Reduction of Auditory-Verbal Hallucinations in Schizophrenia Through Cortical Neuromodulation

Summary

Approximately 1% of the general population will be affected by schizophrenia over the course of their lives, with life expectancy being reduced by 20 years on average and quality of life being severely diminished in affected individuals. One third of patients suffering from schizophrenia will evolve towards a resistant form of the disease, amongst which many will suffer from auditory-verbal hallucinations (AVH) that current therapeutic approaches struggle to alleviate. Previous work from our team has demonstrated the possibility of robustly inferring the periods of occurrence of AVH from fMRI data, paving the way for the development of a closed-loop neuromodulation system comprised of an electrode array positioned in Broca's area, which would detect AVH in real time, and effector electrodes which would stimulate the temporo-parietal cortex to interrupt them. The aim of this project is to assess the feasibility of this system. To do so, we will first test the ability of transcranial magnetic stimulation of the "continuous theta burst" (cTBS) type, applied at the time of AVH onset, to reduce their duration and intensity, and assess whether this is associated with therapeutic response to the current gold standard rTMS protocol for AVH reduction through neuroplasticity induction. Demonstrating the feasibility of acute suppression of AVH by cortical neurostimulation is an essential element in the feasibility of a closed-loop reactive neuromodulation system.

The research project comprises two phases:

-Phase 1: randomized controlled clinical trial (1 weekly session per patient over 12 weeks: 6 active stimulation sessions and 6 sham sessions) evaluating the phasic effects of rTMS on AVHs as they appear during the sessions.

Phase 2: open-label study offering patients a routine rTMS protocol which has demonstrated its effects on AVH (10 TMS sessions over one workweek - twice daily with 1-hour intervals, MULTIMODHAL study, NCT01373866).

Conditions

• Treatment Resistant Schizophrenia

Interventions

DEVICE

Active Transcranial Magnetic Stimulation (TMS)

Active rTMS (continuous theta burst, cTBS) applied to the temporo-parietal junction (TPJ) at the onset of the Auditory Verbal Hallucinations (AVH).

DEVICE

Sham Transcranial Magnetic Stimulation (TMS)

Sham rTMS (continuous theta burst, cTBS) applied to the temporo-parietal junction (TPJ) during the onset of the Auditory Verbal Hallucinations (AVH). An electrical stimulator is synchronised with the magnetic stimulation to recreate the tactile sensation and the coils emits the same noise during sham stimulation as in the active configuration, making it impossible to distinguish between active and placebo magnetic stimulation.

Sponsors & Collaborators

• Centre Hospitalier St Anne

  lead OTHER

Principal Investigators

• Philippe Domenech, MD, PhD · GHU Paris Psychiatry & Neurosciences

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

CROSSOVER

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2024-05-21

Primary Completion

2026-05-31

Completion

2026-05-31

Countries

• France

Study Locations