SchizophreniaNCT05299749
Real-time fMRI Neurofeedback in Patients With Schizophrenia and Auditory Hallucinations
A study testing stg-rt-fMRI-Neurofeeback in people with Schizophrenia and Auditory Hallucination, run by Boston VA Research Institute, Inc. at 1 site in United States.
Trial summary
Neurofeedback intervention aimed to regulate the superior temporal gyrus (STG) activation and default mode network (DMN) connectivity as well as to reduce the auditory hallucinations (AH) schizophrenia patients with medication resistant AH. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Schizophrenia, Auditory Hallucination, Treatment-resistant Schizophrenia
- What is being tested?
- stg-rt-fMRI-Neurofeeback
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 104 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2022to 30 Jun 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- patients diagnosed with SZ or schizoaffective disorder using DSM-5 criteria
- auditory hallucinations not responsive to pharmacology as determined by chart review and a clinical interview of SCID.
Who cannot join
- neurologic illness
- major head trauma
- electroconvulsive therapy
- alcohol or drug dependence
- alcohol or drug abuse within the past five years
- verbal IQ below 70
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
Boston VA Healthcare System, Brockton
Brockton, Massachusetts, 02301
Mia Kriksciun, BA, 774 826 1507, mia.kriksciun@va.gov
About this study
Official title: Real-time fMRI Neurofeedback as a Tool to Mitigate Auditory Hallucinations in Patients With Schizophrenia - R33 Phase
Neurofeedback intervention aimed to regulate the superior temporal gyrus (STG) activation and default mode network (DMN) connectivity as well as to reduce the auditory hallucinations (AH) schizophrenia patients with medication resistant AH.
Read the detailed description
Here, the investigators propose that neurofeedback aimed to regulate the superior temporal gyrus (STG) activation will not only lead to activation changes in the STG, but also to changes in the default mode network (DMN), as well as to reductions in AH, and that the brain and clinical changes will be correlated. The theoretical framework for the current proposal is an AH model that assumes that AH result from abnormalities in a network of regions including STG, and medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), the two latter regions are core medial hubs of DMN that are related to self-referential processing. This model is supported by several theoretical papers and experimental evidence well as preliminary data by the investigators (PD). In both R61 and R33 the investigators will study SZ patients with medication resistant AH in the rt-fMRI intervention arm and in the sham-rt-fMRI arm. In both arms, the task and the rt-fMRI session structure will be identical. The SZ-intervention group will receive feedback from the STG while SZ-sham group will receive feedback from the motor cortex. In addition, 2 functional fMRI tasks will examine the effect of rt-fMRI neurofeedback and of sham-rt-fMRI on brain response. This R33 phase will consist of an SZ-intervention group (random n=52) that will receive 5 sessions of rt-fMRI feedback targeting STG, while SZ-sham group (random n=52) will receive 5 sham-rt-fMRI sessions. Based on our R61 phase data, the investigators predict that rt-fMRI feedback aimed at STG will reduce AH which will be, in turn, associated with reductions in the STG activation and in the DMN connectivity (i.e., brain changes achieved in R61 and replicated in R33) in SZ- intervention group only. Five sessions of rt-fMRI feedback will address the question of dose response at brain and clinical levels. The impact of rt-fMRI neurofeedback and of sham-rt-fMRI on AH (primary outcome), and on delusions, negative symptoms and working memory (WM) (exploratory outcome) will be assessed with clinical and neuropsychological measures. In an exploratory aim, based on the existing literature, the investigators predict the improvement in delusions, negative symptoms and in WM score, only post-rt-fMRI neurofeedback targeting the STG and not post-sham-rt-fMRI.
