Clinical trial NCT05440955: tDCS for Cognitive Impairment Associated With Recent-onset Schizophrenia
Official title: Efficacy and Auditory Biomarker Analysis of Fronto-Temporal Transcranial Direct Current Stimulation (tDCS) in Targeting Cognitive Impairment Associated With Recent-onset Schizophrenia: A Randomized Double-blind Sham-controlled Trial
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Schizophrenia
Psychotic Disorder
Keywords: schizophrenia
cognitive impairment
tDCS
early auditory processing
clinical trial
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Direction Générale de l'Offre de Soins
First posted: 2022-07-01
Enrollment: 60
Sex: ALL
Minimum age (years): 18
Maximum age (years): 35
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The present study is designed as a superiority, double-blind, parallel-group, sham-controlled randomized clinical trial with an allocation ratio of 1:1.
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility 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

Primary outcomes:
measure: Cognitive response
timeFrame: at 1-month follow-up
Secondary outcomes:
measure: Long term cognitive response
timeFrame: at inclusion; at 3-months follow-up
measure: Cognitive domain response
timeFrame: at inclusion; at 1-month follow-up; at 3-months follow-up
measure: Clinical response 1
timeFrame: at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up
measure: Clinical response 2
timeFrame: at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up
measure: Clinical response 3
timeFrame: at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up
measure: Clinical response 4
timeFrame: at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up
measure: Clinical response 5
timeFrame: at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up
measure: Clinical response 6
timeFrame: at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up
measure: Clinical response 7
timeFrame: at inclusion; at 1-week; at 1-month follow-up; at 3-months follow-up
measure: Outcome response 1
timeFrame: at inclusion; at 1-month follow-up; at 3-months follow-up
measure: Outcome response 2
timeFrame: at inclusion; at 1-month follow-up; at 3-months follow-up
measure: Tolerance 1
timeFrame: at 1-week
measure: Tolerance 2
timeFrame: at 1-week
measure: Response marker 1
timeFrame: at inclusion
measure: Response marker 2
timeFrame: at inclusion
measure: Response marker 3
timeFrame: at inclusion
measure: Response marker 4
timeFrame: at inclusion
measure: Response marker 5
timeFrame: at inclusion
measure: Response predictor 1
timeFrame: at inclusion; at 1-month follow-up
measure: Response predictor 2
timeFrame: at inclusion; at 1-month follow-up
measure: Response predictor 3
timeFrame: at inclusion; at 1-month follow-up
measure: Response predictor 4
timeFrame: at inclusion; at 1-month follow-up
measure: Response predictor 5
timeFrame: at inclusion; at 1-month follow-up
measure: Response predictor 6
timeFrame: at inclusion; at 1-month follow-up
Other outcomes:
Locations:
city: La Tronche
country: France
facility: CHU Grenoble Alpes
state: Auvergne-Rhône-Alpes
city: Saint-Égrève
country: France
facility: CH Alpes-Isère
state: Rhône-Alpes
city: Bron
country: France
facility: CH Le Vinatier
city: Saint-Étienne
country: France
facility: CHU Saint-Etienne
Study officials:
affiliation: CHU Grenoble Alpes
name: Clément DONDÉ
role: PRINCIPAL_INVESTIGATOR
References: