fMRI-based Neurofeedback to Relieve Drug-resistant Auditory Hallucinations (INTRUDE)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Schizophrenia; Hallucinations, Auditory; Hallucinations, Visual
• Intervention / Treatment: Other: Active neurofeedback procedure; Other: Sham neurofeedback procedure

• Study Type: Interventional
• Enrollment (Anticipated): 84
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Renaud JARDRI, MD,PhD; Phone Number: +33 0320445962; Email: renaud.jardri@chru-lille.fr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Schizophrenia (according to the DSM-5 classification)
• Frequent auditory hallucinations (SAPS item #1 ≥ 4)
• Stable medication for at least 30 days
• Absence of chronic neurological disorder (including seizure)
• Able to provide free written consent to participate in the research

Exclusion Criteria:

• Pregnancy
• Contraindication to MRI scan
• Claustrophobia
• No social insurance

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Auditory Hallucination Rating Scale (AHRS) measure of hallucinations severity	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.	1 month after treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in Positive and Negative Syndrome Scale (PANSS) measure of hallucinations severity	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	1 month after treatment
Change from baseline Questionnaire for Psychotic Experiences (QPE) measure for severity of hallucinations	QPE will be measured at t0 (randomization) and at 1 month after treatment	1 month after treatment
Change from baseline Simplified Acute Physiology Score (SAPS) measure for severity of hallucinations	SAPS will be measured at t0 (randomization) and at 1 month after treatment	1 month after treatment
Change from baseline Visual analogue scale (VAS) measure for severity of hallucinations	VAS will be measured at t0 (randomization) and at 1 month after treatment	1 month after treatment
Changes in global functioning relative to baseline	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).	1 month after treatment
Changes in quality of life relative to baseline	SQLS score will be measured at t0 (randomization) and at 1 month after treatment	1 month after treatment
Changes in structural MRI markers relative to baseline	Cortical thickness will be measured at t0 (randomization) and at 1 month after treatment	1 month after treatment
Changes in structural MRI markers relative to baseline	Gyrification Index will be measured at t0 (randomization) and at 1 month after treatment	1 month after treatment
Changes in functional MRI markers relative to baseline	Brain activity at rest and connectivity metrics will be measured at t0 (randomization) and at 1 month after treatment	1 month after treatment

Collaborators and Investigators

• Sponsor: University Hospital, Lille
• Collaborators: National Research Agency, France
• Investigators: Principal Investigator: Renaud JARDRI, MD,PhD, University Hospital, Lille

Study record dates

Study Major Dates

• Study Start (Anticipated): December 1, 2022
• Primary Completion (Anticipated): July 1, 2026
• Study Completion (Anticipated): July 1, 2026

Study Registration Dates

• First Submitted: January 14, 2021
• First Submitted That Met QC Criteria: March 11, 2021
• First Posted (Actual): March 15, 2021

Study Record Updates

• Last Update Posted (Actual): March 25, 2022
• Last Update Submitted That Met QC Criteria: March 24, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Keywords: Schizophrenia; functional MRI; Neurofeedback; Drug-resistance; Hallucinations; Machine-Learning.
• 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: 2020_08; 2020-A00631-38 (Other Identifier: ID-RCB number,ANSM); ANR-16-CE37-0015 (Other Identifier: ANR number)

Drug and device information, study documents

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