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.
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.
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
Danish Research Centre for Magnetic Resonance
Lead sponsor
Glostrup University Hospital, Copenhagen
Collaborator
Mental Health Center North Zealand
Collaborator