tDCS for Cognitive Impairment Associated With Recent-onset Schizophrenia

NCT ID: NCT05440955

Last Updated: 2023-04-04

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-06-01
• Study Completion Date: 2027-06-01

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.

Conditions

Schizophrenia; Psychotic Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

active tDCS

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).

Group Type: EXPERIMENTAL

left fronto-temporal transcranial Direct Current Stimulation (tDCS)

Intervention Type: DEVICE

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). During the entire tDCS session, the subject is at "rest", comfortably seated in a chair in a quiet room. A clinician will be present for the entire session duration. The current will be applied via a pair of rubber electrodes (35 cm²) placed on the surface of the scalp. The anode will be placed over the left dorsolateral prefrontal cortex. The cathode will be placed over the left auditory cortex. The stimulation parameters will be set at 2-mA for 20 minutes, with a progressive increase during the first 30-sec and a progressive decrease during the last 30-sec of each session. The impedance of the applied current is monitored by the stimulator during each session.

sham tDCS

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.

Group Type: SHAM_COMPARATOR

left fronto-temporal transcranial Direct Current Stimulation (tDCS)

Intervention Type: DEVICE

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). During the entire tDCS session, the subject is at "rest", comfortably seated in a chair in a quiet room. A clinician will be present for the entire session duration. The current will be applied via a pair of rubber electrodes (35 cm²) placed on the surface of the scalp. The anode will be placed over the left dorsolateral prefrontal cortex. The cathode will be placed over the left auditory cortex. The stimulation parameters will be set at 2-mA for 20 minutes, with a progressive increase during the first 30-sec and a progressive decrease during the last 30-sec of each session. The impedance of the applied current is monitored by the stimulator during each session.

Interventions

left fronto-temporal transcranial Direct Current Stimulation (tDCS)

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). During the entire tDCS session, the subject is at "rest", comfortably seated in a chair in a quiet room. A clinician will be present for the entire session duration. The current will be applied via a pair of rubber electrodes (35 cm²) placed on the surface of the scalp. The anode will be placed over the left dorsolateral prefrontal cortex. The cathode will be placed over the left auditory cortex. The stimulation parameters will be set at 2-mA for 20 minutes, with a progressive increase during the first 30-sec and a progressive decrease during the last 30-sec of each session. The impedance of the applied current is monitored by the stimulator during each session.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

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.

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 35 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Direction Générale de l'Offre de Soins

OTHER_GOV

Sponsor Role: collaborator

University Hospital, Grenoble

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Clément DONDÉ

Role: PRINCIPAL_INVESTIGATOR

CHU Grenoble Alpes

Locations

CHU Grenoble Alpes

La Tronche, Auvergne-Rhône-Alpes, France

CH Alpes-Isère

Saint-Égrève, Auvergne-Rhône-Alpes, France

CH Le Vinatier

Bron, , France

CHU Saint-Etienne

Saint-Etienne, , France

Countries

France

Central Contacts

Julien COLOMBAT

Role: CONTACT

jcolombat@chu-grenoble.fr

04 76 76 56 09

Facility Contacts

Colombat Julien

Role: primary

jcolombat@chu-grenoble.fr

04 76 76 56 09

Julien COLOMBAT

Role: primary

jcolombat@chu-grenoble.fr

04 76 76 56 09

Lydie Sartelet

Role: primary

lydie.sartelet@ch-le-vinatier.fr

Hélène RINGARD

Role: primary

helene.raingard@chu-st-etienne.fr

04.77.82.97.03

References

Donde C, Bastin J, Pouchon A, Costes N, Fakra E, Galvao F, Gay A, Haesebaert F, Lamalle L, Merida I, Rigon M, Schneider F, Tropres I, Brunelin J, Polosan M. Efficacy and auditory biomarker analysis of fronto-temporal transcranial direct current stimulation (tDCS) in targeting cognitive impairment associated with recent-onset schizophrenia: study protocol for a multicenter randomized double-blind sham-controlled trial. Trials. 2023 Feb 24;24(1):141. doi: 10.1186/s13063-023-07160-z.

Reference Type: DERIVED

PMID: 36829240 (View on PubMed)

Other Identifiers

STICOG

Identifier Type: -

Identifier Source: org_study_id