Brain Stimulation And Group Therapy to Improve Gesture and Social Skills in Psychosis (BrAGG-SoS)

Study Overview
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Brief Summary
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Randomized, double-blind, placebo-controlled clinical trial testing the effects of 10 sessions of continuous theta burst stimulation and the effects of 16 sessions of social cognitive remediation therapy on gesture performance and nonverbal communication skills in schizophrenia

Detailed Description
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The study focuses on nonverbal communication skills in schizophrenia. The trial will test, whether the combination of noninvasive brain stimulation and group psychotherapy will improve gesture performance and thus nonverbal communication in schizophrenia

Official Title
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Brain Stimulation And Group Therapy to Improve Gesture and Social Skills in Psychosis (BrAGG-SoS) - a Randomized, Placebo-controlled, Double-blind Trial of Transcranial Magnetic Stimulation and Group Therapy

Conditions
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Schizophrenia

Intervention / Treatment
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* Device: continuous theta burst stimulation (cTBS)
* Device: placebo cTBS
* Behavioral: social cognitive remediation therapy (SCRT)
* Behavioral: Sham group therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Right-handed subjects Ability and willingness to participate in the study Ability to provide written informed consent Informed Consent as documented by signature schizophrenia spectrum disorders according to Diagnostic and statistical manual version 5 (DSM-5) Exclusion Criteria: Substance abuse or dependence other than nicotine Past or current medical or neurological condition associated with impaired or aberrant movement, such as brain tumors, stroke, M. Parkinson, M. Huntington, dystonia, or severe head trauma with subsequent loss of consciousness. Epilepsy or other convulsions History of any hearing problems or ringing in the ears Standard exclusion criteria for cerebral magnetic resonance imaging scanning and transcranial magnetic stimulation (TMS); e.g. metal implants, claustrophobia Patients only: any transcranial magnetic stimulation (TMS) treatment in the past 3 months Patients only: any cognitive remediation therapy in the past 2 years Women who are pregnant or breast feeding, Intention to become pregnant during the course of the study, Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential. Previous enrolment into the current study, Enrolment of the investigator, his/her family members, employees and other dependent persons

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: cTBS plus SCRT<br>10 daily sessions of continous theta burst (cTBS) on the right inferior parietal cortex for two weeks together with 16 sessions of social cognitive remediation therapy (SCRT) twice per week over an eight week period according to the manual | Device: continuous theta burst stimulation (cTBS)<br>* cTBS stimulation of 17 mins over right inferior parietal lobe (IPL) with two 44 s stimulations separated by 15 mins, 10 sessions in total (5 per week). intensity will be 100% of resting motor threshold at 30 Hz. administered in weeks 1 and 2 of the trial<br>Behavioral: social cognitive remediation therapy (SCRT)<br>* 16 sessions of group SCRT will be scheduled within 8 weeks, comprising 6-8 participants per group with 2 therapists. Duration of group sessions will be 60-90 mins. The content will follow the manual of SCRT and we will add a short intervention to practice the use of co-speech gestures at each session<br>|
| Placebo Comparator: Placebo plus SCRT<br>10 daily sessions of placebo continous theta burst (cTBS) on the right inferior parietal cortex for two weeks together with 16 sessions of social cognitive remediation therapy (SCRT) twice per week over an eight week period according to the manual | Device: placebo cTBS<br>* Placebo stimulation of 17 mins over right IPL with two 44 s stimulations separated by 15 mins, 10 sessions in total (5 per week). intensity will be 0% of resting motor threshold at 30 Hz. administered in weeks 1 and 2 of the trial<br>Behavioral: social cognitive remediation therapy (SCRT)<br>* 16 sessions of group SCRT will be scheduled within 8 weeks, comprising 6-8 participants per group with 2 therapists. Duration of group sessions will be 60-90 mins. The content will follow the manual of SCRT and we will add a short intervention to practice the use of co-speech gestures at each session<br>|
| Sham Comparator: Sham SCRT<br>16 sessions of sham social cognitive remediation therapy (SCRT) twice per week over an eight week period. Participants will engage in non-effective group activities | Behavioral: Sham group therapy<br>* Group activities in closed groups of 6 participants. Schedule of two sessions per week for 8 weeks. Two therapists are guiding different leisure activities, e.g. group walks, going to museums/movies, games.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in gesture performance using the Test of Upper Limb Apraxia (TULIA) | Test of upper limb apraxia (TULIA), recorded on video and scored according to manual. contains 48 items (gestures performed on verbal or visual instruction), total score ranges 0-240; higher scores indicate better performance. | baseline, week 2, week 8, week 32 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| change in the profile of nonverbal sensitivity (PONS) | profile of nonverbal sensitivity (PONS), short test of the interpretation of video clips, total score will be evaluated, higher scores indicate better performance | baseline, week 2, week 8, week 32 | 
| change in Brief Negative Symptoms Scale (BNSS) | rating instrument to assess severity of negative symptoms with 13 items, total score will be used ranging 0-78, higher scores indicate higher symptom severity | baseline, week 2, week 8, week 32 | 
| change in Self evaluation of negative symptoms (SNS) | questionnaire on subjective negative symptoms, includes 20 items. total scores will be used ranging 0-40 with higher scores indicating increased symptom severity | baseline, week 2, week 8, week 32 | 
| change in Social and occupational functioning (SOFAS) | rating scale on community functioning, total score is used ranging 0-100, higher scores indicated better functioning | baseline, week 2, week 8, week 32 | 
| change in the specific level of functioning assessment scale (SLOF) | rating scale on community functioning, total scores are used ranging 43-215 with higher scores indicating better functioning | baseline, week 2, week 8, week 32 | 
| change in functional capacity (UPSA brief) | brief version of the University of California in San Diego Performance-based Skills Assessment (UPSA-brief), short assessment of skills, total scores are used ranging from 0-100 with higher scores indicating better skill performance | baseline, week 2, week 8, week 32 | 
| change in neural activity during gesture planning using functional magnetic resonance imaging (fMRI) | pantomime task during functional magnetic resonance imaging. Blood oxygenation level depended (BOLD) signal change from baseline to week 8 will be compared during gesture planning within the cerebral praxis network. Standard fMRI analyses procedures will be applied | baseline, week 8 | 
| number of participants with treatment related adverse events as assessed with rating scale | after each repetitive transcranial magnetic stimulation (rTMS) session participants will be inquired about adverse events. after 5 sessions and after 10 sessions, a structured questionnaire will be applied following the guidelines for rTMS treatment. This will assess specific adverse events and their severity | week 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gesture, rTMS, cognitive remediation, social cognitive remediation therapy