COpenhagen Magnetic Personalized Accelerated Brain Circuit Therapy for Treatment Resistant Depression

NCT06895863 | Recruiting

• 3 other identifiers: CoMPACT10.46540/3166-00150BPrecision-BCT - 9068-00025A
• Study Type: interventional
• Target: 78
• Locations: 1 country
• Sites: 3

Brief 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). 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.

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)

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  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

  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)

  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.

Other Outcomes (7)

• Changes in magnetic resonance imaging (MRI) from baseline to postintervention

  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

  Intervention week: Before and after first and last sessions on both days 1 and 5

• Immediate changes in EEG power spectrum

  Intervention week: During the first and last sessions on both days 1 and 5

Study Arms (3)

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

Interventions

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.

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. 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.

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 coil DEVICE

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.

Sham Comparator: Sham stimulation to either left IPL (50%) or left DLPFC (50%)

Eligibility Criteria

• Age: 18 Years - 95 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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
• 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.

Sponsors & Collaborators

• Danish Research Centre for Magnetic Resonance: lead
• Glostrup University Hospital, Copenhagen: collaborator
• Mental Health Center North Zealand: collaborator

Study Sites (3)

Centre of Neuropsychiatric Depression Research

Glostrup Municipality, 2600, Denmark

RECRUITING

Mental Health Center North Zealand

Hilleroed, 3400, Denmark

NOT YET RECRUITING

Danish Research Centre for Magnetic Resonance

Hvidovre, 2650, Denmark

NOT YET RECRUITING

Related Publications (7)

• 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.

  PMID: 34711062 BACKGROUND

• Cole 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.

  PMID: 32252538 BACKGROUND

• Voigt 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.

  PMID: 34050123 BACKGROUND

• Kan 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.

  PMID: 36898403 BACKGROUND

• Ressler 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.

  PMID: 17726478 BACKGROUND

• Fox 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.

  PMID: 22658708 BACKGROUND

• Cash 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.

  PMID: 32800379 BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depressive Disorder, Major

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Hartwig Siebner, Professor

  Danish Researach Centre for Magnetic Resonance

  PRINCIPAL INVESTIGATOR

• Poul Videbech, Professor

  Center for Neuropsychiatric Depression Research, Mental health Center Glostrup

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Poul Videbech, Professor

CONTACT

+4538640634; poul.videbech@regionh.dk

Iman Ibrahim, MD

CONTACT

+4591175914; IIBR0007@regionh.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Double-blinded randomized sham controlled

Study Record Dates

• First Submitted: January 16, 2025
• First Posted: March 26, 2025
• Study Start: January 15, 2025
• Primary Completion (Estimated): January 31, 2028
• Study Completion (Estimated): September 1, 2028
• Last Updated: January 22, 2026

Record last verified: 2026-01

Locations

DK (3)