INTRUDE: fMRI-based Neurofeedback to Relieve Drug-resistant Auditory Hallucinations

Sponsor

University Hospital, Lille (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04798131

Collaborator

National Research Agency, France (Other)

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

The INTRUDE trial aims at assessing the efficacy of an fMRI-based neurofeedback procedure on drug-resistant auditory hallucinations. Hallucinations are complex and transient mental states associated with subtle and brain-wide patterns of activity for which we were recently able to validate an fMRI multivariate decoder. Based on this progress, we can track patients' hallucinatory status using real-time fMRI. We will test whether schizophrenia patients with drug-resistant hallucinations can be trained to maintain the brain state associated with a no-hallucination condition using appropriate strategies and thus reduce overall severity. We will refer to a double-blind randomized placebo-controlled design. A total of 86 patients will be enrolled and equally split in an active neurofeedback group (n=43) and a sham group (n=43), matched for sex, age and PANSS scores. Each patient will benefit from 4 runs of either active or sham neurofeedback. The primary outcome measure will be the mean decrease of AHRS scores relative to baseline, and at 1 month post-treatment. We expect significant clinical benefits from fMRI-based neurofeedback on drug-resistant hallucinations compared with the sham group.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia Hallucinations, Auditory Hallucinations, Visual	Other: Active neurofeedback procedure Other: Sham neurofeedback procedure	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

84 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

Treat Refractory Auditory Hallucinations in Schizophrenia Patients With fMRI-guided Neurofeedback: a Randomized-controlled Trial

Anticipated Study Start Date :

Dec 1, 2022

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active The visual feedback will correspond to instructions, adapted to the current hallucinatory state and decoded online from the fMRI signal.	Other: Active neurofeedback procedure Patients will perform 5 fMRI sessions. Four consecutive fMRI runs (1/ day) during which they will continuously receive visual feedback computed from the fMRI signal analyzed with the hallucinations decoder. Patients will be trained to maintain the brain state associated with the no-hallucination state using appropriate coping strategies. A 5th fMRI scan will be performed at 1 month post-treatment.
Sham Comparator: Sham The visual feedback will correspond to random instructions independently of the fMRI signal.	Other: Sham neurofeedback procedure Patients will perform 5 fMRI sessions. Four consecutive fMRI runs (1/ day) during which they will receive a random feedback and a 5th run at 1 month post-treatment.

Arm

Intervention/Treatment

Experimental: Active

The visual feedback will correspond to instructions, adapted to the current hallucinatory state and decoded online from the fMRI signal.

Other: Active neurofeedback procedure

Patients will perform 5 fMRI sessions. Four consecutive fMRI runs (1/ day) during which they will continuously receive visual feedback computed from the fMRI signal analyzed with the hallucinations decoder. Patients will be trained to maintain the brain state associated with the no-hallucination state using appropriate coping strategies. A 5th fMRI scan will be performed at 1 month post-treatment.

Sham Comparator: Sham

The visual feedback will correspond to random instructions independently of the fMRI signal.

Other: Sham neurofeedback procedure

Patients will perform 5 fMRI sessions. Four consecutive fMRI runs (1/ day) during which they will receive a random feedback and a 5th run at 1 month post-treatment.

Outcome Measures

Primary Outcome Measures

Change from baseline in the Auditory Hallucination Rating Scale (AHRS) measure of hallucinations severity [1 month after treatment]
AHRS will be measured at t0 (randomization) and at 1 month after treatment Minimum score is 2, maximum score is 41, higher score indicates more severe symptoms.

Secondary Outcome Measures

Change from baseline in Positive and Negative Syndrome Scale (PANSS) measure of hallucinations severity [1 month after treatment]
PANSS will be measured at t0 (randomization) and at 1 month after treatment The PANSS contains 7 positive symptom scales, 7 negative system scales, and 16 general psychopathology symptom scales. rate from 1 to 7 on each symptom scale. The total score is the sum of all scales with a minimum score of 30 and a maximum score of 210
Change from baseline Questionnaire for Psychotic Experiences (QPE) measure for severity of hallucinations [1 month after treatment]
QPE will be measured at t0 (randomization) and at 1 month after treatment
Change from baseline Simplified Acute Physiology Score (SAPS) measure for severity of hallucinations [1 month after treatment]
SAPS will be measured at t0 (randomization) and at 1 month after treatment
Change from baseline Visual analogue scale (VAS) measure for severity of hallucinations [1 month after treatment]
VAS will be measured at t0 (randomization) and at 1 month after treatment
Changes in global functioning relative to baseline [1 month after treatment]
Global Assessment of Functioning (GAF) is a numeric scale be measured at t0 (randomization) and at 1 month after treatment Scores range from 100 (extremely high functioning) to 1 (severely impaired).
Changes in quality of life relative to baseline [1 month after treatment]
SQLS score will be measured at t0 (randomization) and at 1 month after treatment
Changes in structural MRI markers relative to baseline [1 month after treatment]
Cortical thickness will be measured at t0 (randomization) and at 1 month after treatment
Changes in structural MRI markers relative to baseline [1 month after treatment]
Gyrification Index will be measured at t0 (randomization) and at 1 month after treatment
Changes in functional MRI markers relative to baseline [1 month after treatment]
Brain activity at rest and connectivity metrics will be measured at t0 (randomization) and at 1 month after treatment