Deep Brain Stimulation for Psychosis

NCT06257056 | Recruiting DMC FDA Device

• 1 other identifier: STU-2023-0110
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief 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. 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:

1. 1.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.
2. 2.Develop closed loop stimulation protocols to modify brain states during psychotic brain activity induced by low-dose ketamine administration.
3. 3.Investigate the use of mnemonic similarity to characterize brain networks related to symptoms of treatment-refractory schizophrenia.
4. 4.Treatment-related objectives: Record a reduction in psychotic symptoms, as well as an improvement in psychosocial function and cognition.

Conditions

Treatment-Refractory Schizophrenia

Keywords

Deep Brain Stimulation; Schizophrenia; Treatment Resistant Schizophrenia

Outcome Measures

Primary Outcomes (1)

• 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.

  3 years

Study Arms (2)

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.

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.

Device: Abbott Laboratories Infinity™ implantable deep brain stimulation system

Interventions

Abbott Laboratories Infinity™ implantable deep brain stimulation system DEVICE

Deep brain stimulation (DBS) refers to the process of delivering an electrical current to a precise location in the brain

Experimental: Randomized Discontinuation Period: ON then OFF DBS; Randomized Discontinuation Period: OFF then ON DBS

Eligibility Criteria

• Age: 22 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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;
• 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.
• For women of childbearing potential:

You may not qualify if:

• 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;
• 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.

Sponsors & Collaborators

• Bradley Lega: lead

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

RECRUITING

MeSH Terms

Conditions

Schizophrenia; Schizophrenia, Treatment-Resistant

Condition Hierarchy (Ancestors)

Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders

Study Officials

• Bradley Lega, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• David McDonagh, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Nader Pouratian, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

• Carol Tamminga, M.D.

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Hila Abush Segev, Ph.D

CONTACT

214-648-0401; Hila.AbushSegev@UTSouthwestern.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: The investigators propose a clinical trial involving 12-months open-label bilateral DBS in subjects with treatment refractory schizophrenia. The open label period is intended to ensure that maximal benefit can be achieved with the current proposed protocol. Following open label optimization, to control for possible placebo, each subject will enter a double blinded randomized discontinuation, intended to confirm clinical benefit of DBS among responders (4 months).
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Model Details: 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.

Study Record Dates

• First Submitted: February 5, 2024
• First Posted: February 13, 2024
• Study Start: April 3, 2024
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: May 30, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)