Treatment Resistant DepressionCoMPACTNCT06895863
COpenhagen Magnetic Personalized Accelerated Brain Circuit Therapy for Treatment Resistant Depression
A study testing 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 people with Treatment Resistant Depression, run by Danish Research Centre for Magnetic Resonance at 3 sites in Denmark.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 95 years
- Conditions the study is for
- Treatment Resistant Depression
- What is being tested?
- 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.
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 78 participants
- Where
- 3 sitesDenmark
- Study dates
- 15 Jan 2025to 1 Sep 2028
- 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 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age range between 18 and 95 years
- In- or outpatients with a moderate to severe single episode or periodic MDD according to ICD-10, verified by a M.I.N.I. interview.
- Major Depression Inventory (self-rapport) score higher than 25.
- Lacking or insufficient effect of at least two drug trials from two distinct classes, e.g., SSRI, SNRI, TCA, or MAO-inhibitors, used in the current episode, with adequate dose and duration as judged by the investigator.
- Duration of the current episode must be longer than 2 months but shorter than 4 years, as judged by the investigator.
Who cannot join
- History of neurologic disease affecting the brain, including dementia and epilepsy
- Schizophrenia or any other psychotic disorder except for psychotic depression
- Head trauma causing more than 5 minutes loss of consciousness
- Suicidal or psychotic symptoms making the transport of participants hazardous
- Any form of compulsory admission or treatment within the past three months
- Treatment with ECT in the current depressive episode
Show all 14Show fewer
- Non-responders to TBS treatment within the current episode
- Current harmful use or dependency of substances according to ICD-10 and interfering with outcome evaluation as judged by investigator's discretion.
- High risk of non-adherence as judged by investigators discretion
- Medical and psychiatric conditions interfering with study outcome and safety as judged by investigator's discretion.
- Female participants of childbearing age must not be pregnant or breast feeding, and they must use contraception during the trial.
- One of the prime contra-indications for MRI, including severe claustrophobia (see Appendix 08.05)
- One of the prime contra-indications for TMS and persons with electrically, magnetically, or mechanically activated implants or with metal or magnetic pieces in their head (see Appendix 08.04)
- Patients who do not wish to be informed about MRI or EEG findings, which may have clinical relevance.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark3 sites, 3 recruiting
- Recruiting
Centre of Neuropsychiatric Depression Research
Glostrup Municipality, 2600
Line Fønss, + 4538640442 ext. +4520528617, line.foenss@regionh.dk
Iman B M E Ibrahim, MD, PhD-student, +4591175914 ext. +4553466199, IIBR0007@regionh.dk
- Not yet recruiting
Mental Health Center North Zealand
Hilleroed, 3400
Maj Vinberg, Professor, +4538643227, Maj.Vinberg@regionh.dk
- Not yet recruiting
Danish Research Centre for Magnetic Resonance
Hvidovre, 2650
Hartwig Siebner, Professor, +4538626541, hartwig.roman.siebner@regionh.dk
Armita Faghani, Post.doc., +4538621184, armitaf@drcmr.dk
About this study
Official title: The Copenhagen Magnetic Personalized Accelerated Brain Circuit Therapy (CoMPACT) Trial
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.
Read more
The trial will include 78 patients with TRD who will be randomly assigned to one of three groups:
- Group 1: Real CoMPACT targeting the left dorsolateral prefrontal cortex (DLPFC).
- Group 2: Real CoMPACT targeting a novel site, the left inferior parietal lobule (IPL).
- Group 3: Sham CoMPACT targeting the left DLPFC (50%, Group 3a) or left IPL (50%, Group 3b).
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.
Read the detailed description
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.
- Conditions
- Treatment Resistant Depression
- Being tested
- MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil., Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil., Sham stimulation of the MagVenture MagPro XP Orange Edition Prototype flipping the active side of the MagVenture Cool-B65 coil
- Keywords
- Brain circuit therapy, Major depressive disorder (MDD), Transcranial magnetic stimulation (TMS), Intermittent theta burst stimulation (iTBS), Copenhagen Magnetic Personalized Accelerated Brain Circuit Therapy (COMPACT), Treatment resistant depression (TRD)
- Medical subject headings
- Depressive Disorder, Treatment-Resistant, Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil.Device
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.
Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil.Device
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.
