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

NCT02744989 | Completed

• 1 other identifier: 69HCL14_0446
• Study Type: interventional
• Target: 141
• Locations: 2 countries
• Sites: 10

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.

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)

Outcome Measures

Primary Outcomes (1)

• Number of responders

  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.

  Between baseline (day 0) and after 10-sessions of tDCS regimen (day 5)

Secondary Outcomes (16)

• 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

• 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

• 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

• 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

• 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

Study Arms (2)

Active tDCS

EXPERIMENTAL

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.

Device: Neuroconn or Neuroelectric tDCS stimulator

Sham tDCS

SHAM COMPARATOR

Device: Sham tDCS

Interventions

Neuroconn or Neuroelectric tDCS stimulator DEVICE

Stimulation parameters were chosen in conformity with those for the treatment of schizophrenic symptoms (Brunelin et al, 2012), adapted according to the latest data from the literature and the tDCS operating stimulator. The experimental tDCS group will receive the ACTIVE stimulation with the following parameters: oscillatory Direct Current with high frequency random noise stimulation (hf-tRNS - 100 to 500 Hz), Intensity = 2 mA, offset = + 1 mA, seance duration = 20 minutes ramp up/ramp down 30 seconds. Total number of sessions = 10 (sessions twice daily for 5 days separated by at least 2 hours for 5 consecutive weekdays).

Active tDCS

Sham tDCS DEVICE

The control group will receive the SHAM stimulation (placebo) following the same regimen (i.e., twice daily sessions separated by at least 2 hours for 5 consecutive weekdays). Sham stimulation consists of a 20 minutes session including 40 seconds of active stimulation (same parameters as in the ACTIVE arm) at the beginning of the sessions, whatever the stimulator

Sham tDCS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of schizophrenia according to DSM 5.0 (Diagnostic and Statistical Manuel 5.0) criteria
• 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,
• Patient under curatorship/guardianship or not
• Age between 18 and 65 years old.
• Covered by, or having the right to Social Security
• Patient who understands the French language
• Informed consent signed

You may not qualify if:

• 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).
• Contraindications for tDCS (neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes),
• Increase in total composite PANSS score of at least 20% between screening and enrollment visits
• Women who are pregnant
• Patients whose clinical condition requires in patient procedure under constraint

Sponsors & Collaborators

• Hospices Civils de Lyon: lead

Study Sites (10)

Centre Hospitalier Le Vinatier - Service de Psychiatrie Adulte

Bron, 69678, France

Location

Centre Esquirol - CHU de Caen - Service de Psychiatrie Adulte,

Caen, 14033, France

Location

CHU de Clermont-Ferrand - Pôle de Psychiatrie B

Clermont-Ferrand, 63000, France

Location

Hôpital Fontan - CHRU de Lille - Pôle de Psychiatrie

Lille, 59037, France

Location

Hôpital Edouard Herriot - Service d'Urgences Psychiatriques

Lyon, 69437, France

Location

Hôpital de la Colombière - CHU Montpellier - Service de Psychiatrie Adulte

Montpellier, 34295, France

Location

Centre Hospitalier Saint-Anne - Service de Psychiatrie Adultes

Paris, 75014, France

Location

CHU de St-Etienne - Service d'Urgences Psychiatriques

Saint-Etienne, 42055, France

Location

CHRU de Tours - Clinique Psychiatrique Universitaire

Tours, 37044, France

Location

Centre Hospitalier Princesse Grace - Service de Psychiatrie

Monaco, 98000, Monaco

Location

Related Publications (1)

• 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.

  PMID: 34963486 RESULT

MeSH Terms

Conditions

Mental Disorders; Schizophrenia

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2016
• First Posted: April 20, 2016
• Study Start: May 30, 2016
• Primary Completion: May 1, 2022
• Study Completion: October 19, 2022
• Last Updated: December 19, 2025

Record last verified: 2025-12

Locations

FR (9); MO (1)