HD-tDCS for Hallucinations (TARGET)

Targeting Multimodal Hallucinations With fMRI-guided High-definition Transcranial Direct Current Stimulation (HD-tDCS) in Schizophrenia

One in three patients with schizophrenia experiences hallucinations that are refractory to conventional pharmacotherapy. For refractory auditory hallucinations, transcranial direct current stimulation -tDCS- has been proposed as a novel therapeutic approach. Although promising beneficial effects on auditory hallucinations have been found by targeting the left frontal and temporoparietal cortex, the high variability observed in clinical response leaves much room for optimizing stimulation parameters. For instance, options should go beyond the left temporoparietal junction as a unique and single target of hallucinations, taking into account the personalization of the targeting based on the actual brain networks involved in hallucinations, including those beyond the auditory modality, as well as multimodal hallucinations.

The present study will take advantage of recent technological developments to propose a personalized therapeutic strategy to alleviate hallucinations in schizophrenia. This will involve:

• the simultaneous targeting of multiple brain regions with High-Definition (HD)-tDCS, which is known for its precise and longer-lasting effects compared to conventional tDCS.
• and the fMRI-capture of hallucinations, using a precise and reliable data-driven approach to identify the functional brain networks recruited during hallucinations.

The aim of the study is to assess whether repeated sessions of HD-tDCS guided using the fMRI capture of hallucinations can reduce multimodal hallucinations in patients with schizophrenia, compared to sham sessions of HD-tDCS.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia; Hallucinations
• Intervention / Treatment: Procedure: High-definition transcranial direct current (HD-tDCS), active condition; Procedure: High-definition transcranial direct current (HD-tDCS), sham condition

Detailed Description

The study is a multicentre, prospective, randomised, double-blind, parallel group, sham-controlled, two-arm clinical trial. Arm one is repeated active HD-tDCS guided using the fMRI-capture of hallucinations (20 sessions of stimulation over 10 days, 20 min/session). Arm two is the blinded sham repeated HD-tDCS guided by the fMRI-capture of hallucinations (20 sessions of sham stimulation over 10 days, 20 min/session).

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Marine Mondino; Phone Number: +33 04.37.91.15.65; Email: marine.mondino@ch-le-vinatier.fr
• Study Contact Backup: Name: Jérôme Brunelin; Phone Number: +33 04.37.91.55.65; Email: Jerome.brunelin@ch-le-vinatier.fr

Study Locations

• France
  • Bron, France, 69678
    • Centre Hospitalier le Vinatier

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Females and males aged between 18 and 50
• Diagnosis of schizophrenia according to DSM 5.0 criteria
• Presence of dailyfrequent hallucinations (> 2 / hour) despite the optimization of the antipsychotic dosage and molecule (based on the prescriber's judgment) for at least 6 weeks. The presence of such daily frequent refractory hallucinations will be operationalized by an interview with a trained psychiatrist.
• Patient under curatorship/guardianship or not
• Covered by a public health insurance
• Understanding French language
• Signed written informed consent after being informed about the study

Exclusion Criteria:

• Other disabling Axis Inpsychiatric conditions including a current diagnosis of a major depressive episode (uni- or bi- polar disorder) according to DSM 5, and substance use disorder (except tobacco)
• Use of hallucinogenic drugs
• Contraindications for magnetic resonance imaging or tDCS (neurologic stimulator, pacemaker, cardiac defibrillator, cardiac prosthesis, vascular prosthesis, intracranial clips or clamps, cerebrospinal fluid derivation, metallic splinters in the eyes, cochlear implants, severe claustrophobia)
• Changes in the total PSAS and PANSS score of at least 15% between screening/inclusion (T0) and baseline visits (T1). This criterion will ensure the stability of symptoms before treatment.
• Pregnancy (controlled by urine pregnancy test in women of childbearing potential) or breastfeeding
• A clinical condition requiring inpatient procedure under constraint