Sham stimulation of the MagVenture MagPro XP Orange Edition Prototype flipping the active side of the MagVenture Cool-B65 coilDevice
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.
| Study group | Role | What they receive |
|---|---|---|
| Real intermittent theta burst stimulatio (iTBS) of the dorsolateral prefrontal cortex (DLPFC) | Active comparator | Not described Receives: Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil. |
| Real intermittent theta burst stimulation (iTBS) of the left inferior parietal lobule (IPL) | Active comparator | Not described Receives: Device: Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil. |
| Sham Comparator: Sham stimulation to either left IPL (50%) or left DLPFC (50%) | Sham comparator | Not described Receives: Device: Sham stimulation of the MagVenture MagPro XP Orange Edition Prototype flipping the active side of the MagVenture Cool-B65 coil |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Secondary outcomes (16)
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
Measured: 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
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: Baseline T0: (1 (+1) week before intervention.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Mar 2025
- Study start15 Jan 2025
- Primary completion31 Jan 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for Treatment Resistant DepressionStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Double-blinded randomized sham controlled
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 78 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Danish Research Centre for Magnetic Resonance
- Sponsor type
- University, hospital or other
- Collaborators
- Glostrup University Hospital, Copenhagen, Mental Health Center North Zealand
- Responsible party
- Sponsor
- Investigators
- Hartwig Siebner, Professor, Principal investigator, Danish Researach Centre for Magnetic ResonancePoul Videbech, Professor, Principal investigator, Center for Neuropsychiatric Depression Research, Mental health Center Glostrup
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06895863
- Sponsor's protocol ID
- CoMPACT
- Other IDs
- 10.46540/3166-00150B, Precision-BCT - 9068-00025A
- Acronym
- CoMPACT
- Status last verified
- Aug 2026
- First submitted
- 16 Jan 2025
- Last updated
- 26 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.
PubMed 34711062Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, Nejad R, Pankow H, Choi E, Aaron H, Espil FM, Pannu J, Xiao X, Duvio D, Solvason HB, Hawkins J, Guerra A, Jo B, Raj KS, Phillips AL, Barmak F, Bishop JH, Coetzee JP, DeBattista C, Keller J, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am J Psychiatry. 2020 Aug 1;177(8):716-726. doi: 10.1176/appi.ajp.2019.19070720. Epub 2020 Apr 7.
PubMed 32252538Voigt JD, Leuchter AF, Carpenter LL. Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis. Transl Psychiatry. 2021 May 28;11(1):330. doi: 10.1038/s41398-021-01441-4.
PubMed 34050123Kan RLD, Padberg F, Giron CG, Lin TTZ, Zhang BBB, Brunoni AR, Kranz GS. Effects of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex on symptom domains in neuropsychiatric disorders: a systematic review and cross-diagnostic meta-analysis. Lancet Psychiatry. 2023 Apr;10(4):252-259. doi: 10.1016/S2215-0366(23)00026-3. Epub 2023 Mar 7.
PubMed 36898403Ressler KJ, Mayberg HS. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci. 2007 Sep;10(9):1116-24. doi: 10.1038/nn1944.
PubMed 17726478Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.
PubMed 22658708Cash RFH, Weigand A, Zalesky A, Siddiqi SH, Downar J, Fitzgerald PB, Fox MD. Using Brain Imaging to Improve Spatial Targeting of Transcranial Magnetic Stimulation for Depression. Biol Psychiatry. 2021 Nov 15;90(10):689-700. doi: 10.1016/j.biopsych.2020.05.033. Epub 2020 Jun 7.
PubMed 32800379Faghani Jadidi A, Ibrahim I, Christiansen L, Beck MM, Labanauskas V, Sigurdsson B, Antunes MG, Thomsen T, Hjerrild S, Thielscher A, Vinberg M, Siebner HR, Videbech P. Copenhagen Magnetic Personalized Accelerated Brain Circuit Therapy (CoMPACT) trial: study protocol for a randomized, double-blinded, sham-controlled, three-armed, parallel-group trial of transcranial magnetic stimulation for treatment-resistant depression. Front Psychiatry. 2026 Oct 2;17:1937455. doi: 10.3389/fpsyt.2026.1937455. eCollection 2026.
