An interventional study of Transcranial Magnetic Stimulation and Transcranial Alternating Current Stimulation in Depression - Major Depressive Disorder, sponsored by Mersey Care NHS Trust. Not yet recruiting at 2 sites in United Kingdom. Open to participants aged 18 Years to 59 Years. Per ClinicalTrials.gov, last updated 2026-10-19.
Sponsored by Mersey Care NHS Trust · Not applicable, Interventional, and Basic science
Major depressive disorder (MDD) is a common and disabling condition. Transcranial magnetic stimulation (TMS) is an established non-invasive neuromodulation treatment for depression, but clinical response varies considerably between individuals. One possible reason for this variability is that the effects of TMS may depend on the pattern of ongoing brain activity at the time stimulation is delivered.
This mechanistic, randomised, single-blind study will investigate whether synchronising TMS with transcranial alternating current stimulation (tACS), a form of weak electrical brain stimulation, can enhance the neurophysiological and cognitive effects of TMS in people experiencing a current moderate major depressive episode. The combined intervention is referred to as synchronised TMS (tsTMS).
Up to 60 participants will be recruited and randomised in a 1:1:1 ratio to one of three groups: (1) TMS synchronised to the peak of a theta-frequency tACS waveform, (2) TMS synchronised to the trough of a theta-frequency tACS waveform, or (3) TMS combined with sham tACS. Participants will receive five daily neuromodulation sessions over one week.
The primary objective is to estimate variability in change in emotional processing, measured using the Cambridge Cognition Emotional Bias Task, in order to inform the design and sample size calculation of a future clinical trial. The study will also assess participant acceptability and tolerability of the intervention. Secondary objectives include exploring changes in brain oscillatory activity measured using electroencephalography (EEG), cognitive performance, mood and anxiety symptoms, functional outcomes, and digital biomarkers collected from an optional wearable device.
This study is designed to investigate mechanisms and feasibility rather than provide a full therapeutic course of TMS. Findings will be used to inform the development of a future definitive clinical trial evaluating whether synchronised neuromodulation can improve outcomes in depression.
2,805 studies on the registry are indexed under Depressive Disorder, Major; 565 are open to participants now.
This study's planned enrollment of 60 is below the median of 80 across 2,338 interventional studies indexed under Depressive Disorder, Major.
Browse Depressive Disorder, Major studies →Mersey Care NHS Trust is the lead sponsor of 2 studies on the registry; 1 is open to participants now.
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Device: Transcranial Magnetic Stimulation · Device: Transcranial Alternating Current Stimulation
Device: Transcranial Magnetic Stimulation · Device: Transcranial Alternating Current Stimulation
Device: Transcranial Magnetic Stimulation
Transcranial Magnetic Stimulation (TMS) is a non-invasive neuromodulation intervention delivered using a magnetic coil positioned over the scalp to generate brief magnetic pulses that stimulate targeted cortical brain regions.
Also known as: TMS
Transcranial Alternating Current Stimulation (tACS) is a non-invasive neuromodulation intervention that delivers a weak alternating electrical current through electrodes placed on the scalp to modulate neural oscillatory activity in targeted brain regions.
Also known as: tACS
Change in emotional bias (Cambridge Neuropsychological Test Automated Battery (CANTAB) Emotional Bias task)
Difference in shift of emotional bias between participants who receive five sessions of tsTMS (tACS + TMS) and participants who receive TMS alone (the two forms of tsTMS under study will be individually compared to TMS).
Time frame: First measured at the baseline session (28 days within the first stimulation session), then measured at the fifth stimulation session, and finally repeated at the follow-up session (within 7 days +/- 3 days after the final, fifth stimulation session)
Frequency of adverse effects and tolerability
Total adverse effects score derived from the participant-completed adverse effects questionnaire administered after each stimulation session. The total score combines the frequency and severity of reported adverse effects.
Time frame: After each of the five stimulation sessions.
Participant experience and acceptability
Participant perceptions of the acceptability and experience of receiving tsTMS or TMS with sham tACS and of participating in the study, assessed through a semi-structured qualitative interview.
Time frame: Follow-up visit within 7 days (±3 days) after the fifth stimulation session
Change in task-related theta-frequency brain oscillatory activity
Change in task-related theta-frequency brain oscillatory activity following neuromodulation, measured using electroencephalography (EEG). The outcome will compare changes in the fronto-midline theta activity during a working memory task between participants receiving tsTMS and those receiving TMS with sham tACS.
