fMRI-based Neurofeedback to Relieve Drug-resistant Auditory Hallucinations

NCT04798131 | Recruiting

• 3 other identifiers: 2020_082020-A00631-38WP3 UNREHAL
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

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 12 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 and re-evaluated at 2 months post-treatment. We expect significant clinical benefits from fMRI-based neurofeedback on drug-resistant hallucinations compared with the sham group.

Conditions

Schizophrenia; Hallucinations, Auditory; Hallucinations, Visual

Keywords

Schizophrenia; Hallucinations; Drug-resistance; functional MRI; Neurofeedback; Machine-Learning.

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• Change from baseline in Auditory Hallucinations Rating Scale (AHRS) measure

  1 month and 2 months after treatment

• Changes in global functioning relative to baseline

  1 month and 2 months after treatment

• Changes in quality of life relative to baseline

  1 month and 2 months after treatment

• Changes in structural MRI markers relative to baseline

  1 month and 2 months after treatment

• Changes in structural MRI markers relative to baseline

  1 month and 2 months after treatment

Study Arms (2)

Active

EXPERIMENTAL

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

Other: Active neurofeedback procedure

Sham

SHAM COMPARATOR

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

Other: Sham neurofeedback procedure

Interventions

Active neurofeedback procedure OTHER

Patients will perform 3 fMRI sessions. After one baseline fMRI run, two consecutive fMRI sessions (1/ day) during which they will continuously receive visual feedback (12 runs in total) 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. Two post-treatment visits are scheduled at 1 and 2 months to assess hallucinations severity.

Active

Sham neurofeedback procedure OTHER

Patients will perform 3 fMRI sessions. After one baseline fMRI run, two consecutive fMRI sessions (1/ day) during which they will receive a random feedback (12 runs in total). Two post-treatment visits are scheduled at 1 and 2 months with the same clinical assessment than the active group.

Sham

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Right-handed female/male between 18 to 60 y.o.
• 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

You may not qualify if:

• Refusal to participate after clear and honest information about the study has been provided
• Clinical condition incompatible with the study protocol (e.g. agitation, severe disorganization, catatonia)
• Pregnancy
• Contraindication to MRI scan: pacemaker, ferromagnetic vascular clip, ferromagnetic foreign body
• Morphological criteria: weight \>130kg, abdominal cirumference exceeding magnet aperture, shoulder width
• Claustrophobia
• Refusal to be informed of any incidental findings observed during the MRNI
• No social insurance

Sponsors & Collaborators

• University Hospital, Lille: lead
• National Research Agency, France: collaborator

Study Sites (1)

Hop Fontan Chu

Lille, France

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Hallucinations

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders; Perceptual Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Renaud JARDRI, MD,PhD

  University Hospital, Lille

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Renaud JARDRI, MD,PhD

CONTACT

0320445962; renaud.jardri@chru-lille.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: March 15, 2021
• Study Start: August 26, 2022
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028
• Last Updated: October 1, 2026

Record last verified: 2026-09

Locations

FR (1)