PubMed 42890690
Study at a glance
From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Copenhagen Magnetic Personalized Accelerated Brain Circuit Therapy (CoMPACT) Trial
- ClinicalTrials.gov ID
- NCT06895863
- Acronym / sponsor ID
- CoMPACT / CoMPACT
- Conditions
- Treatment Resistant Depression
- Keywords
- Brain circuit therapy, Major depressive disorder (MDD), Transcranial magnetic stimulation (TMS), Intermittent theta burst stimulation (iTBS), Copenhagen Magnetic Personalized Accelerated Brain Circuit Therapy (COMPACT), Treatment resistant depression (TRD)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 78 participants (estimated)
- Lead sponsor
- Danish Research Centre for Magnetic ResonanceUniversity, hospital or other
- Collaborators
- Glostrup University Hospital, Copenhagen, Mental Health Center North Zealand
- Study start
- 15 Jan 2025 (actual)
- Primary completion
- 31 Jan 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 26 Mar 2025 (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.
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:
- Group 1: Real CoMPACT targeting the left dorsolateral prefrontal cortex (DLPFC).
- Group 2: Real CoMPACT targeting a novel site, the left inferior parietal lobule (IPL).
- Group 3: Sham CoMPACT targeting the left DLPFC (50%, Group 3a) or left IPL (50%, Group 3b).
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
- Model description
- Double-blinded randomized sham controlled
| Arm | Type | Receives |
|---|---|---|
| Real intermittent theta burst stimulatio (iTBS) of the dorsolateral prefrontal cortex (DLPFC) | Active comparator | Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil. |
| Real intermittent theta burst stimulation (iTBS) of the left inferior parietal lobule (IPL) | Active comparator | Device: Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil. |
| Sham Comparator: Sham stimulation to either left IPL (50%) or left DLPFC (50%) | Sham comparator | Device: Sham stimulation of the MagVenture MagPro XP Orange Edition Prototype flipping the active side of the MagVenture Cool-B65 coil |
Who may qualify
- Ages
- 18 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age range between 18 and 95 years
- In- or outpatients with a moderate to severe single episode or periodic MDD according to ICD-10, verified by a M.I.N.I. interview.
- Major Depression Inventory (self-rapport) score higher than 25.
- Lacking or insufficient effect of at least two drug trials from two distinct classes, e.g., SSRI, SNRI, TCA, or MAO-inhibitors, used in the current episode, with adequate dose and duration as judged by the investigator.
- Duration of the current episode must be longer than 2 months but shorter than 4 years, as judged by the investigator.
Key exclusion criteria (14 listed)
- History of neurologic disease affecting the brain, including dementia and epilepsy
- Schizophrenia or any other psychotic disorder except for psychotic depression
- Head trauma causing more than 5 minutes loss of consciousness
- Suicidal or psychotic symptoms making the transport of participants hazardous
- Any form of compulsory admission or treatment within the past three months
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 |
|---|---|---|
| MagVenture XP Orange Stimulator and active side of 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. | Device | Real intermittent theta burst stimulatio (iTBS) of the dorsolateral prefrontal cortex (DLPFC) |
| Device: MagVenture XP Orange Stimulator and active side of MagVenture COOL-B65 coil.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 | Real intermittent theta burst stimulation (iTBS) of the left inferior parietal lobule (IPL) |
| Sham stimulation of the MagVenture MagPro XP Orange Edition Prototype flipping the active side of the MagVenture Cool-B65 coilDevice: 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. | Device | Sham Comparator: Sham stimulation to either left IPL (50%) or left DLPFC (50%) |
Primary outcome
Change in the Hamilton Rating Scale for Depression-6 (HDS-6) Score
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.
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.
16 secondary outcomes
Change in the Hamilton Rating Scale for Depression-17 (HDS-17) Score
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
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
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
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)
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
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
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)
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)
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
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)
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)
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)
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)
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
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)
Time frame: Baseline T0: (1 (+1) week before intervention.
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 26 Aug 2026.
- Background: PubMed 34711062Cole EJ, Phillips AL, Bentzley BS, Stimpson KH, Nejad R, Barmak F, Veerapal C, Khan N, Cherian K, Felber E, Brown R, Choi E, King S, Pankow H, Bishop JH, Azeez A, Coetzee J, Rapier R, Odenwald N, Carreon D, Hawkins J, Chang M, Keller J, Raj K, DeBattista C, Jo B, Espil FM, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Neuromodulation Therapy (SNT): A Double-Blind Randomized Controlled Trial. Am J Psychiatry. 2022 Feb;179(2):132-141. doi: 10.1176/appi.ajp.2021.20101429. Epub 2021 Oct 29.
