e-PAT Neuromod Evaluation of Personalized rTMS for Resistant Depression

NCT02410421 | Withdrawn Phase 2

• 1 other identifier: 5055
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

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

Outcome Measures

Primary Outcomes (2)

• 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).

  difference between before (D-7 to -1) and after (D+15 to +21) each therapeutic protocol (D = day of the beginning of the protocol)

• 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).

  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 Outcomes (2)

• 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)

• 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)

Other Outcomes (5)

• 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 ("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)

• 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)

Study Arms (3)

Individualized rTMS protocol

EXPERIMENTAL

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.

Procedure: Functional magnetic resonance imaging used to individualize rTMS protocol using robotic coil positioning

High frequency rTMS as usual

ACTIVE COMPARATOR

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.

Procedure: Functional magnetic resonance imaging used to individualize rTMS protocol using robotic coil positioning

Trans-cranial direct current stimulation (tDCS)

ACTIVE COMPARATOR

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.

Procedure: Functional magnetic resonance imaging used to individualize rTMS protocol using robotic coil positioning

Interventions

Functional magnetic resonance imaging used to individualize rTMS protocol using robotic coil positioning PROCEDURE

High frequency rTMS as usual; Individualized rTMS protocol; Trans-cranial direct current stimulation (tDCS)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Strasbourg, France: lead

MeSH Terms

Conditions

Depressive Disorder

Condition Hierarchy (Ancestors)

Mood Disorders; Mental Disorders

Study Officials

• Jack FOUCHER, MD

  Service de Psychiatrie 1, Hôpitaux Universitaires de Strasbourg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 1, 2015
• First Posted: April 7, 2015
• Primary Completion: May 1, 2020
• Study Completion: May 1, 2020
• Last Updated: January 5, 2016

Record last verified: 2016-01