<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03829124</url>
  </required_header>
  <id_info>
    <org_study_id>201800056A3</org_study_id>
    <nct_id>NCT03829124</nct_id>
  </id_info>
  <brief_title>Comparison of Ketamine Combine Propofol vs Propofol Anesthesia in Schizophrenia Electroconvulsive Therapy</brief_title>
  <official_title>Comparison of Propofol Combine Ketamine Anesthesia and Propofol Anesthesia in Schizophrenia Electroconvulsive Therapy: A Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Electroconvulsive therapy (ECT) serves as an effective adjuvant modality for major depressive&#xD;
      disorder, schizophrenia, or bipolar affective disorder refractory to or contraindicated to&#xD;
      psychopharmacological treatment. Anesthetics have been introduced into ECT sessions to&#xD;
      alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia, hypertension, and&#xD;
      anxiety.&#xD;
&#xD;
      Propofol is able to rapidly cross the blood-brain barrier (BBB), which leads to rapid onset&#xD;
      of sedation and hypnosis. Meanwhile, propofol has hemodynamic depressant effect and&#xD;
      attenuates hypertensive surge during ECT. Characteristics mentioned above make propofol one&#xD;
      of widely used anesthetics for anesthetized ECT. However, propofol is also well known for&#xD;
      anticonvulsant property. Thus, dosage of electrical stimulus may be increased to achieve&#xD;
      ideal seizure quality in this setting, which also leads to higher risk of subsequent&#xD;
      cognitive impairment or other complications.&#xD;
&#xD;
      Ketamine has also been widely used in the induction of anesthesia for the treatment of major&#xD;
      depressive disease in recent years. It has been found to increase the permeability and&#xD;
      therapeutic effect of antidepressants. Compared to traditional Barbiturate drugs or propofol,&#xD;
      do not increase the threshold of electricity required by electroporation, which can reduce&#xD;
      the time required for symptom relief of those drugs, It is a viable alternative induction&#xD;
      drug.&#xD;
&#xD;
      There have been confirmed that ketamine combine propofol can be used for electroconvulsive&#xD;
      treatment in patients with major depression and bipolar disorder, and even better&#xD;
      Electroconvulsive quality can be obtained. Reduce the number of Electroconvulsive treatments&#xD;
      and reduce the duration of treatment. However, the current literature has not yet verified&#xD;
      the clinical benefit of ketamine combine propofol as an anesthetic induction drug in patients&#xD;
      with schizophrenia who are receiving electroconvulsive therapy, and it is worthy of further&#xD;
      study.&#xD;
&#xD;
      In the investigator's clinical practice, the purpose of this experiment is to explore:&#xD;
      compared with propofol base anesthesia alone, and the combine use of ketamine and propofol&#xD;
      may reduce the threshold of seizure, improve the quality of Electroconvulsive therapy and&#xD;
      shorten the course of treatment. The combine use and titrate the drugs helps to reduce the&#xD;
      side effects of both ketamine and propofol (such as cardiovascular side effects and positive&#xD;
      symptoms) , achieve better Electroconvulsive therapy and effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Electroconvulsive therapy (ECT) serves as an effective adjuvant or alternative modality for&#xD;
      major depressive disorder, schizophrenia, or bipolar affective disorder refractory to or&#xD;
      contraindicated to psychopharmacological treatment. Anesthetics have been introduced into ECT&#xD;
      sessions to alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia,&#xD;
      hypertension, and anxiety.&#xD;
&#xD;
      Propofol is highly lipid soluble and able to rapidly cross the blood-brain barrier (BBB),&#xD;
      which leads to rapid onset of sedation and hypnosis. Meanwhile, propofol has hemodynamic&#xD;
      depressant effect and attenuates hypertensive surge during ECT. Characteristics mentioned&#xD;
      above make propofol one of widely used anesthetics for anesthetized ECT. However, propofol is&#xD;
      also well known for anticonvulsant property, which may inevitably interfere with seizure&#xD;
      propagation by electroconvulsive stimulus and diminish consequent efficacy. Thus, dosage of&#xD;
      electrical stimulus may be increased to achieve ideal seizure quality in this setting, which&#xD;
      also leads to higher risk of subsequent cognitive impairment or other complications.&#xD;
&#xD;
      Ketamine has also been widely used in the induction of anesthesia for the treatment of major&#xD;
      depressive disease in recent years. It has been found to increase the permeability and&#xD;
      therapeutic effect of antidepressants. Compared to traditional Barbiturate drugs or propofol,&#xD;
      do not increase the threshold of electricity required by electroporation, which can reduce&#xD;
      the time required for symptom relief of those drugs, It is a viable alternative induction&#xD;
      drug. However, ketamine causes short-term dissociative symptoms, which may temporarily&#xD;
      aggravate the positive symptoms of patients with schizophrenia after Electroconvulsive&#xD;
      therapy, but the time of aggravation of positive symptoms generally does not exceed 30&#xD;
      minutes.&#xD;
&#xD;
      There have been many studies in the clinic, and it has been confirmed that ketamine combine&#xD;
      propofol can be used for electroconvulsive treatment in patients with major depression and&#xD;
      bipolar disorder, and even better Electroconvulsive quality can be obtained. Reduce the&#xD;
      number of Electroconvulsive treatments and reduce the duration of treatment. However, the&#xD;
