Treatment-Refractory SchizophreniaNCT06257056
Deep Brain Stimulation for Psychosis
A study testing Abbott Laboratories Infinity™ implantable deep brain stimulation system in people with Treatment-Refractory Schizophrenia, run by Bradley Lega at 1 site in United States.
Trial summary
There are three hypotheses proposed for this study: 1) Participants will report no unanticipated serious adverse events during the eight months of treatment. 2) Investigators will successfully model psychotic versus non-psychotic brain states using support vector machine (SVM) classifiers. Read more about this study
- Who is it for?
- Ages 22 to 70 years
- Conditions the study is for
- Treatment-Refractory Schizophrenia
- What is being tested?
- Abbott Laboratories Infinity™ implantable deep brain stimulation system
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteUnited States
- Study dates
- 3 Apr 2024to Apr 2027
- 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 22 to 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women (non-pregnant) between ages 22 and 70;
- Diagnostic and Statistical Manual of Mental Disorders (DSM) -5 diagnosis (assessed by Structured Clinical Interview for DSM-5 Axis I disorders SCID-5) of schizophrenia as the primary diagnosis.
- Medically healthy, without any acute serious medical disorders
- Treatment refractory and previous trials of treatment defined as: Demonstrated non-sustained response to at least two different antipsychotic drugs from two different chemical families. And demonstrated non-sustained response to at least either an electroconvulsive therapy (ECT) or a clozapine trial.
- Suffering from active and ongoing psychotic symptoms of a continuous and aversive nature.
- The PANSS must remain greater than or equal to 90 on two separate assessments (at initial screening and 1 week before surgery), over a 1-month period;
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- At least one item on the PANSS positive subscale is 5 or greater.
- Normal brain MRI within 3 months of surgery;
- Stable antipsychotic medication regimen for the month preceding surgery;
- Normal thyroid stimulating hormone (TSH) level within 12 months of study entry;
- Other medical conditions must be stable for at least 6 months;
- Able and willing to give informed consent and agree to attend regular clinic visits for at least 12 months following surgery;
- Able to have a treating psychiatrist or close relative present for discussions about the study and co-sign informed consent;
- Willingness to sign Treatment Contract.
- Participants with a family or caregiver support system to aid the participant throughout the study will be preferentially selected for inclusion.
- For women of childbearing potential:
- Required to provide a negative pregnancy blood test during screening phase of the study, and during several additional timepoints throughout study participation.
- Obligated to use highly effective (those that when used alone or in combination, result in a low failure rate [i.e., less than 1 percent per year], when used consistently and correctly) methods of birth control throughout study participation.
- Will be allowed to participate in the study only after a confirmed menstrual period.
- For men: Obligated to use highly effective (those that when used alone or in combination, result in a low failure rate [i.e., less than 1 percent per year], when used consistently and correctly) methods of birth control throughout study participation.
Who cannot join
- Active alcohol or substance use disorder within 6 months, excluding nicotine; Urine drug test positive for illicit drugs;
- Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or made a suicide attempt within the last year; or as identified as The Columbia Suicide Severity Rating Scale (C-SSRS),
- Neurological/Medical condition that makes the participant, in the opinion of the surgeon, a poor surgical candidate (e.g., progressive neurodegenerative disorder, significant cardiopulmonary disorder, need for chronic anticoagulation);
- Any history of seizure disorder, hemorrhagic stroke, or has high risk of seizure (history of congenital brain malformation, history of brain injury, neuro-developmental disorder, currently taking medication that is known to lower seizure threshold, or other factors that predispose seizures);
- Any medical contraindication to surgery such as infection;
- Coagulopathy: Bleeding propensity and/or one of the following: international normalised ratio (INR) > 1.5; prolonged activated partial thromboplastin time (aPTT) ≥ 45 sec; platelet count < 100×103 /uL;
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- Uncontrolled hypertension (systolic > 140mmHg and/or diastolic > 90 mmHg), demonstrated on each of three repeated measurements taken within one hour regardless of whether or not the participant is taking antihypertensive medications.
- Patients with a heart-rate corrected QT interval (QTc) of > 450 msec
- Participation in another drug, device, or biological study within 90 days;
- Current implanted stimulation devices including cardiac pacemakers, defibrillators, and neurostimulators including spinal cord stimulators and deep brain stimulators;
- Need for Diathermy;
- Chronic use of anticoagulant or anti-platelet agents that cannot be safely stopped for a sufficient duration (minimum 2.5 weeks) in the peri-operative period.
- Any Psychiatric/Neurological/Medical condition that makes the participant, in the opinion of the Investigator, a poor candidate.
- A female participant of childbearing potential who is not able or willing to use highly effective (those that when used alone or in combination, result in a low failure rate [i.e., less than 1 percent per year], when used consistently and correctly) methods of birth control throughout the duration of participation in the trial.
- A female participant of childbearing potential who is not able or willing to provide a negative pregnancy blood test during the screening phase of the study and during several additional timepoints throughout study participation. Specifically, the investigators will require a pregnancy test on the day of ketamine (or placebo) administration to avoid the risk of administering ketamine to a pregnant patient.
- A separate cardiac condition that, in the opinion of study physician would present an unacceptable risk of undergoing general anesthesia or ketamine administration.
- Participants with poorly controlled hypertension or persistent tachycardia, at baseline, will be excluded.
- Participants who are taking an anti-depressant medication.
- Any known contraindications for ketamine and/or esketamine (Spravato):
- Patients for whom a significant elevation of blood pressure would constitute a serious hazard, according to the opinion of the study PI.
- Patients with known hypersensitivity to ketamine, esketamine, or to any of the excipients.
- Patients with Aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial, and peripheral arterial vessels) or arteriovenous malformation.
- Patients with a history of intracerebral hemorrhage.
- Patients with resting heart rate over 90 or below 55 beats per minute (BPM)
- Participants taking a medication with a known interaction with ketamine or esketamine (amphetamines, monoamine oxidase (MAO)-Is, aminophylline, theophylline, norepinephrine, epinephrine, vasopressin, dobutamine, ephedrine, ethanol, Ergometrine/Ergonovine). Patients taking benzodiazepines will not be excluded as this is recommended to prompt monitoring of patients in the information for esketamine. Dr. McDonagh will review such cases including for symptoms of sedation associated with their use and the dosage and duration of therapy for each. The investigators will exclude subjects who have any evidence of central nervous system (CNS) depression, such as decreased level of arousal or respiratory depression, thought to be linked with CNS depressants. The investigators will use the PRODIGY score to exclude any patient taking one of these medicines determined to be HIGH risk (score of 15 points or higher, https://www.apsf.org/wp-content/uploads/newsletters/online-only/202006/PRODIGY-Interactive-Risk-Assessment-Tool.pdf). The investigators note that ketamine has been used as an adjunct for sedation with benzodiazepines and opiates in the anesthesia environment, and the FDA's guidance on ketamine states: "KETALAR has been studied in over 12,000 operative and diagnostic procedures, involving over 10,000 patients from 105 separate studies. During the course of these studies KETALAR was administered as the sole agent, as induction for other general agents, or to supplement low-potency agents."
- During the ketamine administration phase in the hospital, patients with a history of benzodiazepine (or other CNS depressant) usage will undergo more frequent documentation of respiratory rate and heart rate (every 10 minutes). All patients will undergo continuous pulse oximetry monitoring to initiate supportive measures if there is any evidence of respiratory depression. In any patient with a history of opiate or 3-quinuclidinyl benzilate (BZ) administration, the investigators will have both flumazenil and naloxone immediately available at the bedside for administration if there is any evidence of respiratory distress.
- On the day of planned ketamine (or placebo) administration, Dr. McDonagh will review all medicines being administered to the patient to ensure there is no potential interaction. This will be documented on the Ketamine Administration Checklist included in appendix 6.
- On the day of planned ketamine (or placebo) administration, subjects will undergo a urine drug screen to avoid the accidental administration of ketamine to a patient who tests positive for any agents that is contraindicated (such as psychostimulants or CNS depressants). This is now reflected in the ketamine administration checklist (appendix 6).
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
UT Southwestern Medical Center
Dallas, Texas, 75390
Hila Abush Segev, Ph.D, 214-648-0401, Hila.AbushSegev@UTSouthwestern.edu
About this study
Official title: Closed Loop Neuromodulation for Treatment-refractory Schizophrenia: A Pilot Study
There are three hypotheses proposed for this study: 1) Participants will report no unanticipated serious adverse events during the eight months of treatment. 2) Investigators will successfully model psychotic versus non-psychotic brain states using support vector machine (SVM) classifiers. 3) Participants specific brain stimulation parameters can induce a change in the brain state consistent with non-psychotic states as measured by classifier output. Hypotheses 1, 2, and 3 address safety and tolerability, efficacy, and the putative mechanism of successful treatment.
The overall objective is to use next generation Deep Brain Stimulation (DBS) combined with antecedent stereo electroencephalogram (SEEG) mapping to establish a new therapy for treatment-refractory schizophrenia given the limitations of current treatment modalities.
Read more
The primary objective is to demonstrate safety of acute and chronic network guided stimulation for treatment-refractory schizophrenia.
Exploratory Objectives:
- Use intracranial mapping (SEEG) combined with pharmacological manipulation of psychotic states to create a protocol for participant specific deep brain stimulation to treat treatment-refractory schizophrenia.
- Develop closed loop stimulation protocols to modify brain states during psychotic brain activity induced by low-dose ketamine administration.
- Investigate the use of mnemonic similarity to characterize brain networks related to symptoms of treatment-refractory schizophrenia.
- Treatment-related objectives: Record a reduction in psychotic symptoms, as well as an improvement in psychosocial function and cognition.
- Conditions
- Treatment-Refractory Schizophrenia
- Being tested
- Abbott Laboratories Infinity™ implantable deep brain stimulation system
- Keywords
- Deep Brain Stimulation, Schizophrenia, Treatment Resistant Schizophrenia
- Medical subject headings
- Schizophrenia, Schizophrenia, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Abbott Laboratories Infinity™ implantable deep brain stimulation systemDevice
Deep brain stimulation (DBS) refers to the process of delivering an electrical current to a precise location in the brain
| Study group | Role | What they receive |
|---|---|---|
| Randomized Discontinuation Period: OFF then ON DBS | Experimental | Subjects randomized to this arm are initially "OFF" DBS after the open label period then gradually decreased in their optimized setting's amplitude for 8 weeks and then "ON" DBS for 8 weeks. Receives: Device: Abbott Laboratories Infinity™ implantable deep brain stimulation system |
| Experimental: Randomized Discontinuation Period: ON then OFF DBS | Experimental | Subjects randomized to this arm are initially "ON" DBS with optimized stimulation settings for 8 weeks after the open label period and then "OFF" DBS with gradually decreasing amplitude for 8 weeks. Receives: Device: Abbott Laboratories Infinity™ implantable deep brain stimulation system |
What is being measured
The primary outcome is the main question the study is designed to answer.
Demonstrate device safety
The primary objective is to demonstrate safety of acute and chronic network guided stimulation for treatment-refractory schizophrenia. This is determined if participants with the Deep Brain Stimulation Device demonstrate no significant device related serious adverse events (SAE).
Device safety will be measured by number of reported SAE's in year 2 and 3.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Feb 2024
- Study start3 Apr 2024
- Primary completionApr 2027 (estimated)
- Study completionApr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Treatment-Refractory 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
- Sequential
- Model description
- Participants will undergo a maximum of two experimental sessions with ketamine and at least one with placebo. No participant will undergo more than two ketamine administration sessions. This is an overall 12-month feasibility and safety study. The first 8-months will be open-label bilateral DBS that targets a brain region within brain networks implicated in schizophrenia, which will be followed by a 4-month double-blind randomized discontinuation study. After 8 months, participants will enter a double blind (participant and rater) discontinuation study for 4-months to confirm the clinical benefit of DBS among responders. Final Go-No Go checkpoint occurs after final participants reaches the end of the 12-month study period. Participants will be randomized to either the ON or OFF stimulation phase for 2 months each. If randomization is initially in the ON phase, for the first 2 months, there will be no change in the stimulation settings.
