STIM'ZO : Examining tDCS as an add-on Treatment for Persistent Symptoms in Schizophrenia

Not Applicable

Completed

• Conditions: Schizophrenia; Mental Disorders
• Interventions: Device: Neuroconn or Neuroelectric tDCS stimulator; Device: Sham tDCS

• Registration Number: NCT02744989
• Lead Sponsor: Hospices Civils de Lyon

Brief Summary

This project aims to provide the proof of concept for transcranial direct-current stimulation (tDCS) in the treatment of resistant/persistent Schizophrenia symptoms. The purpose is to investigate the effect of tDCS on symptoms in schizophrenic patients demonstrating a partial response to a first frequently prescribed antipsychotic medication. An early optimization of the therapeutic strategy must constitute an important factor for prognosis. Hypothesize is that tDCS should alleviate symptoms in patients depending on the clinical characteristics. In this study, stimulation is an add-on treatment to antipsychotic medication, and will be used in a broad variety of patients, i.e. in patients with varied durations of illness, various symptoms profiles, and various levels of treatment response. This in turn will allow the determination of the extent to which results can be generalized to varied patient populations, as well as the extent to which various therapeutic targets (e.g. different symptom dimensions, cognitive performance and brain connectivity) may be improved with tDCS. Despite interesting preliminary results, our team is unable to describe optimal non-invasive brain stimulation (NIBS) response markers.

This study is a randomized, double blind, controlled, French multicenter study (11 centers). The investigators plan to include 144 patients with persistent symptoms in schizophrenia. Seventy two subjects will receive active tDCS and 72 subjects will receive sham tDCS (placebo). Hypothesize is a lasting effect of active tDCS on the schizophrenic symptoms as measured by the number of responders, defined as a decrease of at least 25% of symptoms as measured by a standardized clinical scale score (PANSS) between baseline and after the 10-session tDCS regimen.

Furthermore, the participants believe that an in depth understanding of the cortical effects of tDCS could constitute an important step towards improving the technique and developing treatment response markers. An analysis of the effects on cortical activity and plasticity markers could be an interesting approach.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2016-03-18
• Study First Submitted QC: 2016-04-15
• Study First Posted: 2016-04-20
• Study Start: 2016-05-30
• Primary Completion: 2022-05
• Status Verified: 2022-10
• Study Completion: 2022-10-19
• Last Update Submitted: 2022-11-03
• Last Update Posted: 2022-11-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 141

Inclusion Criteria

1. Diagnosis of schizophrenia according to DSM 5.0 (Diagnostic and Statistical Manuel 5.0) criteria
2. Presence of symptoms despite the optimization of the antipsychotic dosage (based on prescriber's judgment) for at least 6 weeks, i.e. a dosage increase cannot be considered due to tolerability issues and/or is judged unlikely to bring sufficient clinical improvement. This will be operationalized by a minimum Negative PANSS score of 20 and at least one item scoring > 4; OR a minimum Positive PANSS score of 20 with at least one item scoring > 4 (e.g. delusion or hallucination), indicating persistent negative symptoms and/or persistent positive symptoms,
3. Patient under curatorship/guardianship or not
4. Age between 18 and 65 years old.
5. Covered by, or having the right to Social Security
6. Patient who understands the French language
7. Informed consent signed

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Exclusion Criteria

1. Other neuropsychiatric disorders (psychiatric history will be assessed using the MINI 6.0 (Mini International Neuropsychiatric Interview 6.0)) including bipolar disorders and mood depression disorders - (NB: Patients with substance related and addictive disorders will not be excluded from the study, but these data will be carefully recorded).
2. Contraindications for tDCS (neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes),
3. Increase in total composite PANSS score of at least 20% between screening and enrollment visits
4. Women who are pregnant
5. Patients whose clinical condition requires in patient procedure under constraint

