Back to resultse-PAT Neuromod Evaluation of Personalized rTMS for Resistant Depression
Primary Purpose
Depressive Disorder, Treatment-Resistant
Status
Withdrawn
Phase
Phase 2
Locations
Study Type
Interventional
Intervention
Functional magnetic resonance imaging used to individualize rTMS protocol using robotic coil positioning
Sponsored by
About this trial
This is an interventional treatment trial for Depressive Disorder focused on measuring 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
Eligibility Criteria
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
Sites / Locations
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Active Comparator
Active Comparator
Arm Label
Individualized rTMS protocol
High frequency rTMS as usual
Trans-cranial direct current stimulation (tDCS)
Arm Description
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. The therapeutic protocol will be design to correct the rCBF anomaly first by defining each point where to deliver the stimulation than the stimulation protocol for each point (180% of active motor threshold, 4-second 10 Hz train duration, with 26-second intertrain interval for a total of 3000 pulses). The whole target will be homogeneously stimulated. The active motor threshold will be assessed. The programmed protocol will be delivered while a figure of eight coil will be positioned by a robotic device (Axilum Robotics). The procedure will be repeated twice a day for 10 days over 2 weeks.
rTMS will be performed as usual using a figure-eight coil: Defining the active motor threshold. For each session positioning the coil 5 cm ahead of the abductor pollicis brevis muscle, stimulating at 180% of active motor threshold (10 Hz, 4-second train duration, and 26-second intertrain interval) for 37.5 minutes (3000 pulses per session), twice a day for 10 days over 2 weeks. Coil and stimulator will remain the same between individualized and "as usual" proceedures.
tDCS will be performed as usual: After controlling for skin healthiness, the anode and the cathode will be respectively placed over F3 and F4. A commercial devices (MagStim), will deliver a constant current of 2 mA through 25 cm2 saline-soaked rubber sponges for 20 min per session. The procedure will be repeated twice a day for 10 days over 2 weeks.
Outcomes
Primary Outcome Measures
Reduction of the target regional cerebral blood flow (rCBF) anomaly
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
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 Outcome Measures
Symptoms evaluated by the clinician (QIDS16-C)
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)
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).
Full Information
NCT ID
NCT02410421
First Posted
April 1, 2015
Last Updated
January 4, 2016
Sponsor
University Hospital, Strasbourg, France
1. Study Identification
Unique Protocol Identification Number
NCT02410421
Brief Title
e-PAT Neuromod Evaluation of Personalized rTMS for Resistant Depression
Official Title
Validation of Individualized rTMS Protocol Using Non Invasive Functional Brain Imaging and Robotic Coil Placement in Resistant Depression: Comparison With Classical rTMS and tDCS
Study Type
Interventional
2. Study Status
Record Verification Date
January 2016
Overall Recruitment Status
Withdrawn
Study Start Date
undefined (undefined)
Primary Completion Date
May 2020 (Anticipated)
Study Completion Date
May 2020 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Strasbourg, France
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Depressive Disorder, Treatment-Resistant
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
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Crossover Assignment
Masking
Care Provider
Allocation
Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Individualized rTMS protocol
Arm Type
Experimental
Arm Description
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.
The therapeutic protocol will be design to correct the rCBF anomaly first by defining each point where to deliver the stimulation than the stimulation protocol for each point (180% of active motor threshold, 4-second 10 Hz train duration, with 26-second intertrain interval for a total of 3000 pulses). The whole target will be homogeneously stimulated.
The active motor threshold will be assessed. The programmed protocol will be delivered while a figure of eight coil will be positioned by a robotic device (Axilum Robotics).
The procedure will be repeated twice a day for 10 days over 2 weeks.
Arm Title
High frequency rTMS as usual
Arm Type
Active Comparator
Arm Description
rTMS will be performed as usual using a figure-eight coil: Defining the active motor threshold. For each session positioning the coil 5 cm ahead of the abductor pollicis brevis muscle, stimulating at 180% of active motor threshold (10 Hz, 4-second train duration, and 26-second intertrain interval) for 37.5 minutes (3000 pulses per session), twice a day for 10 days over 2 weeks.
Coil and stimulator will remain the same between individualized and "as usual" proceedures.
Arm Title
Trans-cranial direct current stimulation (tDCS)
Arm Type
Active Comparator
Arm Description
tDCS will be performed as usual: After controlling for skin healthiness, the anode and the cathode will be respectively placed over F3 and F4. A commercial devices (MagStim), will deliver a constant current of 2 mA through 25 cm2 saline-soaked rubber sponges for 20 min per session. The procedure will be repeated twice a day for 10 days over 2 weeks.
Intervention Type
Procedure
Intervention Name(s)
Functional magnetic resonance imaging used to individualize rTMS protocol using robotic coil positioning
Primary Outcome Measure Information:
Title
Reduction of the target regional cerebral blood flow (rCBF) anomaly
Description
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).
Time Frame
difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Title
Reduction of the functional connectivity anomalies
Description
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).
Time Frame
difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Secondary Outcome Measure Information:
Title
Symptoms evaluated by the clinician (QIDS16-C)
Description
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).
Time Frame
difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Title
Symptoms evaluated by the patient (QIDS30-SR)
Description
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).
Time Frame
difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Other Pre-specified Outcome Measures:
Title
Response time and accuracy at the attentional network test
Description
Switch or mixed states (MAThyS)
NAA/Choline and Lactate of the target (NMR spectroscopy)
Time Frame
Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Title
Quality of life ("Echelle synoptique des 3 temps")
Description
Switch or mixed states (MAThyS)
NAA/Choline and Lactate of the target (NMR spectroscopy)
Time Frame
difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Title
Global Assessment of Functioning
Description
Switch or mixed states (MAThyS)
NAA/Choline and Lactate of the target (NMR spectroscopy)
Time Frame
Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Title
Activity measured by an actimeter
Description
Switch or mixed states (MAThyS)
NAA/Choline and Lactate of the target (NMR spectroscopy)
Time Frame
Difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)
Title
Acceptance of each therapeutic procedure
Description
Feeling comfortable with the environment (visual analog scale), this will be evaluated at each stimulation
Time Frame
We will directly compare each therapeutic protocol by averaging this value from D1 to D12.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jack FOUCHER, MD
Organizational Affiliation
Service de Psychiatrie 1, Hôpitaux Universitaires de Strasbourg
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
e-PAT Neuromod Evaluation of Personalized rTMS for Resistant Depression
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