      current literature has not yet verified the clinical benefit of ketamine combine propofol as&#xD;
      an anesthetic induction drug in patients with schizophrenia who are receiving&#xD;
      electroconvulsive therapy, and it is worthy of further study.&#xD;
&#xD;
      In the investigator's clinical practice, the purpose of this experiment is to explore:&#xD;
      compared with propofol base anesthesia alone, and the combine use of ketamine and propofol&#xD;
      may reduce the threshold of seizure, improve the quality of Electroconvulsive therapy and&#xD;
      shorten the course of treatment. The combine use and titrate the drugs helps to reduce the&#xD;
      side effects of both ketamine and propofol (such as cardiovascular side effects and positive&#xD;
      symptoms) , achieve better Electroconvulsive therapy and effects.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">May 24, 2019</start_date>
  <completion_date type="Anticipated">April 20, 2021</completion_date>
  <primary_completion_date type="Anticipated">January 19, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The therapeutic effect after completing electroconvulsive treatment course</measure>
    <time_frame>At baseline, after 3rd course treatment(average 1-2 week), after 6th course treatment(average 2-4 week), after completion of treatment course( average 4-6 weeks, up to 8 weeks)</time_frame>
    <description>Record the change of disease illness, use The Clinical Global Impression - Improvement scale (CGI-I) and Clinical Global Impression - Severity scale (CGI-S) CGI-S(Severity) range 1-7 1: normal 7:extremely severe CGI-I(Improvement) range 1-7&#xD;
1:very much improved 7: vert much worse</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in Brief Psychiatric Rating Scale (BPRS)</measure>
    <time_frame>At baseline, after 3rd course treatment(average 1-2 week), after 6th course treatment(average 2-4 week), after completion of treatment course( average 4-6 weeks, up to 8 weeks)</time_frame>
    <description>Brief Psychiatric Rating Scale range:18-126&#xD;
Contains the following items:&#xD;
Somatic concern&#xD;
Anxiety&#xD;
Depression&#xD;
Suicidality&#xD;
Guilt&#xD;
Hostility&#xD;
Elated Mood&#xD;
Grandiosity&#xD;
Suspiciousness&#xD;
Hallucinations&#xD;
Unusual thought content&#xD;
Bizarre behaviour&#xD;
Self-neglect&#xD;
Disorientation&#xD;
Conceptual disorganisation&#xD;
Blunted affect&#xD;
Emotional withdrawal&#xD;
Motor retardation&#xD;
Tension&#xD;
Uncooperativeness&#xD;
Excitement&#xD;
Distractibility&#xD;
Motor hyperactivity&#xD;
Mannerisms and posturing Different item scores will have different results and outcomes&#xD;
&quot;&quot;Different values represent is not meaning a better or worse outcome, it must compare to the patient's status before&quot;&quot;</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">1</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>ketamine + propofol group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>use ketamine + propofol for ECT induction</description>
  </arm_group>
  <arm_group>
    <arm_group_label>propofol group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>use propofol only for ECT induction</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Propofol 10mg/ml IV push slowly 0.5-2mg/kg</description>
    <arm_group_label>ketamine + propofol group</arm_group_label>
    <arm_group_label>propofol group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ketamine</intervention_name>
    <description>Ketamine 50mg/ml IV push slowly 0.5- 1mg/kg</description>
    <arm_group_label>ketamine + propofol group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  The clinical diagnosis is consistent with the schizophrenia, and the diagnostic&#xD;
             requirements are in accordance with the Structural Diagnostic Interview Scale (SCID&#xD;
             for Diagnostic and Statistical Manual of Mental Disorders (DSM-5)) and are recognized&#xD;
             by psychiatrists as needing electroconvulsive therapy&#xD;
&#xD;
          -  Vision and hearing that can be operated normally or corrected&#xD;
&#xD;
          -  Subject consent form signed by the patient or agent&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Past or recent diagnosis of neurocognitive impairment&#xD;
&#xD;
          -  Contraindications for electroacupuncture treatment within one month, such as:&#xD;
             myocardial infarction, cerebrovascular disease, Increase Intracranial pressure,&#xD;
             cerebral hemangioma, untreated fracture, cervical spine injury, pheochromocytoma,&#xD;
             heart failure, severe heart valve disease, deep Venous embolism, etc&#xD;
&#xD;
          -  Untreated substances abuse disorder(eg illegal drugs, alcohol)&#xD;
&#xD;
          -  Unspecified mental disorder&#xD;
&#xD;
          -  PattientUnable to cooperate&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 13, 2019</study_first_submitted>
  <study_first_submitted_qc>February 1, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>May 26, 2019</last_update_submitted>
  <last_update_submitted_qc>May 26, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">May 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Electroconvulsive therapy</keyword>
  <keyword>ketamine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ketamine</mesh_term>
    <mesh_term>Propofol</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03829124
org study id: 201800056A3
nct id: NCT03829124
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
Electroconvulsive therapy (ECT) serves as an effective adjuvant modality for major depressive
      disorder, schizophrenia, or bipolar affective disorder refractory to or contraindicated to
      psychopharmacological treatment. Anesthetics have been introduced into ECT sessions to
      alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia, hypertension, and
      anxiety.