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active tDCS	Neuroconn or Neuroelectric tDCS stimulator	Stimulation will be performed using an tDCS stimulator (Neuroconn or Neuroelectric tDCS stimulator) with two 7×5 cm (35 cm2) sponge electrodes soaked in a saline solution (0.9% NaCl). The anode will be placed with the middle of the electrode over a point midway between F3 and FP1 (left prefrontal cortex: dorsolateral prefrontal cortex, assumed to correspond to a region including Brodmann's Areas (BA) 8, 9, 10, and 46, depending on the patient). The cathode will be located over a point midway between T3 and P3 (left temporo-parietal junction, assumed to correspond to a region including BA 22, 39, 40, 41, and 42, depending on the patient). The stimulation level will be set at 2 mA for 20 minutes during stimulation sessions twice a day for 5 consecutive weekdays. The twice daily sessions will be separated by at least 2 hours.
Sham tDCS	Sham tDCS	-

Primary Outcome Measures

Name	Time	Method
Number of responders	Between baseline (day 0) and after 10-sessions of tDCS regimen (day 5)	The number of responders is based on the Positive and Negative Syndrome Scale (PANSS) score in the active and the sham group after 5 days of tDCS.; According to Leucht et al (2009), response is defined as a decrease of at least 25% in the Positive and Negative Syndrome Scale (PANSS, Kay et al., 1987) score after the intervention.

Secondary Outcome Measures

Name	Time	Method
Psycho-Sensory hAllucinations Scale (PSAS) score	Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session	Long-term clinical efficacy of active tDCS on schizophrenic symptoms is assessed by PSAS score measured between baseline (day 0), after 10-sessions of tDCS regimen (day 5), 1 month after tDCS (day 30), 3 months after tDCS (day 90) and 6 months after tDCS (day 180).; The PSAS score measures the delusions and severity of hallucinations
Source monitoring test score	Baseline and day 5 (after 10-sessions of tDCS regimen)	Source memory test is performed at baseline and after 10-sessions of tDCS regimen to investigate the effect of tDCS on source monitoring capacities, a cognitive function that may underlie psychotic symptoms (Brunelin et al. 2006).
Auditory Hallucination Rating Scale (AHRS) score	Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session	Long-term clinical efficacy of active tDCS on schizophrenic symptoms is assessed by AHRS score measured between baseline (day 0), after 10-sessions of tDCS regimen (day 5), 1 month after tDCS (day 30), 3 months after tDCS (day 90) and 6 months after tDCS (day 180).; The AHRS score measures the severity of auditory hallucinations.
Shortened Quality of Life questionnaire score	Baseline and 6 months after the last tDCS session	Quality of life is assessed by S-QoL18 (Shortened Quality of Life questionnaire) scale. S-QoL18 scale assesses eight dimensions : psychological well-being, self-esteem, family relationships, relationships with friends, resilience, physical well-being, autonomy and sentimental life.
Brief Medication Questionnaire (BMQ) scores	Baseline and 3 months after the last tDCS session	BMQ scores (BMQ and BMQ tDCS) assesses the effect of tDCS on patients' attitudes toward treatment of schizophrenia
Self-evaluation of Negative Symptoms (SNS) score	Baseline, 1 month and 3 months after the last tDCS session	The Self-evaluation of Negative Symptoms scale is a French self-administered questionnaire composed of 20 items organized into 5 domains of negative symptoms of schizophrenia (social withdrawal, diminished emotional range, alogia, avolition, anhedonia).
Scale to assess Unawareness of Mental Disorder (SUMD) score	Baseline and 3 months after the last tDCS session	SMUD score (Scale to assess Unawareness of Mental Disorder score) assesses the effect of tDCS on patients' attitudes toward treatment of schizophrenia
Medication Adherence rating Scale (MARS) score	Baseline and 3 months after the last tDCS session	MARS score assesses the effect of tDCS on patients' attitudes toward treatment of schizophrenia
