RECRUITING

Deep Brain Stimulation in Treatment Resistant Schizophrenia

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

Deep Brain Stimulation in Treatment Resistant Schizophrenia

Quick Facts

Study Start:2023-03-01

Study Completion:2027-06

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT02361554

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:22 Years to 65 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* 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: 1. 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. 2. 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. * 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.	* 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. * 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.

Inclusion Criteria

Exclusion Criteria

* 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:
1. 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.
2. 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.
* 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.

* 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.
* 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.

Contacts and Locations

Principal Investigator

Nicola Cascella

PRINCIPAL_INVESTIGATOR

Johns Hopkins University

Study Locations (Sites)

The Johns Hopkins Hospital

Baltimore, Maryland, 21287

United States

Collaborators and Investigators

Sponsor: Johns Hopkins University

Nicola Cascella, PRINCIPAL_INVESTIGATOR, Johns Hopkins University

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2023-03-01

Study Completion Date2027-06

Study Record Updates

Study Start Date2023-03-01

Study Completion Date2027-06

Terms related to this study

Additional Relevant MeSH Terms

Treatment-resistant Schizophrenia