None listed
Conditions
Brief summary
Major depressive disorder (MDD) is a severe and common illness. It has been well established that approximately 30% of patients with MDD have an inadequate response to standard medication and psychological therapies. These patients remain disabled for long time as treatment options are limited. Current brain stimulation treatment options for MDD are costly and can be inconvenient as they may require daily trips to clinics for long treatment sessions that happen over the course of 6 weeks or more. Additionally, we are technically constrained in what we can achieve and current technologies and approach to treat MDD have generally used a ‘one size fits all’ method. Transcranial alternating current stimulation (tACS) is a novel, non-invasive brain stimulation method that delivers a weak electrical current to the brain and is able to modulate brain oscillatory activity. tACS has potential to change the lives of patients with MDD by specifically targeting brain circuits and oscillations relevant to MDD. Our approach aims to change the ‘one size fits all’ method by conducting a proof-of-concept study demonstrating the feasibility, clinical and electrophysiological impact of closed-loop theta tACS. The study will specifically aim to confirm whether theta oscillations and mood in patients with MDD can be successfully modulated by tACS. We hypothesize that a series of personalized theta tACS sessions applied to the dorsolateral prefrontal cortex (DLPFC) in patients with depression can modulate the following to a greater degree in participants who are receiving active treatment compared to sham stimulation: 1. Modulate theta activity at rest and during cognitive tasks (measured using EEG) on and emotional Stroop task and a working memory task 2. Modulate behavioral performance on both the emotional Stroop and working memory tasks. 3. Modulate depression symptoms (clinician rated and self-reported).
Interventions
Transcranial Alternating Current (tACS) is a form of non-invasive brain stimulation that delivers a weak electrical current that alternates at a specified frequency back and forth between electrodes. Administration of tACS will be provided using a custom-built tACS-EEG device called the Rio Transceiver, manufactured by eemagine Medical Imaging Solutions GmbH. The device consists of a battery-driven unit that allows for the combined recording of electroencephalography (EEG) signals and administration of tACS. The device delivers a voltage controlled current across stimulation electrodes made of conductive rubber encases in commercially supplied saline soaked sponges held in fitted cap. Stimulating electrodes will be positioned on the scalp at the 10-20 EEG system location of F5, F6 and Fz. To date, there have been an increasing number of studies exploring the potential uses of tACS and EEG, especially for improving aspects of cognition and mood in those with depression. We aim to optimize tACS treatment by individualizing the stimulation frequency delivered. This is determined by using EEG to measure the in-phase peak theta activation for each individual (individual theta frequency; ITF). The ITF will be measured with EEG at the beginning of each session and will be recalibrated and adjusted by the device accordingly during the rest periods between blocks (creating a closed-loop tACS-EEG design). For all active tACS conditions, a peak-to-peak intensity of 1.5mA will be administered for each participant for a maximum of 20 minutes with a 10s ramp-up and 10s ramp-down every time the stimulation starts and stops. Participant will be asked to complete daily treatment sessions (i.e 5 days/week) over 4 weeks. On site: During a given treatment session, participant is required to be awake, alert and aware. The study researcher will provide clear instructions on where the participant is to be seated and demonstrate how to prepare the tACS-EEG cap and fit it to the participant's head. The stimulation and EEG electrodes in the cap are connected to a battery driven, portable device (i.e. the Rio Transceiver). Administration of tACS and recording with EEG will be automatically triggered while participants complete a series of working memory tasks. Participants will be aware that tACS is given while they complete each block of the working memory tasks. Each block is designed to run for 5 minutes over 4 blocks. tACS ceases at the end of each block, during which participants can rest from the task. After a minimum of 30 sec rest (participant can take a longer break if needed), participants will be given instructions on the screen to press a key to continue with the next block. The total duration of the breaks between blocks may vary depending on participants needs, although it will be recommended that the breaks do not exceed 5 minutes. EEG will be used to record brain activity for 1 minute, during which participants are instructed to remain still and relaxed with their eyes open. Following the completion of the working memory tasks, the study researcher will remove the cap and demonstrate how to clean and care for the equipment. Sessions on-site are not limited; participants will be able to attend all sessions on-site until competency to carry out at home sessions is clearly demonstrated. At home: All procedures outlined above will be presented to participants in a way that will teach them how to self-administer treatment at home. As the treatment itself (tACS and EEG) is pre-programmed into the device and triggered by participants as they complete a highly guided series of working memory tasks. Participants will primarily need to know how to prepare the cap and clean the cap for each session. Prior to being allowed to proceed with home-based treatment, participants will need to complete a competency assessment for self-administration. The first 2 at home sessions will be supervised by study researchers via video call. In addition, the device is designed to collect data about the location, date, start and end times of stimulation, side effects experienced, and comments. This data is for researchers to monitor and view and will be used to ensure compliance to the protocol. If participants miss a scheduled treatment session, this will be evident to researchers as there will be absences in data stored. We will also remain in close contact with participants throughout to ensure continued appropriate use and address issues as they arise promptly.
Sponsors
Australian National University
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
- Diagnosis of major depressive disorder as a single or recurrent episode, in accordance with the Diagnostic and Statistical Manual of Mental Disorders edition 5 (DSM-V) -18 to 80 years of age - Montgomery-Asberg Depression Rating Scale (MADRS) score of > 19 ( moderate-severe depression) - No change or initiation of new antidepressant (or other psychoactive) therapy in the four weeks prior to treatment - Demonstrated capacity to give informed consent
Exclusion criteria
- Inability to provide informed consent - Medically unstable - concomitant active neurological disorder - Patients who are pregnant or breastfeeding - Active suicidal intent - Any psychotic disorder or current active psychotic symptoms - Patients with intracranial implants - Another Axis I or Axis II disorder judged to impact on the likelihood of response to treatment. - fails tACS safety screening (e.g. says yes to having a metal implant in head)
Outcome results
None listed