Positive and Negative Syndrome Scale (PANSS) score	Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session	Long-term clinical efficacy of active tDCS on schizophrenic symptoms is assessed by PANSS score measured between baseline (day 0), after 10-sessions of tDCS regimen (day 5), 1 month after tDCS (day 30), 3 months after tDCS (day 90) and 6 months after tDCS (day 180).; The PANSS is a 30-item rater-administered assessment scale of the psychopathological symptoms observed in patients experiencing psychotic states, in particular schizophrenia. The items are noted from 1 to 7. It allows the calculation of the scores for three syndromic dimensions (positive, negative, and general psychopathology), both from a categorical and dimensional perspective. It is particularly recommended for determining a psychopathological profile, to look for predictive elements of an evolution, and to evaluate the respective efficacies of diverse therapeutic strategies.
Anatomical magnetic resonance imaging (MRI)	Baseline, day 5 (after 10-sessions of tDCS regimen) and 1 month after the last tDCS session	In order to evaluate treatment-related changes in functional brain connectivity, an anatomical MRI scans is performed at baseline (day 0), after 10-sessions of tDCS regimen (day 5) and 1 month after the last tDCS session (day 30).
Total serum Brain-Derived-Neurotrophic Factor (BDNF)	Baseline	Total serum BDNF level is measured to investigate the association between neural markers and clinical response to tDCS. It is hypothised that total serum BDNF is a predictive neural marker of therapeutic response.
Calgary Depression Scale for Schizophrenia (CDSS) score	Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session	Long-term clinical efficacy of active tDCS on schizophrenic symptoms is assessed by CDSS score measured between baseline (day 0), after 10-sessions of tDCS regimen (day 5), 1 month after tDCS (day 30), 3 months after tDCS (day 90) and 6 months after tDCS (day 180).; The CDSS score measures depression.
Clinical Global Impression (CGI) score	Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session	Long-term clinical efficacy of active tDCS on schizophrenic symptoms is assessed by CGI score measured between baseline (day 0), after 10-sessions of tDCS regimen (day 5), 1 month after tDCS (day 30), 3 months after tDCS (day 90) and 6 months after tDCS (day 180).; The CGI score measures the severity of symptoms and response to treatment.
Fargerström test score	Baseline, 1 month and 6 months after the last tDCS session	The Fargerström test for nicotine dependence (FTND) is a short form includes six questions designed to estimate the degree of nicotine dependence in tobacco smoking.
Functional magnetic resonance imaging (MRI)	Baseline, day 5 (after 10-sessions of tDCS regimen) and 1 month after the last tDCS session	In order to evaluate treatment-related changes in functional brain connectivity, a functional MRI scans is performed at baseline (day 0), after 10-sessions of tDCS regimen (day 5) and 1 month after the last tDCS session (day 30).
Serum Brain-Derived-Neurotrophic Factor (BDNF) isoforms	Baseline	Serum BDNF isoforms level is measured to investigate the association between neural markers and clinical response to tDCS. It is hypothised that serum BDNFisoforms is a predictive neural marker of therapeutic response.

Trial Locations

Locations (10)

CHU de St-Etienne - Service d'Urgences Psychiatriques; 🇫🇷 Saint-Etienne Cedex 2, France

Hôpital Fontan - CHRU de Lille - Pôle de Psychiatrie; 🇫🇷 Lille, France

Hôpital Edouard Herriot - Service d'Urgences Psychiatriques; 🇫🇷 Lyon cedex 03, France

Hôpital de la Colombière - CHU Montpellier - Service de Psychiatrie Adulte; 🇫🇷 Montpellier, France

Centre Hospitalier Le Vinatier - Service de Psychiatrie Adulte; 🇫🇷 Bron, France

CHU de Clermont-Ferrand - Pôle de Psychiatrie B; 🇫🇷 Clermont-Ferrand, France

Centre Esquirol - CHU de Caen - Service de Psychiatrie Adulte,; 🇫🇷 Caen, France

CHRU de Tours - Clinique Psychiatrique Universitaire; 🇫🇷 Tours Cedex 9, France

Centre Hospitalier Saint-Anne - Service de Psychiatrie Adultes; 🇫🇷 Paris, France

Centre Hospitalier Princesse Grace - Service de Psychiatrie; 🇲🇨 Monaco, Monaco