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Deep Brain Stimulation for Treatment-Resistant Schizophrenia

Deep Brain Stimulation in Treatment Resistant Schizophrenia

Who can join

As published by the study on ClinicalTrials.gov. "Not stated" means the study hasn't said — ask the study team.

Age
22 Years to 65 Years
Sex
All sexes
Healthy volunteers
Not accepted
Compensation
Not stated

Other requirements are listed under Eligibility below. Only the study team can confirm whether you can join.

What to expect

No one can promise a trial will help you personally — that is what the research is trying to find out.

What participation involves

Not stated in the study description — ask the study team about visits and procedures.

Compensation
Not stated
  • Study-related exams and procedures are typically provided at no cost. This is how many trials work in general — confirm the details for this study with the study team.
  • Participants are monitored closely by the research team throughout the study.
  • Some participants may receive access to an investigational treatment, which is still being studied.
  • Your participation helps researchers learn whether this approach could help future patients.

About this study

In plain language

This small study tests deep brain stimulation (DBS), which uses an implanted device to send electrical signals to a brain area called the SNr. It is for adults with schizophrenia or schizoaffective disorder whose severe symptoms have not improved with several medicines, including clozapine. DBS is not FDA-approved to treat schizophrenia.

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.

Compensation is read from the study's own description and may be missing — always confirm with the study team.

Eligibility

Who can join

  • Be at least 22 years old and have schizophrenia or schizoaffective disorder confirmed by the study team.
  • For at least 1 year, have heard voices or held false beliefs that did not improve with 3 antipsychotic medicines. These medicines treat symptoms of psychosis.
  • Have tried 2 different types of antipsychotic medicines in the past 5 years, each for at least 12 weeks at the required dose.
  • Have tried clozapine for at least 12 weeks at the required dose or blood level. You may also qualify if side effects kept you from taking enough clozapine or taking it long enough.
  • Have severe symptoms on the study rating scale at all 3 visits before surgery. At least 2 symptoms must be severe, including hearing or seeing things that are not there.
  • Be able to walk.
  • If female, be past menopause, unable to become pregnant, or using an accepted birth control method. Those using birth control must have negative pregnancy tests at 2 required visits.
  • Be able to read English, understand and follow study steps, and sign a consent form. An independent psychiatrist must confirm that you can decide whether to join.

Who can't join

  • Have a positive urine drug test at any of the 3 visits before surgery, alcohol or drug abuse in the past 6 months, or dependence in the past year.
  • Had major surgery in the past 3 months, plan other surgery during the study, or have a medical reason that makes surgery unsafe.
  • Are pregnant or breastfeeding.
  • Have another medical or mental health condition, or an unusual test result, that could make the study unsafe or affect its results or completion.
  • Joined another study testing a drug or treatment within 30 days before the first baseline visit, or have an intellectual disability.
  • Have a nervous system condition, or a past brain injury with loss of consciousness for more than 1 hour or bleeding in or around the brain.
  • Have a pacemaker, defibrillator, or another implant that would interfere with MRI scans or the DBS device.
  • Have an unstable living or social situation, including unstable housing or poor support.

Simplified for readability. The official criteria below are what the study team uses.

Official eligibility criteria

Inclusion 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 Brief Psychiatric Rating Scale (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. Exclusion Criteria: * 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.

Study sites (1)

MD