Major Depressive Disorder
Conditions
Keywords
transcranial alternating current stimulation, cross-frequency coupling, behavioral activation
Brief summary
Investigating whether delta-beta cross-frequency transcranial alternating current stimulation can augment the effects of a single session of behavioral activation in participants with major depressive disorder.
Detailed description
The purpose of this study is to examine whether concurrent transcranial alternating current stimulation (tACS) augments the effects of a single session behavioral activation (BA) treatment of depression. Following a series of clinical assessments, participants will perform a reward-based decision-making task while electroencephalography (EEG) is collected. Then, all participants will take part in a single-session 90-minute BA intervention; half of the participants will receive delta-beta tACS during the final 30 minutes of the session and half will receive an active sham stimulation. Participants will return two weeks later for another task-based EEG. Four weeks after the intervention session, they will receive self-report questionnaires via email to complete online.
Interventions
DEVICEDelta-beta cross-frequency transcranial alternating current stimulation via the NeuroConn DC-STIMULATOR MC
Delta-beta stimulation will be delivered via the NeuroConn DC-STIMULATOR MC, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
BEHAVIORALSingle-session behavioral activation
Participants will take part in a single-session behavioral activation (BA) intervention. This intervention was adapted from standard BA protocols for the treatment of depression to be completed in a single, 90-minute session. This intervention will have 4 main components based on prior protocols: * Treatment overview and rationale * Tracking of daily activities * Exploration of values * Planning/scheduling activities
DEVICEActive sham cross-frequency transcranial alternating current stimulation via the NeuroConn DC-STIMULATOR MC
Active sham stimulation will be delivered via the NeuroConn DC-STIMULATOR MC, an investigational electrical non-invasive brain stimulation device that is being used for foundational neuroscience and translational research.
Sponsors
Foundation of Hope, North Carolina
University of North Carolina, Chapel Hill
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Masking description
This study is designed to be double-blind. This means that the participant and the researchers are unaware of each participant's assignment until the completion of all data collection. This is accomplished using the randomization codes described above. Furthermore, this study utilizes an active sham stimulation. The active sham condition includes brief stimulation, mimicking the skin sensations associated with tACS. In our previously concluded trial, participants in the delta-beta tACS and active sham groups responded similarly to the blinding questionnaire, indicating that our active sham stimulation successfully blinded the participants.
Intervention model description
Participants will take part in a single-session behavioral activation (BA) intervention. To examine the effects of neurostimulation on treatment response, participants will be randomized to receive either delta-beta cross-frequency transcranial alternating current stimulation (tACS) or an active sham.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 18 years old or order * Able to provide informed consent * Willing to comply with all study procedures and be available for the duration of the study * Speak and understand English * DSM-5 diagnosis of major depressive disorder (MDD) as assessed by the MINI
Exclusion criteria
* Participants must not have active suicide intent as determined by the Columbia Suicide Severity Rating Scale (C-SSRS). Active suicide intent will be captured in responses to items 4 and/or 5 on the C-SSRS. * Participants must not meet criteria for current severe substance use disorder, anorexia nervosa, or active psychosis as captured by the MINI. * Participants may not currently be in psychotherapy and have not received any other psychotherapy and/or stimulation (ECT, TMS) within the last 4 weeks. * Any participants taking psychotropic medication must be on a stable dose for at least 4 weeks with no planned dose changes within the next 4 weeks. * (for female participants) Participants must not be pregnant or breastfeeding. * Participants may not have any medical or neurological illness for which symptom presentation or treatment could interfere with study participation * Participants may not have undergone prior brain surgery * Participants may not have any brain devices/implants, including cochlear implants and aneurysm clips * Participants may not have had brain injury or concussion within the last three months * Participants may not have a history of brain injury requiring current treatment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinician-rated Depressive Symptoms | Baseline, 2 weeks post treatment | Treatment response will be reported for clinician-rated depression symptom scores using the Hamilton Depression Rating Scale (HDRS). Items are scaled either from 0-2 to 0-4, and each item is summed for a total score ranging from 0 to 53 with higher scores indicating greater depression symptoms. Benchmarks suggested at: 0-7 normal; 8-13 mild depression; 14-18 moderate depression; 19-22 severe depression; \>=23 very severe depression. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase-amplitude Coupling (PAC) Between Delta-beta Oscillations During Task Performance of the Streamlined Expenditure of Effort for Reward Task (S-EEfRT) | Baseline, 2 weeks post treatment | Participants choose to complete a hard task or easy task. Coupling during the hard/easy decision is calculated between delta oscillations phase (2-3Hz) in prefrontal electrodes (FCz and surrounding electrodes) and the beta oscillations amplitude (15-25Hz) in left motor electrodes (C3 and surrounding electrodes). Instantaneous phase & amplitude of oscillations is calculated by averaging the signal in the two regions, band-filtering the signal to the specified range, and performing the Hilbert transform. PAC is normalized by creating a null distribution randomly shifting the beta time series by at least 10% of the number of time points. PAC is calculated between the delta-phase time series and each randomly shifted beta-amplitude time series. PAC is z-transformed relative to the null distribution. Values range from -3 to 3 and a score \>=0.4 means the coupling is present. A higher value represents greater coupling strength which has been linked with greater cognitive processing. |
| Proportion of Hard Trials Chosen During the S-EEfRT | Baseline, 2 weeks post treatment | In the Streamlined Expenditure of Effort for Reward Task (S-EEfRT), participants choose to complete a hard task requiring many button presses or an easy task with fewer button presses for variable monetary incentives. Number of button presses is individualized for each participant. Goal-directed behavior will be calculated as the proportion of hard tasks chosen across trials. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Change in Clinician-rated Anhedonia Symptoms Using SHAPS-C | Baseline up to follow-up 2 weeks post treatment | The Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) is a clinician administered tool to assess symptoms of anhedonia. The SHAPS-C items use a Likert scale of 1-4, with higher scores reflecting greater pathology. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Delta-beta tACS Participants will receive a 90- minute single session intervention of behavioral activation (BA) psychotherapy. Stimulation will be delivered during the final 30 minutes via the NeuroConn DC-STIMULATOR MC at 1 milliampere (mA) zero-to-peak amplitude at the target electrodes and 2 mA zero to-peak amplitude at the return electrode. The tACS will be delivered using the cross-frequency stimulation waveform delta-beta (3-20Hz). | 15 |
| Active-sham tACS Participants will receive a 90-minute single session intervention of behavioral activation (BA) psychotherapy. The active sham condition includes brief stimulation beginning in the final 30 minutes, mimicking the skin sensations associated with tACS, assisting with blinding the participant's assignment. | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Active-sham tACS | Total | Delta-beta tACS |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 1 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 15 Participants | 29 Participants | 14 Participants |
| Age, Continuous | 35.6 years STANDARD_DEVIATION 13.56 | 36.2 years STANDARD_DEVIATION 15.56 | 36.8 years STANDARD_DEVIATION 17.78 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 5 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 12 Participants | 25 Participants | 13 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 14 Participants | 24 Participants | 10 Participants |
| Region of Enrollment United States | 15 Participants | 30 Participants | 15 Participants |
| Sex: Female, Male Female | 10 Participants | 21 Participants | 11 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 4 / 15 | 6 / 15 |
| serious Total, serious adverse events | 0 / 15 | 0 / 15 |
Outcome results
Primary
Clinician-rated Depressive Symptoms
Treatment response will be reported for clinician-rated depression symptom scores using the Hamilton Depression Rating Scale (HDRS). Items are scaled either from 0-2 to 0-4, and each item is summed for a total score ranging from 0 to 53 with higher scores indicating greater depression symptoms. Benchmarks suggested at: 0-7 normal; 8-13 mild depression; 14-18 moderate depression; 19-22 severe depression; \>=23 very severe depression.
