Pre-mapping Networks for Brain Stimulation 2

Study Overview
=================
Brief Summary
-----------------
The investigators compare the primary and secondary outcome measures using accelerated intermittent theta burst stimulation (aiTBS, 20 sessions active and 20 sessions sham in a counterbalanced crossover design) to treat depressive symptoms with 2 parallel arms of intervention: personalized (stimulation position based on participants' brain networks) vs conventional (stimulation in F3 position of the 10-20 EEG cap) aiTBS.

Official Title
-----------------
Untersuchung Von Hirnnetzwerken Durch Nicht-invasive Transkranielle Magnetstimulation - Phase 2 (PreNeSt2)

Conditions
-----------------
Depressive Episode, Major Depressive Disorder

Intervention / Treatment
-----------------
* Device: Neuronavigated aiTBS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Men and women between the ages of 18 and 60 years Diagnosis of major depressive disorder according to DSM 5 (F32.x according to ICD-10) or bipolar disorder (bipolar I or bipolar II) according to DSM 5 (F31.x according to ICD-10) and an acute depressive condition at the time of the initial examination in outpatient or inpatient treatment (e.g. Department of Psychiatry and Psychotherapy, UMG) Availability of informed consent to participate in the study, including the examinations and interventions Exclusion Criteria: Neurological diseases, current or previous Other Axis I diagnoses that mimic the affective disorder, current or previous Physical illnesses that could be related to the affective symptoms (so-called organic causes) Illicit drug use in the past month Substance dependence, current or previous Physical illnesses which, depending on their type and severity, could interfere with the planned examinations, influence the parameters to be examined or endanger the test participant during the course of the examination Medical contraindications against performing an MRT examination / rTMS application (such as metal parts in the body, e.g. implants, pacemakers, infusion pumps, metal splinters, etc.) Pregnancy Previously known cerebral-morphological abnormalities (e.g. tumor, lesion, etc.) Evidence or history of epilepsy Head trauma with a history of loss of consciousness Unwillingness to be informed of incidental findings Participation in an rTMS / EKT application within the last 8 weeks Lack of the ability to provide informed consent

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: The investigators compare study outcomes using aiTBS in personalized stimulation targets vs conventional F3 stimulation targets in parallel arms, each arm controlled by its respective sham stimulation in a counterbalanced crossover design.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personalized aiTBS active - sham<br>counterbalanced crossover with sham neuronavigated stimulation | Device: Neuronavigated aiTBS<br>* Accelerated intermittent theta burst stimulation (aiTBS, 4 sessions per day with at least 20 minutes pause between sessions) in the left dorsolateral prefrontal cortex (DLPFC)<br>|
| Active Comparator: Conventional (F3) aiTBS active - sham<br>counterbalanced crossover with sham neuronavigated stimulation | Device: Neuronavigated aiTBS<br>* Accelerated intermittent theta burst stimulation (aiTBS, 4 sessions per day with at least 20 minutes pause between sessions) in the left dorsolateral prefrontal cortex (DLPFC)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montgomery-Åsberg Depression Rating Scale (MADRS scores in units of scale) | Administer Rating Scale | 6 weeks | 
| heart rate and its variability in RR slope and RMSSD values | Potential marker of treatment response | 4-6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hamilton Rating Scale for Depression (HAMD-17 scores in units of scale) | Administer Rating Scale | 6 weeks | 
| Beck Depression Inventory (BDI-2 scores in units of scale) | Self Rating Scale | 6 weeks | 
| DMN decoupling / other networks in rho and z values | Potential markers of treatment response | 4-6 weeks | 
| epi / genetic markers of neuroplasticity in ng | Potential markers of treatment response | 5-6 weeks |