COpenhagen Magnetic Personalized Accelerated Brain Circuit Therapy for Treatment Resistant Depression

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

Interventions

DEVICE

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

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

Sham stimulation of the MagVenture MagPro XP Orange Edition Prototype flipping the active side of the MagVenture Cool-B65 coil

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.

Sponsors & Collaborators

• Center for Neuropsychiatric Depression Research (CNDR), Mental Health Centre Glostrup

  collaborator UNKNOWN

• Mental Health Center North Zealand

  collaborator UNKNOWN

• Danish Research Centre for Magnetic Resonance

  lead OTHER

Principal Investigators

• Hartwig Siebner, Professor · Danish Researach Centre for Magnetic Resonance

• Poul Videbech, Professor · Center for Neuropsychiatric Depression Research, Mental health Center Glostrup

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

95 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2025-01-15

Primary Completion

2028-01-31

Completion

2028-09-01

Countries

• Denmark

Study Locations