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

Intervention / Treatment

• 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

Primary Outcome Measures

• Change in the Hamilton Rating Scale for Depression-6 (HDS-6) 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.)
  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.

Countries

Denmark

Locations and Investigators

• Centre of Neuropsychiatric Depression Research, Glostrup Municipality, Denmark (Recruiting)
  • Line Fønss
  • Iman B M E Ibrahim, MD, PhD-student
• Mental Health Center North Zealand, Hilleroed, Denmark (Not yet recruiting)
  • Maj Vinberg, Professor
• Danish Research Centre for Magnetic Resonance, Hvidovre, Denmark (Not yet recruiting)
  • Hartwig Siebner, Professor
  • Armita Faghani, Post.doc.

Study Officials

• 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