- Background: PubMed 32252538Cole EJ, Stimpson KH, Bentzley BS, Gulser M, Cherian K, Tischler C, Nejad R, Pankow H, Choi E, Aaron H, Espil FM, Pannu J, Xiao X, Duvio D, Solvason HB, Hawkins J, Guerra A, Jo B, Raj KS, Phillips AL, Barmak F, Bishop JH, Coetzee JP, DeBattista C, Keller J, Schatzberg AF, Sudheimer KD, Williams NR. Stanford Accelerated Intelligent Neuromodulation Therapy for Treatment-Resistant Depression. Am J Psychiatry. 2020 Aug 1;177(8):716-726. doi: 10.1176/appi.ajp.2019.19070720. Epub 2020 Apr 7.
- Background: PubMed 34050123Voigt JD, Leuchter AF, Carpenter LL. Theta burst stimulation for the acute treatment of major depressive disorder: A systematic review and meta-analysis. Transl Psychiatry. 2021 May 28;11(1):330. doi: 10.1038/s41398-021-01441-4.
- Background: PubMed 36898403Kan RLD, Padberg F, Giron CG, Lin TTZ, Zhang BBB, Brunoni AR, Kranz GS. Effects of repetitive transcranial magnetic stimulation of the left dorsolateral prefrontal cortex on symptom domains in neuropsychiatric disorders: a systematic review and cross-diagnostic meta-analysis. Lancet Psychiatry. 2023 Apr;10(4):252-259. doi: 10.1016/S2215-0366(23)00026-3. Epub 2023 Mar 7.
- Background: PubMed 17726478Ressler KJ, Mayberg HS. Targeting abnormal neural circuits in mood and anxiety disorders: from the laboratory to the clinic. Nat Neurosci. 2007 Sep;10(9):1116-24. doi: 10.1038/nn1944.
- Background: PubMed 22658708Fox MD, Buckner RL, White MP, Greicius MD, Pascual-Leone A. Efficacy of transcranial magnetic stimulation targets for depression is related to intrinsic functional connectivity with the subgenual cingulate. Biol Psychiatry. 2012 Oct 1;72(7):595-603. doi: 10.1016/j.biopsych.2012.04.028. Epub 2012 Jun 1.
- Background: PubMed 32800379Cash RFH, Weigand A, Zalesky A, Siddiqi SH, Downar J, Fitzgerald PB, Fox MD. Using Brain Imaging to Improve Spatial Targeting of Transcranial Magnetic Stimulation for Depression. Biol Psychiatry. 2021 Nov 15;90(10):689-700. doi: 10.1016/j.biopsych.2020.05.033. Epub 2020 Jun 7.
- Derived from this study: PubMed 42890690Faghani Jadidi A, Ibrahim I, Christiansen L, Beck MM, Labanauskas V, Sigurdsson B, Antunes MG, Thomsen T, Hjerrild S, Thielscher A, Vinberg M, Siebner HR, Videbech P. Copenhagen Magnetic Personalized Accelerated Brain Circuit Therapy (CoMPACT) trial: study protocol for a randomized, double-blinded, sham-controlled, three-armed, parallel-group trial of transcranial magnetic stimulation for treatment-resistant depression. Front Psychiatry. 2026 Oct 2;17:1937455. doi: 10.3389/fpsyt.2026.1937455. eCollection 2026.
- Individual participant dataSharing planned: Undecided
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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.
Hartwig Siebner, Professor principal investigator
Danish Researach Centre for Magnetic Resonance
Poul Videbech, Professor principal investigator
Center for Neuropsychiatric Depression Research, Mental health Center Glostrup
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing 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 people with Treatment Resistant Depression, run by Danish Research Centre for Magnetic Resonance at 3 sites in Denmark.
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 5 inclusion and 14 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 26 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 3 sites in Denmark. 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 Poul Videbech, Professor (+4538640634 ext. Line Fønns, re, poul.videbech@regionh.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in the Hamilton Rating Scale for Depression-6 (HDS-6) Score (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06895863, which also lists 8 linked publications.
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 26 Aug 2026.