An interventional study of MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil. and Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil. in Treatment Resistant Depression, sponsored by Danish Research Centre for Magnetic Resonance. Recruiting at 3 sites in Denmark. Open to participants aged 18 Years to 95 Years. Per ClinicalTrials.gov, last updated 2026-08-26.
Sponsored by Danish Research Centre for Magnetic Resonance · Not applicable, Interventional, and Treatment
The CoMPACT trial is a randomized double-blinded sham-controlled study aimed at testing a novel accelerated and personalized transcranial Magnetic Stimulation (TMS) treatment for patients with Treatment Resistant Depression (TRD).
CoMPACT consists of 25 sessions of intermittent theta-burst transcranial stimulation (iTBS) consisting of high inter-pulse frequency administered five times daily over five consecutive days.
The trial will include 78 patients with TRD who will be randomly assigned to one of three groups:
The hypothesis is that real prefrontal or parietal CoMPACT targeting will significantly alleviate depression symptoms compared to sham targeting, without compromising safety, feasibility, or tolerability.
The trial incorporates a personalized approach, using electrical field (E-field) modeling based on individual structural brain scans to tailor and standardize iTBS, ensuring accurate targeting of cortical volume and consistent induced electrical field strength. To delineate the treatment mechanism of action at the brain network level, multi brain mapping models will be implemented. Electroencephalography (EEG) records of spontaneous and TMS-evoked electrical brain activity will be obtained before, during, and after iTBS sessions to understand how the high frequency burst protocol functionally engages the stimulated cortex. Structural and functional brain MRI before and after the treatment will be used to study changes in depression-related brain networks. This will offer key insights into how CoMPACT affects depression-related brain networks and may identify neuroimaging markers for predicting treatment response, and thus informing future TBS treatments for TRD.
Repetitive TMS (rTMS) of left DLPFC was approved by the US Food and Drug Administration (FDA) in 2008 as a therapy TRD, and this was extended to the equally effective iTBS protocol in 2018.
Dysfunctional connectivity between the left DLPFC and subgenual anterior cingulate cortex (sgACC) has been implicated in the pathogenesis of depression. It has been hypothesized that rTMS-induced neuroplasticity in left DLPFC modifies functional connectivity between left DLPFC and sgACC, normalizing the underlying brain circuit dysfunction.
A recent development has been a move towards "accelerated" rTMS protocols with more than one session per day. Recently, two studies reported promising results for the Stanford Accelerated Intelligent Neuromodulation Treatment (SAINT) protocol for TRD.
The aim of the COMPACT trial is to introduce and test a novel accelerated iTBS therapy for TRD that is designed to significantly expand existing work on accelerated iTBS.
The novel CoMPACT protocol utilizes high frequency bursts to produce a strong "acceleration" effect, securing therapeutic efficacy and clinical feasibility.
The COMPACT protocol consists of five iTBS sessions per day (rather than 10 sessions per day as given in the "SAINT" protocol) over five consecutive days to increase feasibility. In addition to accelerated iTBS of left DLPFC, the invetigators will test clinical efficacy of a novel parietal target, the left IPL. The investigators hypothesize that accelerated iTBS of the area in left IPL that shows a strong negative functional connectivity with the sgACC will be also highly effective in treating TRD compared to the accelerated sham protocol.
Anatomically guided personalized targeting and dosing will be based on E-field modeling informed by the individual cortical anatomy revealed by the patient's structural brain MRI.
Patients with TRD are recruited from psychiatric departments in Copenhagen. Information material with contact details for the project will be available in waiting rooms at the outpatient clinics so that potential participants can contact the project themselves. Furthermore, we will recruit by advertising via Trialtree.dk After inclusion, participants will undergo a baseline assessment (T0) that includes evaluating depression severity and several widely used psychiatric rating scales measuring anhedonia, cognitive deficits, and treatment-related adverse effects. A list of the tests included can be found in the "Outcome" section.
Within two weeks after T0, patients will undergo 5 days of active iTBS targeting either the left DLPFC or the left IPL, or a sham intervention on the left DLPFC or IPL, for a total of 25 sessions. During the first and last day of intervention week, EEG will be used recorded before, during and after first and last iTBS sessions. This helps to investigate acute changes in the cortical activity patterns induced by a single iTBS and the cumulative functional effects on cortical activity caused by the CoMPACT protocol.
Moreover, EEG response to a single and multi TMS pulse, so-called transcranial evoked potentials (TEPs), will be measured before and after iTBS session. This will allow us to explore how high-frequency burst iTBS modulates cortical excitation and inhibition in targeted regions and its potential correlation with clinical response. Online EEG monitoring during iTBS will be performed can also be used to document safety and capture brain activity during the periods separating consecutive iTBS trains.
The antidepressive effects of the intervention (Hamilton Depression Rating Scale as primary outcome) will be assessed, within 3 days after the last session. The rest of the clinical tests will be performed within 5 days after end of treatment (T1). The long-term effect on symptom of depression and other clinical effect will be tested after 4 weeks (T2) and at potential 6 months follow-up.
