<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/NCT03248180</url>
  </required_header>
  <id_info>
    <org_study_id>201703002MIND</org_study_id>
    <nct_id>NCT03248180</nct_id>
  </id_info>
  <brief_title>Guided Dose Reduction of Antipsychotic in Patients With Psychosis in Remitted States</brief_title>
  <acronym>GDR</acronym>
  <official_title>Impact of Guided Antipsychotic Dose Reduction in Patients With Psychosis Under Remitted States: a Randomized Control Trial and Prospective Follow-up Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A 2-year prospective observational study comparing a group of patients in remitted states of&#xD;
      psychosis undergoing guided antipsychotic dose reduction to a similar group of patients under&#xD;
      maintenance antipsychotic treatment with the main outcome of interest that if the rates of&#xD;
      relapse of psychosis between these two groups will be different.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Early intervention at the beginning of schizophrenia and related psychotic disorders can get&#xD;
      better treatment response. Once symptoms subsided, the majority of patients wish to&#xD;
      discontinue medications, yet currently the mainstream opinions still recommend maintenance&#xD;
      antipsychotic therapy because non-adherence to medication is the most significant risk factor&#xD;
      to predict a relapse. However, recent longitudinal studies assessing patients in community&#xD;
      for a longer term found that their functioning is not necessarily poorer despite not&#xD;
      regularly treated with antipsychotics. Also there are studies suggesting a lower percentage&#xD;
      of dopamine occupancy by antipsychotic is acceptable in stable patients with psychosis. To&#xD;
      elucidate such discrepancies, a hypothetical compromised approach &quot;guided dose reduction, but&#xD;
      not aiming at discontinuation&quot;is proposed. In this study, we will recruit outpatients with&#xD;
      schizophrenia related psychotic disorders under remitted states, randomize into guided dose&#xD;
      reduction group (GDR, n = 80) and maintenance treatment group (MTG), including those who&#xD;
      willing to have dose reduction but assigned to maintenance group (MTG1, n = 40) and those who&#xD;
      willing to continue medication serving as naturalistic observation group (MTG2, n = 40), and&#xD;
      follow up for at least 2 years. The main outcomes of interests are differences in relapse&#xD;
      rates, personal social performance, quality of life, drug-related adverse reactions,&#xD;
      medication satisfaction, and neurocognitive function between groups.We will also have&#xD;
      patients to keep logs of medication status, blood tests for therapeutic drug monitoring,&#xD;
      biochemistry, and potential biomarkers, as well as take into account demographic variables&#xD;
      such as age, gender, education, employment status, and supportive system, and clinical&#xD;
      variables such as age of onset, duration of illness, history of psychiatric admission, the&#xD;
      highest and the lowest doses of antipsychotics during previous treatment, the number of&#xD;
      different antipsychotics having being tried before, if a history of impending relapse during&#xD;
      tapering down dose of antipsychotics, and concomitant psychotropic agents, to test whether&#xD;
      these variables are related to outcomes during follow-up. Hopefully we can identify a&#xD;
      satisfactory and balanced solution between improving patient's psychosocial and&#xD;
      neurocognitive outcomes and prevention of relapse by redefining the role of antipsychotics.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">July 24, 2017</start_date>
  <completion_date type="Anticipated">December 31, 2020</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2020</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Relapse of psychosis defined by worsening of scores in Positive and Negative Syndrome Scale (PANSS)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Patients will be measured with a Positive and Negative Syndrome Scale (PANSS) every 4 weeks for 3 times (during 12 weeks) if conducting dose reduction or every 12 weeks if staying on the same dose to observe if any worsening of symptoms. Patient has a PANSS score &gt; 4 in any item of those 3 positive symptoms (P1: delusion, P2: conceptual disorganization, P3: hallucination) and 2 general symptoms (G9: unusual thought, G5:mannerism and posturing) during observational period for more than 1 week will be recognized as having a relapse of psychosis.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Personal Social Performance (PSP) scores</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Patients will be rated by their attending psychiatrists with PSP scale to evaluate their functioning in 4 aspects of life, including socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behaviors as to give a summary score at baseline and annually</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>quality of life (Euro-5D VAS)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Patients report their quality of life using a 20-cm visual analogue at baseline and annually.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>severity of extrapyramidal symptoms</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Patient's severity of extrapyramidal symptoms will be rated by their psychiatrists using Simpson-Angus Scale, the Abnormal Involuntary Movement Scale, and the Barnes Akathisia Rating Scale at each visit.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>medication satisfaction questionnaire (MSQ)</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Patients will be asked to fill a self-rated 7-point Likert scale for medication satisfaction at baseline and annually.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>neurocognitive functioning</measure>
    <time_frame>up to 2 years</time_frame>
    <description>Patients will be assessed with the module for schizophrenia of the Cambridge Neuropsychological Test Automatic Battery (Cantab) at baseline and at the exit of the study.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">160</enrollment>
  <condition>Psychosis</condition>
  <condition>Remission</condition>
  <arm_group>
    <arm_group_label>Guided dose reduction (GDR)</arm_group_label>
    <description>Patients in the GDR group will be advised to reduce &lt; 25% of their current dose of antipsychotic agents estimated on a weekly base and follow-up every 4 weeks for at least 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Maintenance treatment group (MTG)</arm_group_label>
    <description>Patients in the MTG will be advised to stay on their current dose of antipsychotics throughout the observational period, follow-up every 12 weeks.</description>
  </arm_group>
  <biospec_retention>Samples Without DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      plasma for determining concentration of antipsychotics&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Outpatients received follow-up at or referred to the study hospital&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. A diagnosis of schizophrenia, schizophreniform disorder, psychosis NOS, based on the&#xD;
             DSM-5 criteria&#xD;
&#xD;
          2. With a Positive and Negative Syndrome Scale (PANSS), score &lt; 3 in all 3 positive&#xD;
             symptoms (P1: delusion, P2: conceptual disorganization, P3: hallucination) and 2&#xD;
             general symptoms (G9: unusual thought, G5: mannerism and posturing) for at least 3&#xD;
             months&#xD;
&#xD;
          3. With a PANSS score &lt; 4 in all 3 negative symptoms (N1: blunted affect, N4: social&#xD;
             withdrawal, N6: lack of spontaneity/flow in conversation) for at least 3 months&#xD;
&#xD;
          4. Currently receiving antipsychotic treatment at a fixed dose for at least 3 months,&#xD;
             including long-acting injectable antipsychotic&#xD;
&#xD;
          5. A second antipsychotic agent only used for a low-dose, as needed adjuvant purpose&#xD;
&#xD;
          6. No revised use of benzodiazepines, antidepressants, anticholinergics, or other&#xD;
             concomitant medications during past 3 months -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A score of 5 or more on any of the 30 PANSS rating items at screening&#xD;
&#xD;
          2. Admission to acute psychiatric unit during past 6 months&#xD;
&#xD;
          3. A change in dose of current antipsychotic medication in recent 3 months&#xD;
&#xD;
          4. Concomitant use of mood stabilizers, such as lithium, valproic acid or other&#xD;
             anti-epileptic drugs&#xD;
&#xD;
          5. Mental retardation known as IQ below 70 prior to the diagnosis of schizophrenia&#xD;
&#xD;
          6. A history of pervasive mental disorder or bipolar disorder&#xD;
&#xD;
          7. A medical condition with significant cognitive sequelae&#xD;
&#xD;
          8. A history of substance dependence during past 6 months&#xD;
&#xD;
          9. Currently in pregnancy or breastfeeding&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chen-Chung Liu, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>National Taiwan University Hospital</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chen-Chung Liu, MD, PhD</last_name>
    <phone>886-2-23123456</phone>
    <phone_ext>66130</phone_ext>
    <email>chchliu@ntu.edu.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <zip>100</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chen-Chung Liu, MD, PhD</last_name>
      <phone>886-2-23123456</phone>
      <phone_ext>66130</phone_ext>
      <email>chchliu@ntu.edu.tw</email>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2017</verification_date>
  <study_first_submitted>August 6, 2017</study_first_submitted>
  <study_first_submitted_qc>August 9, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 14, 2017</study_first_posted>
  <last_update_submitted>August 9, 2017</last_update_submitted>
  <last_update_submitted_qc>August 9, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">August 14, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>antipsychotic</keyword>
  <keyword>guided dose reduction</keyword>
  <keyword>maintenance treatment</keyword>
  <keyword>remitted psychosis</keyword>
  <keyword>relapse</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Psychotic Disorders</mesh_term>
    <mesh_term>Mental Disorders</mesh_term>
  </condition_browse>
  <!-- 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/NCT03248180
org study id: 201703002MIND
nct id: NCT03248180
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
A 2-year prospective observational study comparing a group of patients in remitted states of
      psychosis undergoing guided antipsychotic dose reduction to a similar group of patients under
      maintenance antipsychotic treatment with the main outcome of interest that if the rates of
      relapse of psychosis between these two groups will be different.