      Propofol is able to rapidly cross the blood-brain barrier (BBB), which leads to rapid onset
      of sedation and hypnosis. Meanwhile, propofol has hemodynamic depressant effect and
      attenuates hypertensive surge during ECT. Characteristics mentioned above make propofol one
      of widely used anesthetics for anesthetized ECT. However, propofol is also well known for
      anticonvulsant property. Thus, dosage of electrical stimulus may be increased to achieve
      ideal seizure quality in this setting, which also leads to higher risk of subsequent
      cognitive impairment or other complications.

      Ketamine has also been widely used in the induction of anesthesia for the treatment of major
      depressive disease in recent years. It has been found to increase the permeability and
      therapeutic effect of antidepressants. Compared to traditional Barbiturate drugs or propofol,
      do not increase the threshold of electricity required by electroporation, which can reduce
      the time required for symptom relief of those drugs, It is a viable alternative induction
      drug.

      There have been confirmed that ketamine combine propofol can be used for electroconvulsive
      treatment in patients with major depression and bipolar disorder, and even better
      Electroconvulsive quality can be obtained. Reduce the number of Electroconvulsive treatments
      and reduce the duration of treatment. However, the current literature has not yet verified
      the clinical benefit of ketamine combine propofol as an anesthetic induction drug in patients
      with schizophrenia who are receiving electroconvulsive therapy, and it is worthy of further
      study.

      In the investigator's clinical practice, the purpose of this experiment is to explore:
      compared with propofol base anesthesia alone, and the combine use of ketamine and propofol
      may reduce the threshold of seizure, improve the quality of Electroconvulsive therapy and
      shorten the course of treatment. The combine use and titrate the drugs helps to reduce the
      side effects of both ketamine and propofol (such as cardiovascular side effects and positive
      symptoms) , achieve better Electroconvulsive therapy and effects.
Electroconvulsive therapy (ECT) serves as an effective adjuvant or alternative modality for
      major depressive disorder, schizophrenia, or bipolar affective disorder refractory to or
      contraindicated to psychopharmacological treatment. Anesthetics have been introduced into ECT
      sessions to alleviate ECT-inducing discomfort sensation, tachycardia, arrhythmia,
      hypertension, and anxiety.

      Propofol is highly lipid soluble and able to rapidly cross the blood-brain barrier (BBB),
      which leads to rapid onset of sedation and hypnosis. Meanwhile, propofol has hemodynamic
      depressant effect and attenuates hypertensive surge during ECT. Characteristics mentioned
      above make propofol one of widely used anesthetics for anesthetized ECT. However, propofol is
      also well known for anticonvulsant property, which may inevitably interfere with seizure
      propagation by electroconvulsive stimulus and diminish consequent efficacy. Thus, dosage of
      electrical stimulus may be increased to achieve ideal seizure quality in this setting, which
      also leads to higher risk of subsequent cognitive impairment or other complications.

      Ketamine has also been widely used in the induction of anesthesia for the treatment of major
      depressive disease in recent years. It has been found to increase the permeability and
      therapeutic effect of antidepressants. Compared to traditional Barbiturate drugs or propofol,
      do not increase the threshold of electricity required by electroporation, which can reduce
      the time required for symptom relief of those drugs, It is a viable alternative induction
      drug. However, ketamine causes short-term dissociative symptoms, which may temporarily
      aggravate the positive symptoms of patients with schizophrenia after Electroconvulsive
      therapy, but the time of aggravation of positive symptoms generally does not exceed 30
      minutes.

      There have been many studies in the clinic, and it has been confirmed that ketamine combine
      propofol can be used for electroconvulsive treatment in patients with major depression and
      bipolar disorder, and even better Electroconvulsive quality can be obtained. Reduce the
      number of Electroconvulsive treatments and reduce the duration of treatment. However, the
      current literature has not yet verified the clinical benefit of ketamine combine propofol as
      an anesthetic induction drug in patients with schizophrenia who are receiving
      electroconvulsive therapy, and it is worthy of further study.

      In the investigator's clinical practice, the purpose of this experiment is to explore:
      compared with propofol base anesthesia alone, and the combine use of ketamine and propofol
      may reduce the threshold of seizure, improve the quality of Electroconvulsive therapy and
      shorten the course of treatment. The combine use and titrate the drugs helps to reduce the
      side effects of both ketamine and propofol (such as cardiovascular side effects and positive
      symptoms) , achieve better Electroconvulsive therapy and effects.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: The therapeutic effect after completing electroconvulsive treatment course
time frame: At baseline, after 3rd course treatment(average 1-2 week), after 6th course treatment(average 2-4 week), after completion of treatment course( average 4-6 weeks, up to 8 weeks)
description: Record the change of disease illness, use The Clinical Global Impression - Improvement scale (CGI-I) and Clinical Global Impression - Severity scale (CGI-S) CGI-S(Severity) range 1-7 1: normal 7:extremely severe CGI-I(Improvement) range 1-7
1:very much improved 7: vert much worse
measure: Change from baseline in Brief Psychiatric Rating Scale (BPRS)
time frame: At baseline, after 3rd course treatment(average 1-2 week), after 6th course treatment(average 2-4 week), after completion of treatment course( average 4-6 weeks, up to 8 weeks)
description: Brief Psychiatric Rating Scale range:18-126
Contains the following items:
Somatic concern
Anxiety
Depression
Suicidality
Guilt
Hostility
Elated Mood
Grandiosity
Suspiciousness
Hallucinations
Unusual thought content
Bizarre behaviour
Self-neglect
Disorientation
Conceptual disorganisation
Blunted affect
Emotional withdrawal
Motor retardation
Tension
Uncooperativeness
Excitement
Distractibility
Motor hyperactivity
Mannerisms and posturing Different item scores will have different results and outcomes
""Different values represent is not meaning a better or worse outcome, it must compare to the patient's status before""
arm group label: ketamine + propofol group
arm group type: Experimental
description: use ketamine + propofol for ECT induction
arm group label: propofol group
arm group type: Active Comparator
description: use propofol only for ECT induction
intervention type: Drug
intervention name: Propofol
description: Propofol 10mg/ml IV push slowly 0.5-2mg/kg
arm group label: ketamine + propofol group
arm group label: propofol group
intervention type: Drug
intervention name: Ketamine
description: Ketamine 50mg/ml IV push slowly 0.5- 1mg/kg
arm group label: ketamine + propofol group
criteria: 
gender: All
minimum age: 20 Years
maximum age: 65 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Ketamine
mesh term: Propofol
sharing ipd: No