Assessments at T0 and T1 will also include structural (T1 and T2 weighted sequences), diffusion sensitive MRI, resting-state, and task-based functional MRI (fMRI). Task-related fMRI will reveal how the active CoMPACT intervention modifies brain activity and connectivity within key brain networks compared to sham COMPACT. Cognitive performance will be also probed using a selected set of cognitive tests at T0, T1 and T2.Referral to standard TMS therapy for non-responders:
If patients have not entered remission (i.e. a score less than 7 on HDS-17) immediately after the end of COMPACT treatment or at visit T1, they will be offered standard TMS treatment. A treatment that is approved for general clinical use in psychiatric wards and elsewhere.
Data will be collected at the participating sites in the Capital Region of Denmark (RegionH). After end of trial and final data analysis, anonymized trial-related data and methods will be made available to other researchers through public databases after publication of the main clinical outcome paper in accordance with Danish law.
448 studies on the registry are indexed under Depressive Disorder, Treatment-Resistant; 147 are open to participants now.
This study's planned enrollment of 78 is above the median of 59 across 372 interventional studies indexed under Depressive Disorder, Treatment-Resistant.
Browse Depressive Disorder, Treatment-Resistant studies →Danish Research Centre for Magnetic Resonance is the lead sponsor of 14 studies on the registry; 9 are open to participants now.
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Exclusion criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Contraception
Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.
Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil.
Device: Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil.
Device: Sham stimulation of the MagVenture MagPro XP Orange Edition Prototype flipping the active side of the MagVenture Cool-B65 coil
Intermittent theta burst stimulation (iTBS) targeting the left dorsolateral prefrontal cortex (DLPFC) will be administered over five consecutive days. On each intervention day, patients will undergo five high frequency iTBS sessions (each lasting approximately 10 minutes, excluding preparation) with about 50 minutes of rest between sessions. Each iTBS session delivers 1,800 pulses, resulting in a total of 25 sessions and 45,000 pulses over the course of a standard work week.
Intermittent theta burst stimulation (iTBS) targeting the left inferior parietal lobule (IPL) will be administered over five consecutive days using the stimulation pattern described in the active DLPFC arm.
Device: Sham stimulation of the left DLPFC or IPL will be administered using the same stimulation duration and repetition as the active iTBS. To match the subjective experience of iTBS, the sham CoMPACT uses a dedicated (Active/Placebo) stimulation coil that has both active and sham functions, generating the same sound level regardless of the type of stimulation.
Change in the Hamilton Rating Scale for Depression-6 (HDS-6) Score
The HDS-6 total score reflects the severity of depression, ranging from 0 to 24, with higher scores indicating more severe symptoms. 0-6 = normal, 7-8= mild depression, 9-11 = moderate depression, 12-22 = severe to very severe depression. A 3-point change is considered to be clinically significant, which is a very conservative criterion.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Before the first iTBS session on the first day of intervention week. 3) A day after end of intervention (+2 days). 4) Follow-up (T2): 4 weeks after end of intervention.
Change in the Hamilton Rating Scale for Depression-17 (HDS-17) Score
The HDS-17 score ranges from 0 to 52, with higher scores reflecting greater depression severity. 0-7: Normal 8-13: Mild depression 14-18: Moderate depression 19-22: Severe depression ≥23: Very severe depression
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Before the first iTBS session on the first day of intervention week. 3) A day after end of intervention (+2 days) . 4) Follow-up (T2): 4 weeks after end of intervention.
Change in the WHO-5 Well-being Index (WHO-5) score
The World Health Organization Five Well-being Index (WHO-5) score measures overall well-being on a scale of 0 to 100, with higher scores indicating better well-being. Score Interpretation: 0-28: Poor well-being, possible clinical depression 29-50: Low mood or well-being 51-100: Good well-being
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 3) Follow-up (T2): 4 weeks after end of intervention.
Change Snaith-Hamilton Pleasure Scale (SHAPS) score
SHAPS measure anhedonia. The score ranges from 0 to 14, with higher scores reflecting greater levels of anhedonia
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 3) Follow-up (T2): 4 weeks after end of intervention.
Change in Overall Anxiety Severity and Impairment Scale (OASIS) score
OASIS The score is between 0 and 20. Higher scores indicates greater levels of anxiety and impairment.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 3) Follow-up (T2): 4 weeks after end of intervention.
Visual analogue mood scale (VAMS)
Scale rating mood 1-10. Higher score indicate better mood.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) On every day of intervention. 3) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 4) Follow-up (T2): 4 weeks after end of intervention.
Change in functionality Assessment Short Test (FAST) score
FAST FAST assesses functional impairment. The total score range is 0 to 72. Higher scores indicate greater functional impairment.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 3) Follow-up (T2): 4 weeks after end of intervention.
Change in Pittsburgh Sleep Quality Index (PSQI) score
PSQI assesses sleep quality. The total score ranges from 0 to 21, with higher scores indicating poorer sleep quality.
Time frame: Baseline T0: (1 (+1) week before intervention., Postintervention (T1): 3 (+/-2 ) days after end of intervention. Follow-up (T2): 4 weeks after end of intervention.
TMS Sensation Questionnaire (TMSens_Q)
TMSens\_Q assesses and quantifies the sensation and discomfort related to transcranial magnetic stimulation.
Time frame: Intervention week: before and after the first and last sessions on both days 1 and 5
Screening for Cognitive Impairment in Psychiatry (SCIP)
The SCIP score ranges from 0 to 75, with lower scores indicating greater cognitive deficits.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 3) Follow-up (T2): 4 weeks after end of intervention.
Cognitive Complaints in Bipolar Disorder Rating Assessment (COBRA) score
COBRA uses a 4-point scale (no difficulty- severe difficulty). The score ia 0 to 36, with higher scores indicating greater cognitive difficulties.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 3) Follow-up (T2): 4 weeks after end of intervention.
Aarhus Side effect Assessment Questionnaire (ASAQ)
ASAQ uses a 5-point scale (not at all to very much). The score is from 0 to 27. higher scores indicate greater presence of side effects.
Time frame: Baseline T0: (1 (+1) week before intervention. Postintervention (T1): 3 (+/-2 ) days after end of intervention. Follow-up (T2) 4 weeks after end of intervention.
Young Mania Rating scale (YMRS)
The Young Mania Rating Scale (YMRS) is used to assess the potential risk of transcranial magnetic stimulation (TMS) inducing mania. It ranges from 0 to 60, with higher scores indicating more severe symptoms. 0-12: No significant mania 13-19: Mild mania 20-25: Moderate mania ≥26: Severe mania
Time frame: Intervention week: before the first session on Day 1 and at the end of each intervention day.
The Stroop Color and Word Test (SCWT)
SCWT uses a 4 point scale (no difficulty to severe difficulty). Fewer errors and faster completion indicate better cognitive control and executive functioning.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 3) Follow-up (T2): 4 weeks after end of intervention.
Trail Making Test A & B (TMT)
TMT-A tests the times to connect all number in correct order. TMT-B tests the total time to alternate between numbers and letters. Fewer errors and faster completion indicate better cognitive control and executive functioning.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) On the end of day 1 of intervention week. 3) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 4) Follow-up (T2): 4 weeks after end of intervention.
Nine-hole pegboard test
Nine-hole pegboard test. Fewer errors and faster completion indicate better motor skills.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) On the end of day 1 of intervention week. 3) Postintervention (T1): 3 (+/-2 ) days after end of intervention. 4) Follow-up (T2): 4 weeks after end of intervention.
Treatment Expectation Questionnaire (TEX-Q)
Question about the patient's expectations for the treatment effect.
Time frame: Baseline T0: (1 (+1) week before intervention.
Changes in magnetic resonance imaging (MRI) from baseline to postintervention
Structural MRI (sMRI) gives high-resolution images of the brain anatomy and allows for accurate calculation of different volumes of the brain regions. Diffusion MRI (dMRI) measures the regional diffusion properties of water and provides micro-structural information on the direction of fiber tracts and structural connectivity in relation to our stimulation targets. Functional MRI (fMRI) can map the functional connectivity of the brain during resting periods and during performing reward related tasks.
Time frame: 1) Baseline T0: (1 (+1) week before intervention. 2) Postintervention (T1): 3 (+/-2 ) days after end of intervention.
Changes in Resting-State EEG Power Bands
EEG will be used to assess changes in cortical activity power induced by a single iTBS session, as well as the cumulative effects across an intervention day. The analysis will cover the entire frequency spectrum, with a particular focus on the theta and alpha bands. Additionally, alterations in both periodic and aperiodic components of the power spectrum will be studied.
Time frame: Intervention week: Before and after first and last sessions on both days 1 and 5
Immediate changes in EEG power spectrum
EEG will be used to assess acute changes in cortical power spectrum between consecutive burst trains with a particular focus on the theta and alpha band. Additionally, alterations in both periodic and aperiodic components of the power spectrum will be studied.
Time frame: Intervention week: During the first and last sessions on both days 1 and 5
Changes in EEG-based Connectivity
Exploratory analysis of potential alterations in connectivity within the related network during and after a single iTBS session, compared to baseline. In addition to the investigation of a single session, the cumulative effect of multiple sessions will also be explored.
Time frame: Intervention week. Before, during and after the first and last sessions both days 1 and 5
Changes in TEPs ( transcranial evoked potentials)
TEP measurements (EEG response to single and multiple TMS pulses) will be conducted using active and sham TMS protocols. Changes in TEP components (peaks such as N45, P60, and N100) induced by a single intervention session or across multiple sessions will be studied.
Time frame: Intervention week. Before and after first and last sessions on both days 1 and 5
Heart rate variability
Electrocardiography (ECG) will measure changes in heart rate variability (HRV), specifically RR interval variability, during an iTBS session. This will serve as a heart-brain coupling index, which reflects target engagement by assessing autonomic nervous system activity in relation to neural activity.
Time frame: Intervention week. During first and last sessions on both days 1 and 5
Patient guess regarding treatment
Questionnaire assessing the patient's guess of whether they have received active or sham stimulation.
Time frame: Postintervention (T1): 3 (+/-2 ) days after end of intervention.
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Danish Research Centre for Magnetic Resonance