- Being tested
- stg-rt-fMRI-Neurofeeback, sham-rt-fMRI-Neurofeedback
- Keywords
- Auditory-Hallucination, Connectivity, brain-activity, default-mode-network, superior temporal gyrus, Neurofeedback, MRI
- Medical subject headings
- Schizophrenia, Hallucinations, Schizophrenia, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stg-rt-fMRI-NeurofeebackOther
the patients will receive real-time feedback from the brain activity of the superior temporal gyrus
sham-rt-fMRI-NeurofeedbackOther
the patients will receive real-time feedback from the brain activity of the somato-motor cortex
| Study group | Role | What they receive |
|---|---|---|
| stg-rt-fMRI | Experimental | will receive feedback from the STG Receives: Other: stg-rt-fMRI-Neurofeeback |
| sham-rt-fMRI | Sham comparator | will receive feedback from the motor cortex Receives: Other: sham-rt-fMRI-Neurofeedback |
What is being measured
The primary outcome is the main question the study is designed to answer.
percent change in the STG BOLD signal, post- relative to pre-NFB
does real-time fMRI neurofidback reduce BOLD activity in STG, post NFB
Measured: 0-4 weeks post intervention
Secondary outcomes (2)
reduction in scores on Psychotic Symptoms Rating Scale, post- relative to pre, NFB
does real-time fMRI neurofidback reduce auditory hallucinations, post NFB
Measured: 0-4 weeks post intervention
percent change in the MPFC-PCC connectivity measure, post- relative to pre-NFB.
Does real time NFB reduce connectivity in MPFC-PCC, post NFB
Measured: 0-4 weeks post intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Mar 2022
- Study start1 Mar 2022
- Primary completion30 Jun 2026 (estimated)
- Study completion30 Jun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 104 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Boston VA Research Institute, Inc.
- Sponsor type
- University, hospital or other
- Collaborators
- Mclean Hospital, Northeastern University, Cambridge Health Alliance
- Responsible party
- Principal investigator, Margaret Niznikiewicz, Boston VA Research Institute, Inc.
- Investigators
- margaret niznikiewicz, Principal investigator, Boston VA Research Institute, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05299749
- Sponsor's protocol ID
- 4R33MH113751-03
- Status last verified
- Sep 2025
- First submitted
- 8 Mar 2022
- Last updated
- 18 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The Clinical, Cognitive and Imaging data will be made publicly available
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Real-time fMRI Neurofeedback as a Tool to Mitigate Auditory Hallucinations in Patients With Schizophrenia - R33 Phase
- ClinicalTrials.gov ID
- NCT05299749
- Acronym / sponsor ID
- 4R33MH113751-03
- Keywords
- Auditory-Hallucination, Connectivity, brain-activity, default-mode-network, superior temporal gyrus, Neurofeedback, MRI
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 104 participants (estimated)
- Lead sponsor
- Boston VA Research Institute, Inc.University, hospital or other
- Collaborators
- Mclean Hospital, Northeastern University, Cambridge Health Alliance
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 30 Jun 2026 (estimated)
- Study completion
- 30 Jun 2026 (estimated)
- First posted
- 29 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Neurofeedback intervention aimed to regulate the superior temporal gyrus (STG) activation and default mode network (DMN) connectivity as well as to reduce the auditory hallucinations (AH) schizophrenia patients with medication resistant AH.
Detailed description
Here, the investigators propose that neurofeedback aimed to regulate the superior temporal gyrus (STG) activation will not only lead to activation changes in the STG, but also to changes in the default mode network (DMN), as well as to reductions in AH, and that the brain and clinical changes will be correlated. The theoretical framework for the current proposal is an AH model that assumes that AH result from abnormalities in a network of regions including STG, and medial prefrontal cortex (MPFC) and posterior cingulate cortex (PCC), the two latter regions are core medial hubs of DMN that are related to self-referential processing. This model is supported by several theoretical papers and experimental evidence well as preliminary data by the investigators (PD). In both R61 and R33 the investigators will study SZ patients with medication resistant AH in the rt-fMRI intervention arm and in the sham-rt-fMRI arm. In both arms, the task and the rt-fMRI session structure will be identical. The SZ-intervention group will receive feedback from the STG while SZ-sham group will receive feedback from the motor cortex. In addition, 2 functional fMRI tasks will examine the effect of rt-fMRI neurofeedback and of sham-rt-fMRI on brain response. This R33 phase will consist of an SZ-intervention group (random n=52) that will receive 5 sessions of rt-fMRI feedback targeting STG, while SZ-sham group (random n=52) will receive 5 sham-rt-fMRI sessions. Based on our R61 phase data, the investigators predict that rt-fMRI feedback aimed at STG will reduce AH which will be, in turn, associated with reductions in the STG activation and in the DMN connectivity (i.e., brain changes achieved in R61 and replicated in R33) in SZ- intervention group only. Five sessions of rt-fMRI feedback will address the question of dose response at brain and clinical levels. The impact of rt-fMRI neurofeedback and of sham-rt-fMRI on AH (primary outcome), and on delusions, negative symptoms and working memory (WM) (exploratory outcome) will be assessed with clinical and neuropsychological measures. In an exploratory aim, based on the existing literature, the investigators predict the improvement in delusions, negative symptoms and in WM score, only post-rt-fMRI neurofeedback targeting the STG and not post-sham-rt-fMRI.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| stg-rt-fMRI | Experimental | Other: stg-rt-fMRI-Neurofeebackwill receive feedback from the STG |
| sham-rt-fMRI | Sham comparator | Other: sham-rt-fMRI-Neurofeedbackwill receive feedback from the motor cortex |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- patients diagnosed with SZ or schizoaffective disorder using DSM-5 criteria
- auditory hallucinations not responsive to pharmacology as determined by chart review and a clinical interview of SCID.
Key exclusion criteria (6 listed)
- neurologic illness
- major head trauma
- electroconvulsive therapy
- alcohol or drug dependence
- alcohol or drug abuse within the past five years
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stg-rt-fMRI-Neurofeebackthe patients will receive real-time feedback from the brain activity of the superior temporal gyrus | Other | stg-rt-fMRI |
| sham-rt-fMRI-Neurofeedbackthe patients will receive real-time feedback from the brain activity of the somato-motor cortex | Other | sham-rt-fMRI |
Primary outcome
percent change in the STG BOLD signal, post- relative to pre-NFB
Time frame: 0-4 weeks post intervention
does real-time fMRI neurofidback reduce BOLD activity in STG, post NFB
2 secondary outcomes
reduction in scores on Psychotic Symptoms Rating Scale, post- relative to pre, NFB
Time frame: 0-4 weeks post intervention
percent change in the MPFC-PCC connectivity measure, post- relative to pre-NFB.
Time frame: 0-4 weeks post intervention
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2025.
- Individual participant dataSharing planned: Yes. The Clinical, Cognitive and Imaging data will be made publicly available
Related trials for Schizophrenia
RecruitingPhase 3
A Study to Evaluate the Long-term Safety and Tolerability of Xanomeline and Trospium Chloride for the Treatment of Psychiatric Disorders in Children and Adolescents
Schizophrenia, Autism-Related Irritability
Not yet recruiting
Deep Brain Stimulation for Treatment-Resistant Schizophrenia
Treatment Resistant Disorders
Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Active, not recruiting
Designing and Evaluating a Classroom-Based Mental Health Programme for Adolescents.
Mental Health Promotion
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
margaret niznikiewicz principal investigator
Boston VA Research Institute, Inc.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing stg-rt-fMRI-Neurofeeback in people with Schizophrenia and Auditory Hallucination, run by Boston VA Research Institute, Inc. at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 18 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact margaret niznikiewicz, PhD (6176534627, margaret_niznikiewicz@hms.harvard.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
percent change in the STG BOLD signal, post- relative to pre-NFB (time frame: 0-4 weeks post intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2025.