Depressive Disorder, Treatment-Resistant
Conditions
Keywords
Individualized Medicine, Transcranial Magnetic Stimulation, Repetitive, Transcranial Direct Current Stimulation Monocentric, Compariative Cross-Over 3 Arms Study Randomized, Single-Blind Method, Functional Neuroimaging
Brief summary
The investigators hypothesize that personalizing the rTMS targets using functional MRI will increase its efficacy. The most dysfunctional regions or the most dysfunctional network will be stimulated homogeneously. Individualized rTMS will be compared to traditional rTMS procedure and to trans-cranial direct current stimulation (tDCS) in a randomized cross-over trial. In this pilot study the 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
Procedure consisting in personalizing the rTMS targets and stimulation pattern based on functional magnetic resonance imaging
DEVICEIndividualized rTMS (transcranial magnetic stimulation)
DEVICEClassical rTMS (transcranial magnetic stimulation)
DEVICEClassical tDCS (transcranial direct current stimulation)
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 |
|---|---|---|
| Change of rCBF anomalies | Difference between before (assessed once between D-7 to -1) and after (assessed once between 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. rCBF will be measured using the average of 2 ∙ 3 (=6) measures of rCBF using QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. rCBF change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA). 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. Contrast map of each patient will be compared to the one of a control population submitted to the same analysis. Change in the number of above threshold voxels (F-test, p \< 0.05 uncorrected, extension \> 1 cm3) will be compared before & after therapeutic procedure (ANOVA). rCBF's change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA). |
| Change of the functional connectivity anomalies | Difference between before (assessed once between D-7 to -1) and after (assessed once between 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. rCBF will be measured using the average of 2 ∙ 3 (=6) measures of rCBF using QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. rCBF change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA). 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. Contrast map of each patient will be compared to the one of a control population submitted to the same analysis. Change in the number of above threshold voxels (F-test, p \< 0.05 uncorrected, extension \> 1 cm3) will be compared before & after therapeutic procedure (ANOVA). rCBF's change of the target region will be compared before & after therapeutic protocol between the different procedures (ANOVA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in symptoms evaluated by the clinician (QIDS16-C) | Difference between before (assessed once between D-7 to -1) and after (assessed once between 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). |
| Change in symptoms evaluated by the patient (QIDS30-SR) | Difference between before (assessed once between D-7 to -1) and after (assessed once between 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 |
|---|---|
| Daily visual analogical scales assessing the core symptoms | Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol). |
| 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). |
| Quality of life (Echele 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). |
| 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). |
Countries
France
Outcome results
None listed