Personalized rTMS for Resistant Depression

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Primary Purpose

Status

Terminated

Phase

Not Applicable

Locations

France

Study Type

Interventional

Intervention

Functional magnetic resonance imaging used to individualize rTMS protocol

Individualized rTMS (transcranial magnetic stimulation)

Classical rTMS (transcranial magnetic stimulation)

Classical tDCS (transcranial direct current stimulation)

About this trial

This is an interventional treatment trial for Depressive Disorder focused on measuring Individualized Medicine, Transcranial Magnetic Stimulation, Repetitive, Transcranial Direct Current Stimulation Monocentric, Compariative Cross-Over 3 Arms Study Randomized, Single-Blind Method, Functional Neuroimaging

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Service de Psychiatrie 1, Hôpital Civil, Hôpitaux Universitaires de Strasbourg

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Arm Label

Individualized rTMS (transcranial magnetic stimulation)

Classical rTMS (transcranial magnetic stimulation)

Classical tDCS (transcranial direct current stimulation)

Arm Description

The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). 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 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 on F3, 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.

tDCS will be performed as usual: After controlling for skin healthiness, the anode and the cathode will be respectively placed over F3 and right shoulder. 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

Change of rCBF anomalies

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

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 Outcome Measures

Change in 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).

Change in 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

NCT02863380

First Posted

August 2, 2016

Last Updated

March 22, 2023

Sponsor

University Hospital, Strasbourg, France

1. Study Identification

Unique Protocol Identification Number

NCT02863380

Brief Title

Personalized rTMS for Resistant Depression

Official Title

Validation of Personalized Antidepressant Treatment by Neuromodulation - Pilot Study

Study Type

Interventional

2. Study Status

Record Verification Date

March 2023

Overall Recruitment Status

Terminated

Why Stopped

The research objectives are achieved, demonstrating the feasibility and superiority of the personalized approach. It was no longer justified to continue the inclusions in this 'proof of concept' type study.

Study Start Date

May 4, 2016 (Actual)

Primary Completion Date

January 21, 2021 (Actual)

Study Completion Date

January 21, 2021 (Actual)

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

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.

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, Transcranial Magnetic Stimulation, Repetitive, Transcranial Direct Current Stimulation Monocentric, Compariative Cross-Over 3 Arms Study Randomized, Single-Blind Method, Functional Neuroimaging

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

Care Provider

Allocation

Randomized

Enrollment

27 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Individualized rTMS (transcranial magnetic stimulation)

Arm Type

Experimental

Arm Description

The target region will be defined by comparing the rCBF scan of the patient to a control population (n = 38). 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 procedure will be repeated twice a day for 10 days over 2 weeks.

Arm Title

Classical rTMS (transcranial magnetic stimulation)

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 on F3, 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.

Arm Title

Classical tDCS (transcranial direct current stimulation)

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 right shoulder. 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

Intervention Description

Procedure consisting in personalizing the rTMS targets and stimulation pattern based on functional magnetic resonance imaging

Intervention Type

Device

Intervention Name(s)

Individualized rTMS (transcranial magnetic stimulation)

Intervention Type

Device

Intervention Name(s)

Classical rTMS (transcranial magnetic stimulation)

Intervention Type

Device

Intervention Name(s)

Classical tDCS (transcranial direct current stimulation)

Primary Outcome Measure Information:

Title

Change of rCBF anomalies

Description

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).

Time Frame

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)

Title

Change of the functional connectivity anomalies

Description

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).

Time Frame

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)

Secondary Outcome Measure Information:

Title

Change in 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 (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).

Title

Change in 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 (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).

Other Pre-specified Outcome Measures:

Title

Daily visual analogical scales assessing the core symptoms

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

Response time and accuracy at the attentional network test

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 ("Echele synoptique des 3 temps")

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

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).

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

Hôpitaux Universitaires de Strasbourg

Official's Role

Principal Investigator

Facility Information:

Facility Name

Service de Psychiatrie 1, Hôpital Civil, Hôpitaux Universitaires de Strasbourg

City

Strasbourg

ZIP/Postal Code

67091

Country

France

12. IPD Sharing Statement

Plan to Share IPD

No

Depressive Disorder, Treatment-Resistant

About this trial

Eligibility Criteria

Sites / Locations

Arms of the Study

Arm 1

Arm 2

Arm 3

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

1. Study Identification

2. Study Status

3. Sponsor/Collaborators

4. Oversight

5. Study Description

6. Conditions and Keywords

7. Study Design

8. Arms, Groups, and Interventions

10. Eligibility

12. IPD Sharing Statement

Learn more about this trial