HD-tDCS for Hallucinations

Schizophrenia Clinical Trial

— TARGET  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06208176
• Other study ID #: 2023-A01629-36
• Status: Not yet recruiting
• Phase: N/A
• Start date: February 28, 2024
• Est. completion date: July 30, 2028

Study information

• Verified date: December 2023
• Source: Hôpital le Vinatier
• Contact: Marine Mondino
• Phone: 04.37.91.15.65
• Email: marine.mondino[@]ch-le-vinatier.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 46
• Est. completion date: July 30, 2028
• Est. primary completion date: February 28, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 50 Years

Eligibility

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

Related Conditions & MeSH terms

• Hallucinations
• Schizophrenia

Intervention

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.
• 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.

Locations

Country	Name	City	State
France	Centre Hospitalier le Vinatier	Bron

Sponsors (1)

Lead Sponsor	Collaborator
Hôpital le Vinatier

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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