Clinical trial NCT03116425: Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia
Official title: Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia - A Proof of Concept Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Schizophreniform Catatonia
Treatment Resistant
Keywords: Precision Medicine
Functional Neuroimaging
Transcranial Magnetic Stimulation, Repetitive
Transcranial Direct Current Stimulation
Monocentric
Comparative balanced, randomized
double-blind cross-over 3 Arms Study
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2017-04-17
Enrollment: 17
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Investigators hypothesize that personalizing rTMS targets using functional MRI will allow to improve symptoms of patients suffering from chronic catatonia.

Detailed description: Two dysfunctional networks or regions will be chosen (verum 1 and 2) based on their abnormal rCBF. In line with the symptoms, dorso-lateral prefrontal and premotor regions are expected to be chiefly concerned. A normal region regarding its rCBF will be used as placebo. Targets will be stimulated using intermittent or continuous theta-burst according to the rCBF anomaly as an attempt to "normalize" their activity. The coil will be positioned using a robotic device under the control of a neuronavigation system in order to deliver a homogeneous stimulation. Using a balanced blinded randomized cross-over design, patients will be stimulated on 5 consecutive days (4 sessions per day) and evaluated pre-, post-stimulation and 1 month after. In this pilot study the primary outcome measures will be the clinical global impression scale whereas MRI will insure that stimulations achieved the correction of the rCBF anomalies. Secondary outcome measures will include personalized target symptom scales, and scales for catatonic, apathic and obsessive-compulsive symptoms.

Eligibility criteria: Inclusion criteria:

* Aged from 18 to 70 Y
* Affiliated to the health insurance
* Having signed an informed consent
* Suffering from catatonia according to the DSM5, unremitted since \> 2Y
* Unresponsive or incomplete remission after at least one trial of benzodiazepine and/or Electroconvulsivotherapy
* 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
* Patients unable to give informed consent.

Primary outcomes:
measure: Clinical global impression (change in severity and improvement)
timeFrame: In term of percentage reduction in symptoms, difference between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Secondary outcomes:
measure: Change in personalized daily visual analogical scales assessing the core symptoms.
timeFrame: Points results will be averaged over the 4 days before and after each therapeutic arm.
measure: Change in Bush and Francis Catatonia Rating Scale.
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in psychosis: PANSS.
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in depression: Calgary Depression Scale.
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in apathy: actimetry, apathy inventory and apathy evaluation scale.
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in obsessive compulsive symptoms: Brief Obsessive Compulsive Scale
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in obsessive compulsive symptoms: Cambridge-Exeter Repetitive Thought Scale.
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in quality of life for the patient (SF36)
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in the helping person ("Zarit scale")
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in functioning: Global Assessment of Functioning (GAF scale)
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
measure: Change in functioning: WHODAS 2.0.
timeFrame: Points involvement in scale between before (assessed on D1) and after (assessed on D5 to 7) and at 1 month after each therapeutic protocol (D = day of the beginning of the protocol)
Other outcomes:
measure: Change of rCBF anomalies
timeFrame: Points involvement in scale 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).
Locations:
city: Strasbourg
country: France
facility: CEMNIS
Study officials:
affiliation: Hôpitaux Universitaires de Strasbourg
name: Jack FOUCHER, MD
role: PRINCIPAL_INVESTIGATOR
References: