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Deep Brain Stimulation in Treatment Resistant Schizophrenia

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ClinicalTrials.gov Identifier: NCT02361554
Recruitment Status : Recruiting
First Posted : February 11, 2015
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Johns Hopkins University

Tracking Information
First Submitted Date  ICMJE February 6, 2015
First Posted Date  ICMJE February 11, 2015
Last Update Posted Date March 25, 2019
Study Start Date  ICMJE June 2012
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 6, 2015)
  • Change from baseline in the Scales for the Assessment of Negative Symptoms (SANS) [ Time Frame: 1 year after neurostimulator implantation ]
    We will assess deep brain stimulation effects on negative symptoms aspects of schizophrenia.
  • Change from baseline in the Brief Psychiatric Rating Scale [ Time Frame: 1 year after neurostimulator implantation ]
    We will assess deep brain stimulation effects on the positive and psychosis features of schizophrenia.
  • Incidence of adverse device effects (ADEs). [ Time Frame: 1 year after neurostimulator implantation ]
    We will assess the incidence of adverse device effects as defined by the Code of Federal Regulations (21 CFR 812.3)
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT02361554 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: February 6, 2015)
  • Change from baseline in the Young Mania scale (YMS) [ Time Frame: 1 year after neurostimulator implantation ]
    We will assess deep brain stimulation effects on mania as assessed by the YMS.
  • Change from baseline in the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) cognitive test battery. [ Time Frame: 1 year after neurostimulator implantation ]
    We will assess deep brain stimulation effects on cognition as assessed by the MATRICS cognitive test battery.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Deep Brain Stimulation in Treatment Resistant Schizophrenia
Official Title  ICMJE Deep Brain Stimulation in Treatment Resistant Schizophrenia
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Treatment-resistant Schizophrenia
Intervention  ICMJE Device: Medtronic Activa Deep Brain Stimulation System
Study Arms  ICMJE Experimental: Deep Brain Stimulation Implant
Unblinded treatment arm, deep brain stimulation of the substantia nigra pars reticulata for treatment resistant schizophrenia.
Intervention: Device: Medtronic Activa Deep Brain Stimulation System
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 6, 2015)
3
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2020
Estimated Primary Completion Date June 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Males and females who are at least 22 years of age.
  • Subject has a diagnosis of schizophrenia as determined by a review of medical records, discussion with referring psychiatrist as well as the Structured Clinical Interview for DSM-IV (SCID-IV).
  • 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 3 BPRS positive symptoms (conceptual disorganization, hallucinatory behavior and unusual thought content) at all three Baseline Visits prior to undergoing surgery.
  • 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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 22 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02361554
Other Study ID Numbers  ICMJE NA_00042065
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Johns Hopkins University
Study Sponsor  ICMJE Johns Hopkins University
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Johns Hopkins University
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP