Deep Brain Stimulation for Treatment-Resistant Schizophrenia

ConditionTreatment Resistant Disorders

Trial statusNot yet recruiting

Trial phaseNot applicable

Trial typeInterventional

Biological sexAll

Age22-65

SponsorJohns Hopkins University

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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).

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.

Disqualifiers

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.

Trial design

Design model

Single group

Treatments tested in this trial

Medtronic Percept with SensSight Deep Brain Stimulation System
Device
Placement of Deep brain stimulation System for treatment of chronic auditory hallucinations in treatment-resistant schizophrenia

Treatment groups

15 Participants

are divided into 1 treatment group

Group A: Deep Brain Stimulation ImplantExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

Change from baseline in the Brief Psychiatric Rating Scale

Investigators will assess deep brain stimulation effects on the positive and psychosis features of schizophrenia. Total scores range from 18 to 126. A higher score indicates a more severe psychiatric symptom rating.

Time frame