Early intervention at the beginning of schizophrenia and related psychotic disorders can get
      better treatment response. Once symptoms subsided, the majority of patients wish to
      discontinue medications, yet currently the mainstream opinions still recommend maintenance
      antipsychotic therapy because non-adherence to medication is the most significant risk factor
      to predict a relapse. However, recent longitudinal studies assessing patients in community
      for a longer term found that their functioning is not necessarily poorer despite not
      regularly treated with antipsychotics. Also there are studies suggesting a lower percentage
      of dopamine occupancy by antipsychotic is acceptable in stable patients with psychosis. To
      elucidate such discrepancies, a hypothetical compromised approach "guided dose reduction, but
      not aiming at discontinuation"is proposed. In this study, we will recruit outpatients with
      schizophrenia related psychotic disorders under remitted states, randomize into guided dose
      reduction group (GDR, n = 80) and maintenance treatment group (MTG), including those who
      willing to have dose reduction but assigned to maintenance group (MTG1, n = 40) and those who
      willing to continue medication serving as naturalistic observation group (MTG2, n = 40), and
      follow up for at least 2 years. The main outcomes of interests are differences in relapse
      rates, personal social performance, quality of life, drug-related adverse reactions,
      medication satisfaction, and neurocognitive function between groups.We will also have
      patients to keep logs of medication status, blood tests for therapeutic drug monitoring,
      biochemistry, and potential biomarkers, as well as take into account demographic variables
      such as age, gender, education, employment status, and supportive system, and clinical
      variables such as age of onset, duration of illness, history of psychiatric admission, the
      highest and the lowest doses of antipsychotics during previous treatment, the number of
      different antipsychotics having being tried before, if a history of impending relapse during
      tapering down dose of antipsychotics, and concomitant psychotropic agents, to test whether
      these variables are related to outcomes during follow-up. Hopefully we can identify a
      satisfactory and balanced solution between improving patient's psychosocial and
      neurocognitive outcomes and prevention of relapse by redefining the role of antipsychotics.
observational model: Case-Control
time perspective: Prospective
measure: Relapse of psychosis defined by worsening of scores in Positive and Negative Syndrome Scale (PANSS)
time frame: up to 2 years
description: Patients will be measured with a Positive and Negative Syndrome Scale (PANSS) every 4 weeks for 3 times (during 12 weeks) if conducting dose reduction or every 12 weeks if staying on the same dose to observe if any worsening of symptoms. Patient has a PANSS score > 4 in any item of those 3 positive symptoms (P1: delusion, P2: conceptual disorganization, P3: hallucination) and 2 general symptoms (G9: unusual thought, G5:mannerism and posturing) during observational period for more than 1 week will be recognized as having a relapse of psychosis.
measure: Personal Social Performance (PSP) scores
time frame: up to 2 years
description: Patients will be rated by their attending psychiatrists with PSP scale to evaluate their functioning in 4 aspects of life, including socially useful activities, personal and social relationships, self-care, and disturbing and aggressive behaviors as to give a summary score at baseline and annually
measure: quality of life (Euro-5D VAS)
time frame: up to 2 years
description: Patients report their quality of life using a 20-cm visual analogue at baseline and annually.
measure: severity of extrapyramidal symptoms
time frame: up to 2 years
description: Patient's severity of extrapyramidal symptoms will be rated by their psychiatrists using Simpson-Angus Scale, the Abnormal Involuntary Movement Scale, and the Barnes Akathisia Rating Scale at each visit.
measure: medication satisfaction questionnaire (MSQ)
time frame: up to 2 years
description: Patients will be asked to fill a self-rated 7-point Likert scale for medication satisfaction at baseline and annually.
measure: neurocognitive functioning
time frame: up to 2 years
description: Patients will be assessed with the module for schizophrenia of the Cambridge Neuropsychological Test Automatic Battery (Cantab) at baseline and at the exit of the study.
arm group label: Guided dose reduction (GDR)
description: Patients in the GDR group will be advised to reduce < 25% of their current dose of antipsychotic agents estimated on a weekly base and follow-up every 4 weeks for at least 12 weeks.
arm group label: Maintenance treatment group (MTG)
description: Patients in the MTG will be advised to stay on their current dose of antipsychotics throughout the observational period, follow-up every 12 weeks.
plasma for determining concentration of antipsychotics
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: No
last name: Chen-Chung Liu, MD, PhD
role: Principal Investigator
affiliation: National Taiwan University Hospital
last name: Chen-Chung Liu, MD, PhD
phone: 886-2-23123456
phone ext: 66130
email: chchliu@ntu.edu.tw
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Psychotic Disorders
mesh term: Mental Disorders