- Masking
- None (open label)
- Enrolment
- 10 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bradley Lega
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bradley Lega, University of Texas Southwestern Medical Center
- Investigators
- Bradley Lega, M.D., Principal investigator, University of Texas Southwestern Medical CenterDavid McDonagh, M.D., Principal investigator, University of Texas Southwestern Medical CenterNader Pouratian, M.D., Principal investigator, University of Texas Southwestern Medical CenterCarol Tamminga, M.D., Principal investigator, University of Texas Southwestern Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06257056
- Sponsor's protocol ID
- STU-2023-0110
- Status last verified
- Jun 2026
- First submitted
- 5 Feb 2024
- Last updated
- 9 Jun 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No: Investigators with established research programs will be eligible for data sharing. Interested investigators will be required to submit a summary of proposed work and requested data elements. If approved by the Principal Investigator of the study, data will be shared. This data will be de-identified and coded. There is no plan to share identifiers outside the study team
Study at a glance
From the registry record, last updated by the sponsor on 9 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Closed Loop Neuromodulation for Treatment-refractory Schizophrenia: A Pilot Study
- ClinicalTrials.gov ID
- NCT06257056
- Acronym / sponsor ID
- STU-2023-0110
- Conditions
- Treatment-Refractory Schizophrenia
- Keywords
- Deep Brain Stimulation, Schizophrenia, Treatment Resistant Schizophrenia
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 10 participants (estimated)
- Lead sponsor
- Bradley LegaUniversity, hospital or other
- Study start
- 3 Apr 2024 (actual)
- Primary completion
- Apr 2027 (estimated)
- Study completion
- Apr 2027 (estimated)
- First posted
- 13 Feb 2024 (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.
There are three hypotheses proposed for this study: 1) Participants will report no unanticipated serious adverse events during the eight months of treatment. 2) Investigators will successfully model psychotic versus non-psychotic brain states using support vector machine (SVM) classifiers. 3) Participants specific brain stimulation parameters can induce a change in the brain state consistent with non-psychotic states as measured by classifier output. Hypotheses 1, 2, and 3 address safety and tolerability, efficacy, and the putative mechanism of successful treatment.
The overall objective is to use next generation Deep Brain Stimulation (DBS) combined with antecedent stereo electroencephalogram (SEEG) mapping to establish a new therapy for treatment-refractory schizophrenia given the limitations of current treatment modalities.
The primary objective is to demonstrate safety of acute and chronic network guided stimulation for treatment-refractory schizophrenia.
Exploratory Objectives:
- Use intracranial mapping (SEEG) combined with pharmacological manipulation of psychotic states to create a protocol for participant specific deep brain stimulation to treat treatment-refractory schizophrenia.
- Develop closed loop stimulation protocols to modify brain states during psychotic brain activity induced by low-dose ketamine administration.
- Investigate the use of mnemonic similarity to characterize brain networks related to symptoms of treatment-refractory schizophrenia.
- Treatment-related objectives: Record a reduction in psychotic symptoms, as well as an improvement in psychosocial function and cognition.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Participants will undergo a maximum of two experimental sessions with ketamine and at least one with placebo. No participant will undergo more than two ketamine administration sessions. This is an overall 12-month feasibility and safety study. The first 8-months will be open-label bilateral DBS that targets a brain region within brain networks implicated in schizophrenia, which will be followed by a 4-month double-blind randomized discontinuation study. After 8 months, participants will enter a double blind (participant and rater) discontinuation study for 4-months to confirm the clinical benefit of DBS among responders. Final Go-No Go checkpoint occurs after final participants reaches the end of the 12-month study period. Participants will be randomized to either the ON or OFF stimulation phase for 2 months each. If randomization is initially in the ON phase, for the first 2 months, there will be no change in the stimulation settings.
