tDCS for Cognitive Impairment Associated With Recent-onset Schizophrenia (STICOG)

Grenoble Alpes University Hospital Center (CHU)

Status: Not yet enrolling

Conditions: Schizophrenia; Psychotic Disorder

Treatments: Device: left fronto-temporal transcranial Direct Current Stimulation (tDCS)

Study type: Interventional

Funder types: Other

Identifiers

NCT05440955

STICOG

Details and patient eligibility

About

Background: In parallel to the traditional symptomatology, deficits in cognition (memory, attention, reasoning, social functioning) contribute significantly to disability and suffering in individuals with schizophrenia. Cognitive deficits have been closely linked to alterations in early auditory processes (EAP) that occur in auditory cortical areas. Preliminary evidence indicates that cognitive deficits in schizophrenia can be improved with a reliable and safe non-invasive brain stimulation technique called tDCS (transcranial Direct Current Stimulation). However, a significant proportion of patients derive no cognitive benefits after tDCS treatment. Further, the neurobiological mechanisms of cognitive changes after tDCS have been poorly explored in trials and are thus still unclear.

Method: The study is designed as a randomized, double-blind, 2-arm parallel-group, sham controlled, 4-centers trial. Sixty participants with recent-onset schizophrenia and cognitive impairment will be randomly allocated to receive either active (n=30) or sham (n=30) tDCS (20-min, 2-mA, 10 sessions during 5 consecutive weekdays). The anode will be placed over the left dorsolateral prefrontal cortex and the cathode over the left auditory cortex. Cognition, tolerance, symptoms, general outcome and EAP (measured with EEG and multimodal MRI) will be assessed prior to tDCS (baseline), after the 10 sessions, and at 1- and 3-month follow-up. The primary outcome will be the number of responders, defined as participants demonstrating a cognitive improvement ≥Z=0.5 from baseline on the MATRICS Consensus Cognitive Battery total score at 1-month follow-up. Additionally, we will measure how differences in EAP modulate individual cognitive benefits from active tDCS and whether there are changes in EAP measures in responders after active tDCS.

Discussion: Besides proposing a new fronto-temporal tDCS protocol by targeting the auditory cortical areas, we aim to conduct an RCT with follow-up assessments up to 3-months and a large sample size. In addition, this study will allow identifying and assessing the value of a wide range of neurobiological EAP measures for predicting and explaining cognitive deficits improvement after tDCS. The results of this trial will constitute a step toward the use of tDCS as a therapeutic tool for the treatment of cognitive impairment in recent-onset schizophrenia.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 35 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

The inclusion criteria include:

1. subjects of both genders, diagnosed with recent-onset schizophrenia (first 3 years of illness), confirmed through the Structured Clinical Interview for the American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, 5th edition (SCID-5);
2. aged 18-35 years;
3. intelligence quotient (IQ) > 55;
4. cognitive deficit confirmed by a MCCB (MATRICS Cognitive Consensus Battery) total score T-score < 40;
5. the subjects should be receiving stable doses of antipsychotics for ≥ 4 weeks;
6. the subjects are covered by a public health insurance.

The exclusion criteria include:

1. pregnant (controlled by urine pregnancy test in females of childbearing age) or breastfeeding women;
2. unstable or acute medical conditions;
3. subjects who receive involuntary treatment or guardianship;
4. history of cranioencephalic trauma with loss of consciousness or central nervous system diseases that affect the brain;
5. use of drugs that affect cognitive performance such as anticholinergic agents and benzodiazepines;
6. current diagnosis of substance abuse or history of substance dependence in the last 6 months, except nicotine;
7. MRI (Magnetic Resonance Imaging), PET (Positron Emission Tomography) or tDCS (transcranial Direct Current Stimulation) contraindications

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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60 participants in 2 patient groups

active tDCS

Experimental group

Description:

tDCS (transcranial Direct Current Stimulation subjects) is a noninvasive brain stimulation technique that involves the passage of a small electric current through the scalp and skull to modulate brain activity \[10\]. The study intervention consists of ten 20-minutes sessions of active or sham tDCS. Sessions will be delivered twice daily and separated by at least 2 hours for 5 consecutive weekdays. The electric current will be generated by an electric stimulator (class IIa medical device).

Treatment:

Device: left fronto-temporal transcranial Direct Current Stimulation (tDCS)

sham tDCS

Sham Comparator group

Description:

The sham procedure is developed by the tDCS device manufacturer, which allows using the same tDCS device and the same procedure (i.e., 10 sessions delivered during five consecutive days) for both the active and sham procedures. In the sham condition, the electrodes will be placed in the same positions as in the active group; however, the stimulator will be only active for initial and final ramp up/ramp down periods, in order to mimic the sensation of active stimulation. In addition, brief pulses of 110 μA will be administered every 550 ms in order to control impedance and keep the manipulator blinded to the active or sham condition.

Treatment:

Device: left fronto-temporal transcranial Direct Current Stimulation (tDCS)