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: active stimulation group; 23 patients will receive 20 sessions of active HD-tDCS	Procedure: High-definition transcranial direct current (HD-tDCS), active condition; Patients will receive 20 sessions of active HD-tDCS for a duration of 20min. Sessions will be delivered twice-daily over 2 weeks on the 5 consecutive working days. The number of electrodes used, electrode placement on the scalp (based on EEG 10/10), and the individual currents that need to be injected from each electrode will be determined based on the brain networks identified as involved in their hallucinations during a fMRI acquisition performed at baseline, and computed using a neurotargeting software that allows determining optimal electrode montages for achieving maximal brain current flow in the targeted brain region.
Placebo Comparator: placebo stimulation group; High-definition transcranial direct current (HD-tDCS), sham condition	Procedure: High-definition transcranial direct current (HD-tDCS), sham condition; Participants will receive 20 sessions of sham HD-tDCS, which will be delivered following the same procedures as active HD-tDCS. However, stimulation will only be administered in the initial 30 seconds of the 20-minute period, with no further stimulation during the remaining duration. This approach aims to replicate the tingling sensation commonly associated with active stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in hallucinations	Comparison between the active HD-tDCS group and the sham HD-tDCS group of the change in multimodal hallucinations between baseline (V1, within 1 week before the first HD-tDCS session) and after the 20 HD-tDCS sessions (V2, within 1 week of the last HD-tDCS session). Change in hallucinations will be measured as the percentage change in score on the Psychosensory Hallucination Scale	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Long-term changes in hallucinations	Comparisons between active and sham HD-tDCS groups of the change in multimodal hallucinations (assessed with the PSAS, in percent) between baseline and follow-up assessments at one month and three months after the 20 sessions of HD-tDCS.	6 months
Change in symptoms of schizophrenia	Comparisons between active and sham HD-tDCS groups of the change in other symptoms of schizophrenia between baseline (V1, within 1 week before first stimulation) and post-intervention (V2, within 1 week after last stimulation), and follow-up assessments (V3: at one month, V4: at 3 months). Symptoms of schizophrenia will be measured by the total score at the Positive and Negative Syndrome Scale - PANSS , and by the scores in the five subdimensions of the PANSS (positive, negative, depression, disorganization, and grandiosity/excitement).	6 months
Change in social functioning	Comparisons between active and sham HD-tDCS groups of change in social functioning measured by the Social and Occupational Functioning Assessment Scale - SOFAS (Goldman et al., 1992) between baseline (V1, within 1 week before first stimulation) and follow-up assessments, one month (V3) and three months (V4) after the intervention	6 months
Changes in source-monitoring performance	Source monitoring performance will be evaluated using a specific source monitoring task. Source-monitoring accuracy scores (range 0-100) will be calculated as proportions of accurate source attributions for each source	6 months
Changes in brain connectivity	Comparisons between active and sham HD-tDCS groups of changes in brain connectivity within the hallucination-related network, measured with fMRI	6 months

Collaborators and Investigators

• Sponsor: Hôpital le Vinatier

Study record dates

Study Major Dates

• Study Start (Estimated): February 28, 2024
• Primary Completion (Estimated): February 28, 2028
• Study Completion (Estimated): July 30, 2028

Study Registration Dates

• First Submitted: December 12, 2023
• First Submitted That Met QC Criteria: January 4, 2024
• First Posted (Actual): January 17, 2024

Study Record Updates

• Last Update Posted (Actual): January 17, 2024
• Last Update Submitted That Met QC Criteria: January 4, 2024
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Keywords: schizophrenia; fMRI; non-invasive brain stimulation; HD-tDCS; hallucinations
• Additional Relevant MeSH Terms: Mental Disorders; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Schizophrenia Spectrum and Other Psychotic Disorders; Perceptual Disorders; Schizophrenia; Hallucinations
• Other Study ID Numbers: 2023-A01629-36

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No