Depressive Disorder, Treatment-Resistant
Conditions
Keywords
Individualized Medicine, Functional Neuroimaging, Robotic Proceedure, Transcranial Magnetic Stimulation, Repetitive, Transcranial Direct Current Stimulation Monocentric, Compariative Cross-Over 3 Arms Study Randomized, Single-Blind Method
Brief summary
Although repetitive trans-cranial magnetic stimulation (rTMS) is an effective therapy for resistant depression, it still fail to remit up to 70% of these patients. We hypothesize that personalizing the procedure using functional MRI to better select dysfunctional regions and robotic coil placement to stimulate these regions homogeneously, will increase its efficacy. Individualized rTMS will be compared to traditional rTMS procedure and to trans-cranial direct current stimulation (tDCS). In this small proof of principle study our primary outcome measure will be the correction of the MRI anomalies. Symptoms reduction and the proportion of remitters will be secondary outcome measurements.
Interventions
PROCEDUREFunctional magnetic resonance imaging used to individualize rTMS protocol using robotic coil positioning
Sponsors
University Hospital, Strasbourg, France
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Aged from 18 to 65 Y * Affiliated to the health insurance * Having signed an informed consent * Suffering from major depression according to the DSM5 * Unresponsive or incomplete remission after at least one trial of antidepressant (\> 6 weeks at efficient dose or side effects) * Treatment stable for \> 6 weeks
Exclusion criteria
* Contraindication for MRI, rTMS or tDCS: non-removable ferromagnetic body, prosthesis, pacemaker, medication delivered by an implanted pump clip or vascular stent, heart valve or ventricular shunt, seizure disorders, skin pathology in the region of tDCS electrode placement. * Pregnancy * Severe and non-stabilized somatic pathology * Patients deprived of liberty or hospitalized without their consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of the target regional cerebral blood flow (rCBF) anomaly | difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 80). rCBF will be measured using the QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. We will compare the average rCBF of the target region before and after the therapeutic protocol between the different procedures (ANOVA). |
| Reduction of the functional connectivity anomalies | difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | Functional connectivity map of the target region will be performed by extracting its average temporal course and looking at the region(s) which activity is correlated (smoothed by a 8 mm Gaussian kernel). The contrast map of each patient will be compared to the one of a control population submitted to the same analysis. We will compare the number of above threshold voxels (F-test, p \< 0.05 uncorrected, extension \> 1 cm3) before and after the therapeutic procedure (ANOVA). We will compare the average rCBF of the target region before and after the therapeutic protocol between the different procedures (ANOVA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Symptoms evaluated by the clinician (QIDS16-C) | difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | See http://www.ids-qids.org/ for documentation relative to these scales. Computation will be performed in terms of : * Percentage of symptom reduction * Number responders (reduction of more than 50% of symptoms) * Numbers of remitters (QIDS16-C ≤ 6). |
| Symptoms evaluated by the patient (QIDS30-SR) | difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | See http://www.ids-qids.org/ for documentation relative to these scales. Computation will be performed in terms of : * Percentage of symptom reduction * Number responders (reduction of more than 50% of symptoms) * Numbers of remitters (QIDS16-C ≤ 6). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Response time and accuracy at the attentional network test | Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | * Switch or mixed states (MAThyS) * NAA/Choline and Lactate of the target (NMR spectroscopy) |
| Acceptance of each therapeutic procedure | We will directly compare each therapeutic protocol by averaging this value from D1 to D12. | Feeling comfortable with the environment (visual analog scale), this will be evaluated at each stimulation |
| Quality of life (Echelle synoptique des 3 temps) | difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | * Switch or mixed states (MAThyS) * NAA/Choline and Lactate of the target (NMR spectroscopy) |
| Global Assessment of Functioning | Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | * Switch or mixed states (MAThyS) * NAA/Choline and Lactate of the target (NMR spectroscopy) |
| Activity measured by an actimeter | Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol) | * Switch or mixed states (MAThyS) * NAA/Choline and Lactate of the target (NMR spectroscopy) |
Outcome results
None listed