Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia

Treatment Resistant Clinical Trial

— RETONIC  

Official title:

Personalized Non-invasive Neuromodulation by rTMS for Chronic and Treatment Resistant Catatonia - A Proof of Concept Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03116425
• Other study ID #: 6441
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 24, 2017
• Est. completion date: June 2022

Study information

• Verified date: April 2022
• Source: University Hospital, Strasbourg, France
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 17
• Est. completion date: June 2022
• Est. primary completion date: June 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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.

Related Conditions & MeSH terms

• Catatonia
• Schizophreniform Catatonia
• Treatment Resistant

Intervention

Device:
• Individualized rTMS on VERUM 1's region or network
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
• Individualized rTMS on VERUM 2's region or network
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
• Individualized rTMS on PLACEBO region
Region will be modulated up or down according to the stimulation protocol used in VERUM 1 and 2 conditions. Stimulation will be replicated up to 5 times per session. Patients will have 4 sessions per day on 5 successive days per arm.

Procedure:
• Individualized rTMS on VERUM 1's region or network
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
• Individualized rTMS on VERUM 2's region or network
To increase cortical rCBF, iTB (intermittent theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 2 sec with an inter-train interval of 8 sec. To decrease cortical rCBF, cTB (continuous theta burst) will be used: triplet at 50 Hz repeated at 5 Hz in trains of 40 sec. Intensity 120% of passive threshold (or 150% of active threshold). Stimulation protocol will be used up to 5 times per session to allow a reasonable regional or network coverage. Patients will have 4 sessions per day on 5 successive days per arm.
• Individualized rTMS on PLACEBO region
Region will be modulated up or down according to the stimulation protocol used in VERUM 1 and 2 conditions. Stimulation will be replicated up to 5 times per session. Patients will have 4 sessions per day on 5 successive days per arm.

Locations

Country	Name	City	State
France	CEMNIS	Strasbourg

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change of rCBF anomalies	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 average of 2 · 3 (=6) measures of rCBF using QUIPS2 arterial spin labeling sequence on a Siemens 3T Verio. We will compare the rCBF change of the target region before and after the therapeutic protocol between the different procedures (ANOVA).	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).
Primary	Clinical global impression (change in severity and improvement)	Clinical Global Impression - Severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis.; Clinical Global Impression - Improvement scale (CGI-I) is a 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention	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	Change in personalized daily visual analogical scales assessing the core symptoms.	This scale has been validated	Points results will be averaged over the 4 days before and after each therapeutic arm.
Secondary	Change in Bush and Francis Catatonia Rating Scale.	This scale has been validated.	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)
Secondary	Change in psychosis: PANSS.	This scale has been validated.	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)
Secondary	Change in depression: Calgary Depression Scale.	This scale has been validated.	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)
Secondary	Change in apathy: actimetry, apathy inventory and apathy evaluation scale.	This scale has been validated.	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)
Secondary	Change in obsessive compulsive symptoms: Brief Obsessive Compulsive Scale	This scale has been validated.	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)
Secondary	Change in obsessive compulsive symptoms: Cambridge-Exeter Repetitive Thought Scale.	This scale has been validated.	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)
Secondary	Change in quality of life for the patient (SF36)	All these scales have been validated.	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)
Secondary	Change in the helping person ("Zarit scale")	This scale has been validated.	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)
Secondary	Change in functioning: Global Assessment of Functioning (GAF scale)	This scale has been validated.	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)
Secondary	Change in functioning: WHODAS 2.0.	This scale has been validated.	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)