| Arm | Type | Receives |
|---|---|---|
| Randomized Discontinuation Period: OFF then ON DBS | Experimental | Device: Abbott Laboratories Infinity™ implantable deep brain stimulation systemSubjects randomized to this arm are initially "OFF" DBS after the open label period then gradually decreased in their optimized setting's amplitude for 8 weeks and then "ON" DBS for 8 weeks. |
| Experimental: Randomized Discontinuation Period: ON then OFF DBS | Experimental | Device: Abbott Laboratories Infinity™ implantable deep brain stimulation systemSubjects randomized to this arm are initially "ON" DBS with optimized stimulation settings for 8 weeks after the open label period and then "OFF" DBS with gradually decreasing amplitude for 8 weeks. |
Who may qualify
- Ages
- 22 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- Men and women (non-pregnant) between ages 22 and 70;
- Diagnostic and Statistical Manual of Mental Disorders (DSM) -5 diagnosis (assessed by Structured Clinical Interview for DSM-5 Axis I disorders SCID-5) of schizophrenia as the primary diagnosis.
- Medically healthy, without any acute serious medical disorders
- Treatment refractory and previous trials of treatment defined as: Demonstrated non-sustained response to at least two different antipsychotic drugs from two different chemical families. And demonstrated non-sustained response to at least either an electroconvulsive therapy (ECT) or a clozapine trial.
- Suffering from active and ongoing psychotic symptoms of a continuous and aversive nature.
Key exclusion criteria (28 listed)
- Active alcohol or substance use disorder within 6 months, excluding nicotine; Urine drug test positive for illicit drugs;
- Current substantial suicidal risk as defined by a plan or clear immediate intent for self-harm, or made a suicide attempt within the last year; or as identified as The Columbia Suicide Severity Rating Scale (C-SSRS),
- Neurological/Medical condition that makes the participant, in the opinion of the surgeon, a poor surgical candidate (e.g., progressive neurodegenerative disorder, significant cardiopulmonary disorder, need for chronic anticoagulation);
- Any history of seizure disorder, hemorrhagic stroke, or has high risk of seizure (history of congenital brain malformation, history of brain injury, neuro-developmental disorder, currently taking medication that is known to lower seizure threshold, or other factors that predispose seizures);
- Any medical contraindication to surgery such as infection;
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 |
|---|---|---|
| Abbott Laboratories Infinity™ implantable deep brain stimulation systemDeep brain stimulation (DBS) refers to the process of delivering an electrical current to a precise location in the brain | Device | Experimental: Randomized Discontinuation Period: ON then OFF DBS, Randomized Discontinuation Period: OFF then ON DBS |
Primary outcome
Demonstrate device safety
Time frame: 3 years
The primary objective is to demonstrate safety of acute and chronic network guided stimulation for treatment-refractory schizophrenia. This is determined if participants with the Deep Brain Stimulation Device demonstrate no significant device related serious adverse events (SAE). Device safety will be measured by number of reported SAE's in year 2 and 3.
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 9 Jun 2026.
- Individual participant dataSharing planned: No. Investigators with established research programs will be eligible for data sharing. Interested investigators will be required to submit a summary of proposed work and requested data elements. If approved by the Principal Investigator of the study, data will be shared. This data will be de-identified and coded. There is no plan to share identifiers outside the study team
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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.
Bradley Lega, M.D. principal investigator
University of Texas Southwestern Medical Center
David McDonagh, M.D. principal investigator
University of Texas Southwestern Medical Center
Nader Pouratian, M.D. principal investigator
University of Texas Southwestern Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Abbott Laboratories Infinity™ implantable deep brain stimulation system in people with Treatment-Refractory Schizophrenia, run by Bradley Lega 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 20 inclusion and 28 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 9 Jun 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?
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 Hila Abush Segev, Ph.D (214-648-0401, Hila.AbushSegev@UTSouthwestern.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Demonstrate device safety (time frame: 3 years). 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 9 Jun 2026.