Time frame: Baseline, 2 weeks post treatment
Population: Three participants randomized to the sham condition did not complete the follow-up visit. Missing data for these participants was handled using the intent-to-treat last value carried forward method.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delta-beta tACS | Clinician-rated Depressive Symptoms | Baseline | 19.33 score on a scale | Standard Deviation 4.59 |
| Delta-beta tACS | Clinician-rated Depressive Symptoms | 2 weeks post treatment | 11.33 score on a scale | Standard Deviation 5.15 |
| Active-sham tACS | Clinician-rated Depressive Symptoms | Baseline | 19.93 score on a scale | Standard Deviation 4.71 |
| Active-sham tACS | Clinician-rated Depressive Symptoms | 2 weeks post treatment | 13.93 score on a scale | Standard Deviation 6.23 |
p-value: 0.34ANOVA
Secondary
Phase-amplitude Coupling (PAC) Between Delta-beta Oscillations During Task Performance of the Streamlined Expenditure of Effort for Reward Task (S-EEfRT)
Participants choose to complete a hard task or easy task. Coupling during the hard/easy decision is calculated between delta oscillations phase (2-3Hz) in prefrontal electrodes (FCz and surrounding electrodes) and the beta oscillations amplitude (15-25Hz) in left motor electrodes (C3 and surrounding electrodes). Instantaneous phase & amplitude of oscillations is calculated by averaging the signal in the two regions, band-filtering the signal to the specified range, and performing the Hilbert transform. PAC is normalized by creating a null distribution randomly shifting the beta time series by at least 10% of the number of time points. PAC is calculated between the delta-phase time series and each randomly shifted beta-amplitude time series. PAC is z-transformed relative to the null distribution. Values range from -3 to 3 and a score \>=0.4 means the coupling is present. A higher value represents greater coupling strength which has been linked with greater cognitive processing.
Time frame: Baseline, 2 weeks post treatment
Population: Data were not properly collected for some participants due to technical difficulties.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delta-beta tACS | Phase-amplitude Coupling (PAC) Between Delta-beta Oscillations During Task Performance of the Streamlined Expenditure of Effort for Reward Task (S-EEfRT) | Baseline | 0.286 Z-score | Standard Deviation 0.606 |
| Delta-beta tACS | Phase-amplitude Coupling (PAC) Between Delta-beta Oscillations During Task Performance of the Streamlined Expenditure of Effort for Reward Task (S-EEfRT) | 2 weeks post treatment | 0.286 Z-score | Standard Deviation 0.786 |
| Active-sham tACS | Phase-amplitude Coupling (PAC) Between Delta-beta Oscillations During Task Performance of the Streamlined Expenditure of Effort for Reward Task (S-EEfRT) | Baseline | 0.290 Z-score | Standard Deviation 0.516 |
| Active-sham tACS | Phase-amplitude Coupling (PAC) Between Delta-beta Oscillations During Task Performance of the Streamlined Expenditure of Effort for Reward Task (S-EEfRT) | 2 weeks post treatment | 0.044 Z-score | Standard Deviation 0.655 |
p-value: 0.54ANOVA
Secondary
Proportion of Hard Trials Chosen During the S-EEfRT
In the Streamlined Expenditure of Effort for Reward Task (S-EEfRT), participants choose to complete a hard task requiring many button presses or an easy task with fewer button presses for variable monetary incentives. Number of button presses is individualized for each participant. Goal-directed behavior will be calculated as the proportion of hard tasks chosen across trials.
Time frame: Baseline, 2 weeks post treatment
Population: Data were not properly collected for some participants due to technical difficulties.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Delta-beta tACS | Proportion of Hard Trials Chosen During the S-EEfRT | Baseline | 0.562 proportion of trials | Standard Deviation 0.158 |
| Delta-beta tACS | Proportion of Hard Trials Chosen During the S-EEfRT | 2 weeks post treatment | 0.504 proportion of trials | Standard Deviation 0.188 |
| Active-sham tACS | Proportion of Hard Trials Chosen During the S-EEfRT | Baseline | 0.521 proportion of trials | Standard Deviation 0.205 |
| Active-sham tACS | Proportion of Hard Trials Chosen During the S-EEfRT | 2 weeks post treatment | 0.454 proportion of trials | Standard Deviation 0.103 |
p-value: 0.865ANOVA
Other Pre-specified
Change in Clinician-rated Anhedonia Symptoms Using SHAPS-C
The Snaith-Hamilton Pleasure Scale-Clinician (SHAPS-C) is a clinician administered tool to assess symptoms of anhedonia. The SHAPS-C items use a Likert scale of 1-4, with higher scores reflecting greater pathology.
Time frame: Baseline up to follow-up 2 weeks post treatment