Treatment-resistant SchizophreniaNCT02361554
Deep Brain Stimulation in Treatment Resistant Schizophrenia
A study testing Medtronic Percept with SensSight Deep Brain Stimulation System in people with Treatment-resistant Schizophrenia, run by Johns Hopkins University at 1 site in United States.
Trial summary
The purpose of this pilot study is to investigate the use of deep brain stimulation (DBS) of the substantia nigra pars reticulata (SNr) in subjects with treatment-resistant schizophrenia. Read more about this study
- Who is it for?
- Ages 22 to 65 years
- Conditions the study is for
- Treatment-resistant Schizophrenia
- What is being tested?
- Medtronic Percept with SensSight Deep Brain Stimulation System
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Mar 2023to 28 Feb 2026
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 22 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Males and females who are at least 22 years of age.
- Subject has a diagnosis of schizophrenia or schizoaffective disorder as determined by a review of medical records, discussion with referring psychiatrist as well as the Structured Clinical Interview for DSM-V (SCID-V).
- Subject determined to be treatment-resistant for at least one year prior to the Screening Visit as demonstrated by clinical evidence (determined by review of medical records and discussion with referring psychiatrist) of persistent auditory hallucinations and/or delusions that have not responded to treatment with three adequate regimens of antipsychotic medication including one failed trial of clozapine as defined as follows:
- Adequate trials of two different antipsychotic drugs (not including clozapine) belonging to different classes of at least 12 weeks equivalent to at least 500 mg/day of chlorpromazine within the previous 5 years.
- A trial of clozapine of at least12 weeks at a dose of at least 400 mg (or a clozapine level of at least 350 ng/mL). Subjects who were unable to tolerate clozapine at this dose or for this duration because of intolerable side effects are also eligible.
- Subject has at least a score of 6 (severe) on 2 of the 4 BPRS positive symptoms (conceptual disorganization, grandiosity, hallucinatory behavior and unusual thought content) at all three Baseline Visits prior to undergoing surgery. One of the 2 must be hallucinatory behavior.
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- Subject must be ambulatory.
- Females who are postmenopausal, physically incapable of childbearing, or practicing an acceptable method of birth control. Acceptable methods of birth control include surgical sterilization, hormonal contraceptives, or double-barrier methods (condom or diaphragm with a spermicidal agent or intrauterine device [IUD]). If practicing an acceptable method of birth control, a negative urine pregnancy test result has been obtained at baseline Visits 1 and 3.
- Subject is determined by independent psychiatrist with expertise in capacity assessments to have decision-making capacity to provide informed consent.
- Subject is able to read English, understand and cooperate with study procedures, and has signed a written informed consent form prior to any study procedures.
Who cannot join
- Subject has a positive urine drug screen at any of the three Baseline Visits.
- Subject had major surgery within three months prior to Baseline Visit 1 or has other surgery planned during the proposed study period.
- Subject is determined by medical consultant to have medical contraindications to undergoing surgery.
- Subject is pregnant or breast-feeding.
- Subject has a history of alcohol or drug abuse within the past 6 months and dependence within the past year.
- Subject has a medical illness/condition, co-morbid psychiatric illness, and/or abnormal diagnostic finding that would interfere with the completion of the study, confound the results of the study, or pose risk to the patient.
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- Subject has participated in another investigational drug trial or therapeutic trial within 30 days of Baseline Visit 1.
- Subject has a diagnosis of mental retardation.
- Subject has a neurological condition, or a history of traumatic brain injury associated with loss of consciousness of > 1 hour and/or intracranial/epidural/subdural bleeding.
- Subject has defibrillator or pacemaker or other implants that will interfere with MRI and functioning of the device.
- Unstable psycho-social condition including housing and poor support.
Trial locations and contacts
1 site in 1 country.
United States1 site
The Johns Hopkins Hospital
Baltimore, Maryland, 21287
About this study
The purpose of this pilot study is to investigate the use of deep brain stimulation (DBS) of the substantia nigra pars reticulata (SNr) in subjects with treatment-resistant schizophrenia. There is a subset of patients with schizophrenia who continue to have persistent psychotic symptoms (auditory hallucinations and delusions) despite multiple adequate medication trials with antipsychotic medications including clozapine. There are currently no available treatments for such patients who generally have poor function and are chronically disabled, unable to work, live independently or have meaningful social relationships. Neuroimaging studies in patients with schizophrenia have revealed information about pathological neural circuits that could be suitable targets using deep brain stimulation. Although not yet tested in patients with schizophrenia, DBS is in early phase clinical trials in other psychiatric disorders.
This pilot study will investigate the use of DBS in treatment-resistant schizophrenia subjects who have exhausted all other therapeutic alternatives but continue to have persistent disabling psychotic symptoms. Of note, DBS is not FDA approved for use in patients with schizophrenia. The method will be similar to that used in subthalamic nucleus stimulation in patients with Parkinson's Disease. However, the electrode will be advanced slightly inferior into the SNr, a major outflow nucleus of the basal ganglia, with the intention of causing local inhibition of SNr outflow resulting in disinhibition of the mediodorsal nucleus (MDN) of the thalamus. Hypofunction of the MDN has been implicated in the pathophysiology of schizophrenia in post-mortem as well as multiple structural and functional imaging studies. Evidence suggests that dysfunction of the MD is implicated in both positive and cognitive symptoms (such as working memory impairment) in schizophrenia. Frequent monitoring and clinical assessment with psychiatric scales will be used to monitor treatment response.
- Conditions
- Treatment-resistant Schizophrenia
- Being tested
- Medtronic Percept with SensSight Deep Brain Stimulation System
- Medical subject headings
- Schizophrenia, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Medtronic Percept with SensSight Deep Brain Stimulation SystemDevice
Placement of Deep brain stimulation System for treatment of chronic auditory hallucinations in treatment-resistant schizophrenia
| Study group | Role | What they receive |
|---|---|---|
| Deep Brain Stimulation Implant | Experimental | Unblinded treatment arm, deep brain stimulation of the substantia nigra pars reticulata for treatment resistant schizophrenia. Receives: Device: Medtronic Percept with SensSight Deep Brain Stimulation System |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline in the Brief Psychiatric Rating Scale
We will assess deep brain stimulation effects on the positive and psychosis features of schizophrenia.
Measured: 1 year after neurostimulator implantation
Change from baseline in the Scales for the Assessment of Negative Symptoms (SANS)
We will assess deep brain stimulation effects on negative symptoms aspects of schizophrenia.
Measured: 1 year after neurostimulator implantation
Incidence of adverse device effects (ADEs).
We will assess the incidence of adverse device effects as defined by the Code of Federal Regulations (21 CFR 812.3)
Measured: 1 year after neurostimulator implantation
Secondary outcomes (2)
Change from baseline in the Young Mania scale (YMS)
We will assess deep brain stimulation effects on mania as assessed by the YMS.
Measured: 1 year after neurostimulator implantation
Change from baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive test battery.
We will assess deep brain stimulation effects on cognition as assessed by the MATRICS cognitive test battery.
Measured: 1 year after neurostimulator implantation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2015 (estimated)
- Study start1 Mar 2023
- Primary completion28 Feb 2026
- Study completion28 Feb 2026
Why it stopped: NIMH did not fund the 4th year of the UOI grant
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment-resistant SchizophreniaStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Sponsor
- Investigators
- Nicola Cascella, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02361554
- Sponsor's protocol ID
- NA_00042065
- Status last verified
- May 2026
- First submitted
- 6 Feb 2015
- Last updated
- 14 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 14 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Deep Brain Stimulation in Treatment Resistant Schizophrenia
- ClinicalTrials.gov ID
- NCT02361554
- Acronym / sponsor ID
- NA_00042065
- Conditions
- Treatment-resistant Schizophrenia
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: NIMH did not fund the 4th year of the UOI grant
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Johns Hopkins UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Mar 2023 (actual)
- Primary completion
- 28 Feb 2026 (actual)
- Study completion
- 28 Feb 2026 (actual)
- First posted
- 11 Feb 2015 (estimated)
- 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.
The purpose of this pilot study is to investigate the use of deep brain stimulation (DBS) of the substantia nigra pars reticulata (SNr) in subjects with treatment-resistant schizophrenia. There is a subset of patients with schizophrenia who continue to have persistent psychotic symptoms (auditory hallucinations and delusions) despite multiple adequate medication trials with antipsychotic medications including clozapine. There are currently no available treatments for such patients who generally have poor function and are chronically disabled, unable to work, live independently or have meaningful social relationships. Neuroimaging studies in patients with schizophrenia have revealed information about pathological neural circuits that could be suitable targets using deep brain stimulation. Although not yet tested in patients with schizophrenia, DBS is in early phase clinical trials in other psychiatric disorders.
This pilot study will investigate the use of DBS in treatment-resistant schizophrenia subjects who have exhausted all other therapeutic alternatives but continue to have persistent disabling psychotic symptoms. Of note, DBS is not FDA approved for use in patients with schizophrenia. The method will be similar to that used in subthalamic nucleus stimulation in patients with Parkinson's Disease. However, the electrode will be advanced slightly inferior into the SNr, a major outflow nucleus of the basal ganglia, with the intention of causing local inhibition of SNr outflow resulting in disinhibition of the mediodorsal nucleus (MDN) of the thalamus. Hypofunction of the MDN has been implicated in the pathophysiology of schizophrenia in post-mortem as well as multiple structural and functional imaging studies. Evidence suggests that dysfunction of the MD is implicated in both positive and cognitive symptoms (such as working memory impairment) in schizophrenia. Frequent monitoring and clinical assessment with psychiatric scales will be used to monitor treatment response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Deep Brain Stimulation Implant | Experimental | Device: Medtronic Percept with SensSight Deep Brain Stimulation SystemUnblinded treatment arm, deep brain stimulation of the substantia nigra pars reticulata for treatment resistant schizophrenia. |
Who may qualify
- Ages
- 22 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Males and females who are at least 22 years of age.
- Subject has a diagnosis of schizophrenia or schizoaffective disorder as determined by a review of medical records, discussion with referring psychiatrist as well as the Structured Clinical Interview for DSM-V (SCID-V).
- Subject determined to be treatment-resistant for at least one year prior to the Screening Visit as demonstrated by clinical evidence (determined by review of medical records and discussion with referring psychiatrist) of persistent auditory hallucinations and/or delusions that have not responded to treatment with three adequate regimens of antipsychotic medication including one failed trial of clozapine as defined as follows:
- Subject has at least a score of 6 (severe) on 2 of the 4 BPRS positive symptoms (conceptual disorganization, grandiosity, hallucinatory behavior and unusual thought content) at all three Baseline Visits prior to undergoing surgery. One of the 2 must be hallucinatory behavior.
- Subject must be ambulatory.
Key exclusion criteria (11 listed)
- Subject has a positive urine drug screen at any of the three Baseline Visits.
- Subject had major surgery within three months prior to Baseline Visit 1 or has other surgery planned during the proposed study period.
- Subject is determined by medical consultant to have medical contraindications to undergoing surgery.
- Subject is pregnant or breast-feeding.
- Subject has a history of alcohol or drug abuse within the past 6 months and dependence within the past year.
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 |
|---|---|---|
| Medtronic Percept with SensSight Deep Brain Stimulation SystemPlacement of Deep brain stimulation System for treatment of chronic auditory hallucinations in treatment-resistant schizophrenia | Device | Deep Brain Stimulation Implant |
Primary outcome
Change from baseline in the Brief Psychiatric Rating Scale
Time frame: 1 year after neurostimulator implantation
We will assess deep brain stimulation effects on the positive and psychosis features of schizophrenia.
Change from baseline in the Scales for the Assessment of Negative Symptoms (SANS)
Time frame: 1 year after neurostimulator implantation
We will assess deep brain stimulation effects on negative symptoms aspects of schizophrenia.
Incidence of adverse device effects (ADEs).
Time frame: 1 year after neurostimulator implantation
We will assess the incidence of adverse device effects as defined by the Code of Federal Regulations (21 CFR 812.3)
2 secondary outcomes
Change from baseline in the Young Mania scale (YMS)
Time frame: 1 year after neurostimulator implantation
Change from baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive test battery.
Time frame: 1 year after neurostimulator implantation
Results and safety
The study was stopped early (reason given: NIMH did not fund the 4th year of the UOI grant). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 May 2026.
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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. This study is not recruiting at the moment.
Nicola Cascella principal investigator
Johns Hopkins University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Medtronic Percept with SensSight Deep Brain Stimulation System in people with Treatment-resistant Schizophrenia, run by Johns Hopkins University 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 10 inclusion and 11 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: stopped early, as of the sponsor's last update on 14 May 2026. 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. 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?
The study was stopped early (reason given: NIMH did not fund the 4th year of the UOI grant). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline in the Brief Psychiatric Rating Scale (time frame: 1 year after neurostimulator implantation). The study lists 3 primary outcomes in all. 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 14 May 2026.