- Transcranial alternating current stimulation, Goal-directed behavior, Cross-frequency coupling
- Medical subject headings
- Depressive Disorder, Major, Anhedonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4Device
Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform for stimulation was designed to mimic delta-beta coupling in the brain.
Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4Device
Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform for stimulation was designed to mimic theta-gamma coupling in the brain and is used as an active comparator.
Sham tACS via the Neurocare Direct Current Stimulator Multi-Channel 4Device
Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform is randomly selected to be the theta-gamma or delta-beta waveform, but the stimulation is delivered for only a brief period of time of approximately 30 seconds, which is not sufficient to produce a meaningful dose to the brain. This placebo, or sham, stimulation is designed to mimic the sensation of receiving stimulation.
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Device: Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 |
| 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). Receives: Device: Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 |
| Active-sham tACS | Sham comparator | For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 15 seconds only at the beginning and end of the stimulation period. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset and offest of stimulation, assisting with blinding the participant's assignment. Receives: Device: Sham tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in coupling strength between prefrontal and posterior cortex
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 the S-EEfRT during the decision period. 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.
Measured: 1 week
Secondary outcomes (1)
Change in Symptoms of anhedonia
Anhedonia is measured using the Snaith Hamilton Pleasure Rating Scale (SHAPS) which ranges from 14 to 56 where a larger value reflects greater symptoms of anhedonia.
Measured: 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Nov 2023
- Study start24 Jan 2024
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Florida State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants are randomized into one of three arms of the study: delta-beta tACS, control tACS in theta-gamma, or active sham tACS.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Florida State University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Justin Riddle, Florida State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06132581
- Sponsor's protocol ID
- STUDY00004503
- Other IDs
- 4R00MH126161-03
- Acronym
- DBA
- Status last verified
- Aug 2026
- First submitted
- 7 Nov 2023
- Last updated
- 31 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Yes: 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 FSU.
Study at a glance
From the registry record, last updated by the sponsor on 31 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Causal Role of Delta-beta Coupling for Goal-directed Behavior in Anhedonic Depression
- ClinicalTrials.gov ID
- NCT06132581
- Acronym / sponsor ID
- DBA / STUDY00004503
- Conditions
- Major Depressive Disorder, Anhedonia
- Keywords
- Transcranial alternating current stimulation, Goal-directed behavior, Cross-frequency coupling
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- Florida State UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 24 Jan 2024 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Jul 2027 (estimated)
- First posted
- 15 Nov 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Anhedonia, the inability to seek-out and experience pleasure, is a common symptom in depression that predicts treatment-resistance and is sometimes exacerbated by first-line antidepressants. In our previous research, we found that anhedonia decreases goal-directed behavior and its related neural activity. In this study, we will investigate target engagement from five-consecutive days of stimulation for participants that are within a unipolar major depressive episode and also have high symptoms of anhedonia.
Detailed description
The experiment comprises eight sessions total. People that request to be in the experiment will first complete demographic and self-report clinical assessments. People that meet our eligibility criteria will be invited to participate in the study. In the first session, clinical assessment are administered to determine eligibility for the full study. In the second session, participants complete a functional magnetic resonance imaging (MRI) session in which they complete three different reward-based decision-making tasks. After the MRI session, participants are randomized into one of three parallel arms to receive five consecutive days of cross-frequency transcranial alternating current stimulation (CF-tACS) in either delta-beta, control-frequency (theta-gamma), or placebo (sham) CF-tACS. In the third through seventh session, participants receive 40 minutes of CF-tACS while completing goal-setting and action planning worksheets. Before the first session of CF-tACS (the third session overall) and the last session of CF-tACS (the seventh session overall), participants complete brief self-report clinical assessments. On the third and seventh session (the first and fifth day of CF-tACS), the participant will complete the reward-based decision-making tasks prior to stimulation while EEG is recorded. In these two sessions, resting-state EEG is acquired before and after stimulation. The first and fifth session of tACS (third and seventh session overall) will take approximately three hours to complete. The second through fourth session of tACS (fourth through sixth session overall) will take approximately one hour to complete. In the follow-up session, visit 8, (approximately two weeks after the end of the five-days of stimulation), participants return for an in-person session that includes self-report clinical assessments and EEG during the reward-based decision-making tasks.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
- Model description
- Participants are randomized into one of three arms of the study: delta-beta tACS, control tACS in theta-gamma, or active sham tACS.
| Arm | Type | Receives |
|---|---|---|
| Delta-beta tACS | Experimental | Device: Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4The 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). |
| Theta-gamma tACS | Active comparator | Device: Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4This arm serves as an active control where tACS will be delivered using the cross-frequency stimulation waveform theta-gamma (5-50Hz). |
| Active-sham tACS | Sham comparator | Device: Sham tACS via the Neurocare Direct Current Stimulator Multi-Channel 4For active sham stimulation, either delta-beta or theta-gamma stimulation is delivered for 15 seconds only at the beginning and end of the stimulation period. This is intended to mimic the skin sensations (e.g., itching, burning, tingling) that are experienced at the onset and offest of stimulation, assisting with blinding the participant's assignment. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Between the ages of 18 and 65
- 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
Key exclusion criteria (12 listed)
- ADHD (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. For example, unstable cardiac disease, HIV/AIDS, malignancy, liver or renal impairment
- Prior brain surgery
- Any brain devices/implants including cochlear implants and aneurysm clips, cardiac pacemaker, or any other implanted electronic device
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform for stimulation was designed to mimic delta-beta coupling in the brain. | Device | Delta-beta tACS |
| Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform for stimulation was designed to mimic theta-gamma coupling in the brain and is used as an active comparator. | Device | Theta-gamma tACS |
| Sham tACS via the Neurocare Direct Current Stimulator Multi-Channel 4Stimulation will be delivered via the Neurocare Direct Current Stimulator Multi-Channel 4, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research. The electrical waveform is randomly selected to be the theta-gamma or delta-beta waveform, but the stimulation is delivered for only a brief period of time of approximately 30 seconds, which is not sufficient to produce a meaningful dose to the brain. This placebo, or sham, stimulation is designed to mimic the sensation of receiving stimulation. | Device | Active-sham tACS |
Primary outcome
Change in coupling strength between prefrontal and posterior cortex
Time frame: 1 week
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 the S-EEfRT during the decision period. 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.
1 secondary outcome
Change in Symptoms of anhedonia
Time frame: 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 31 Aug 2026.
- Individual participant dataSharing planned: Yes. 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 FSU.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Delta-beta tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 and Theta-gamma tACS via the Neurocare Direct Current Stimulator Multi-Channel 4 in people with Major Depressive Disorder and Anhedonia, run by Florida State University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 31 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Justin M Riddle, PhD (850-645-2389, jriddle@fsu.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in coupling strength between prefrontal and posterior cortex (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Aug 2026.