Clinical trial NCT02744989: STIM'ZO : Examining tDCS as an add-on Treatment for Persistent Symptoms in Schizophrenia
Official title: STIM'ZO : Examining tDCS as an add-on Treatment for Persistent Symptoms in Schizophrenia (SCH)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Mental Disorders
Schizophrenia
Keywords: Schizophrenia
Transcranial direct-current stimulation (tDCS)
Sham
Positive and Negative Syndrome Scale (PANSS)
Functional Magnetic Resonance Imaging (fRMI)
Brain-Derived-Neurotrophic Factor (BDNF)
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2016-04-20
Enrollment: 141
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

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

Primary outcomes:
measure: Number of responders
timeFrame: Between baseline (day 0) and after 10-sessions of tDCS regimen (day 5)
Secondary outcomes:
measure: Positive and Negative Syndrome Scale (PANSS) score
timeFrame: Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session
measure: Auditory Hallucination Rating Scale (AHRS) score
timeFrame: Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session
measure: Psycho-Sensory hAllucinations Scale (PSAS) score
timeFrame: Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session
measure: Calgary Depression Scale for Schizophrenia (CDSS) score
timeFrame: Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session
measure: Clinical Global Impression (CGI) score
timeFrame: Baseline, day 5 (after 10-sessions of tDCS regimen), 1 month, 3 months and 6 months after the last tDCS session
measure: Shortened Quality of Life questionnaire score
timeFrame: Baseline and 6 months after the last tDCS session
measure: Scale to assess Unawareness of Mental Disorder (SUMD) score
timeFrame: Baseline and 3 months after the last tDCS session
measure: Medication Adherence rating Scale (MARS) score
timeFrame: Baseline and 3 months after the last tDCS session
measure: Brief Medication Questionnaire (BMQ) scores
timeFrame: Baseline and 3 months after the last tDCS session
measure: Source monitoring test score
timeFrame: Baseline and day 5 (after 10-sessions of tDCS regimen)
measure: Functional magnetic resonance imaging (MRI)
timeFrame: Baseline, day 5 (after 10-sessions of tDCS regimen) and 1 month after the last tDCS session
measure: Anatomical magnetic resonance imaging (MRI)
timeFrame: Baseline, day 5 (after 10-sessions of tDCS regimen) and 1 month after the last tDCS session
measure: Total serum Brain-Derived-Neurotrophic Factor (BDNF)
timeFrame: Baseline
measure: Serum Brain-Derived-Neurotrophic Factor (BDNF) isoforms
timeFrame: Baseline
measure: Self-evaluation of Negative Symptoms (SNS) score
timeFrame: Baseline, 1 month and 3 months after the last tDCS session
measure: Fargerström test score
timeFrame: Baseline, 1 month and 6 months after the last tDCS session
Other outcomes:
Locations:
city: Bron
country: France
facility: Centre Hospitalier Le Vinatier - Service de Psychiatrie Adulte
city: Caen
country: France
facility: Centre Esquirol - CHU de Caen - Service de Psychiatrie Adulte,
city: Clermont-Ferrand
country: France
facility: CHU de Clermont-Ferrand - Pôle de Psychiatrie B
city: Lille
country: France
facility: Hôpital Fontan - CHRU de Lille - Pôle de Psychiatrie
city: Lyon cedex 03
country: France
facility: Hôpital Edouard Herriot - Service d'Urgences Psychiatriques
city: Montpellier
country: France
facility: Hôpital de la Colombière - CHU Montpellier - Service de Psychiatrie Adulte
city: Paris
country: France
facility: Centre Hospitalier Saint-Anne - Service de Psychiatrie Adultes
city: Saint-Etienne Cedex 2
country: France
facility: CHU de St-Etienne - Service d'Urgences Psychiatriques
city: Tours Cedex 9
country: France
facility: CHRU de Tours - Clinique Psychiatrique Universitaire
city: Monaco
country: Monaco
facility: Centre Hospitalier Princesse Grace - Service de Psychiatrie
Study officials:
References:
citation: Brunelin J, Mondino M, Haesebaert J, Attal J, Benoit M, Chupin M, Dollfus S, El-Hage W, Galvao F, Jardri R, Llorca PM, Magaud L, Plaze M, Schott-Pethelaz AM, Suaud-Chagny MF, Szekely D, Fakra E, Poulet E. Examining transcranial random noise stimulation as an add-on treatment for persistent symptoms in schizophrenia (STIM'Zo): a study protocol for a multicentre, double-blind, randomized sham-controlled clinical trial. Trials. 2021 Dec 28;22(1):964. doi: 10.1186/s13063-021-05928-9.