Time frame: Stimulation Day 1. Pre-stimulation to post-stimulation (multiple timepoints at 5 min and 30 min post-stimulation) within the same session.
Change in Frontal Theta Power
Change in resting-state frontal theta power measured using EEG during eyes-open and eyes-closed conditions before and after neuromodulation. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Stimulation Day 1. Pre-stimulation to post-stimulation (multiple timepoints at 5min and 30min post-stimulation) within the same session.
Change in Central Beta Power
Change in resting-state central beta power measured using electroencephalogram (EEG) during eyes-open and eyes-closed conditions before and after neuromodulation. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Stimulation Day 1. Pre-stimulation to post-stimulation (multiple timepoints at 5min and 30min post-stimulation) within the same session.
Change in Occipital Alpha Power
Change in resting-state occipital alpha power measured using EEG during eyes-open and eyes-closed conditions before and after neuromodulation. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Stimulation Day 1. Pre-stimulation to post-stimulation (multiple timepoints at 5min and 30min post-stimulation) within the same session.
Change in Subjective Cognitive Difficulties (Perceived Deficits Questionnaire for Depression, 5-item version (PDQ-5-D))
Change in subjective cognitive difficulties from baseline to follow-up, assessed using the Perceived Deficits Questionnaire (PDQ-5-D). Changes following tsTMS will be compared with TMS with sham tACS. Total scores range from 0 to 20, with higher scores indicating greater perceived cognitive difficulties and lower scores indicating better subjective cognitive functioning.
Time frame: Baseline and follow-up visit (within 7 days ±3 days after the fifth stimulation session).
Change in Choice Reaction Time
Change in reaction time performance from baseline to follow-up, assessed using the THINC-it Choice Reaction Time task. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Baseline and follow-up visit (within 7 days ± 3 days after the fifth stimulation session).
Change in Digit Symbol Substitution Test (DSST) Performance
Change in cognitive performance from baseline to follow-up, assessed using the Digit Symbol Substitution Test (DSST). Changes following tsTMS will be compared with TMS with sham tACS. The score is the total number of correct symbol-digit substitutions completed during the test period. Higher scores indicate better cognitive performance and faster processing speed, while lower scores indicate poorer performance.
Time frame: Baseline and follow-up visit (within 7 days ± 3 days after the fifth stimulation session).
Change in Physical Activity Levels
Change in physical activity levels measured using the optional EmbracePlus wearable device. Activity metrics include actigraphy-derived activity measures and step count. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Continuously from baseline assessment until the follow-up visit (approximately 1 to 5 weeks).
Change in Gait Characteristics
Change in gait characteristics measured using the optional EmbracePlus wearable device from baseline to follow-up. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Continuously from baseline assessment until the follow-up visit (approximately 1 to 5 weeks).
Change in Sleep Metrics
Change in sleep-related measures recorded using the optional EmbracePlus wearable device from baseline to follow-up. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Continuously from baseline assessment until the follow-up visit (approximately 1 to 5 weeks).
Change in Pulse Rate
Change in pulse rate measured using the optional EmbracePlus wearable device from baseline to follow-up. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Continuously from baseline assessment until the follow-up visit (approximately 1 to 5 weeks).
Change in Skin Temperature
Change in skin temperature measured using the optional EmbracePlus wearable device from baseline to follow-up. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Continuously from baseline assessment until the follow-up visit (approximately 1 to 5 weeks).
Change in Electrodermal Activity
Change in electrodermal activity measured using the optional EmbracePlus wearable device from baseline to follow-up. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Continuously from baseline assessment until the follow-up visit (approximately 1 to 5 weeks).
Change in Respiratory Rate
Change in respiratory rate measured using the optional EmbracePlus wearable device from baseline to follow-up. Changes following tsTMS will be compared with TMS with sham tACS.
Time frame: Continuously from baseline assessment until the follow-up visit (approximately 1 to 5 weeks).
Plan to share: No — Individual participant data (IPD) collected during this study will not be made available to other researchers due to participant confidentiality, consent limitations, and data governance requirements.
Start is estimated for Sep 2026; primary completion for Aug 2027, 11 months later.
Of 612 non-industry interventional studies with no phase under Depressive Disorder, Major, half reached primary completion within 31 months of starting (the median), counting those still running; a quarter within 17 and three quarters within 53. This study's planned 11 months is below that.
Counting every sponsor, half of 652 studies reached it within 30 months; a quarter within 16 and three quarters within 53.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
This study is not yet recruiting, as verified in Aug 2026. You cannot join it, but the record below documents what was studied.
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Mersey Care NHS Trust