xml: <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/NCT05978219</url>
    </required_header>
    <id_info>
      <org_study_id>2023/12</org_study_id>
      <nct_id>NCT05978219</nct_id>
    </id_info>
    <brief_title>Efficacy of Mirtazapine in Major Depressive Disorder With Insomnia</brief_title>
    <official_title>Efficacy of Mirtazapine in Major Depressive Disorder With Insomnia: A 6-Week Pre and Post Intervention Study</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>National Institute of Mental Health, Dhaka</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Sun Pharmaceutical Industries Limited</agency>
        <agency_class>Industry</agency_class>
      </collaborator>
    </sponsors>
    <source>National Institute of Mental Health, Dhaka</source>
    <oversight_info>
      <has_dmc>Yes</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>
        This will be a single center, prospective, open label, quasi-experimental pre-post&#xD;
        intervention trial in major depressive disorder (MDD) patients with insomnia.&#xD;
  &#xD;
        The main objectives are i. to assess efficacy of mirtazapine in reducing depression and&#xD;
        insomnia symptom severity in major depressive disorder (MDD) patients with insomnia.&#xD;
  &#xD;
        ii. to evaluate side effects of mirtazapine.&#xD;
  &#xD;
        Following enrollment and baseline assessment patients will be prescribed mirtazapine at 15-30&#xD;
        mg/day. Depending on the response, doses will be adjusted after two weeks and might be&#xD;
        titrated up to 45 mg/day.&#xD;
  &#xD;
        Each patient will be monitored for 42 days and assessment will be carried out on Day 0, Day&#xD;
        14, Day 28 and Day 42 of the trial.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Background: Mirtazapine is an atypical antidepressant acts by increasing noradrenergic and&#xD;
        serotonergic neurotransmission. It inhibits presynaptic adrenergic alpha-2 receptor along&#xD;
        with inhibition of postsynaptic serotonergic 5-HT2 and 5-HT3 receptors and histamine (H1)&#xD;
        receptor (Jilani et al., 2022). It was approved by FDA in 1996 for treating moderate and&#xD;
        severe depression; but it also has sedative, antiemetic, anxiolytic, and appetite stimulant&#xD;
        effects and for these prescribed in many other psychiatric disorders (Nutt, 2002). Because of&#xD;
        its efficacy, safety and tolerability, it is one of the drugs recommended by NICE to consider&#xD;
        as first-choice in treating depression (Middleton et al., 2005).&#xD;
  &#xD;
        A depressive episode is characterized by a period of depressed mood or diminished interest in&#xD;
        activities occurring most of the day, nearly every day during a period lasting at least two&#xD;
        weeks accompanied by other symptoms such as difficulty concentrating, feelings of&#xD;
        worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death&#xD;
        or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced&#xD;
        energy or fatigue. There have never been any prior manic, hypomanic, or mixed episodes, which&#xD;
        would indicate the presence of a bipolar disorder (ICD-11, 2019).&#xD;
  &#xD;
        Around 6.7% of adult population in Bangladesh suffers from depressive disorders (NIMH, 2019).&#xD;
        However, no interventional study has yet been carried out to see efficacy of different&#xD;
        antidepressants in this population. As one of the frequently observed features of depression&#xD;
        is insomnia, mirtazapine could be a good choice in these cases. This study intends to assess&#xD;
        the efficacy of mirtazapine in major depressive disorder when the patients also present with&#xD;
        insomnia.&#xD;
  &#xD;
        General objective To assess the efficacy of mirtazapine in reducing depression with insomnia&#xD;
        symptoms in patients with major depressive disorder (MDD) with insomnia.&#xD;
  &#xD;
        Specific objectives&#xD;
  &#xD;
          1. To assess the efficacy of mirtazapine in reducing depressive symptoms in patients with&#xD;
             MDD with insomnia.&#xD;
  &#xD;
          2. To assess the efficacy of mirtazapine in reducing insomnia symptoms in patients with MDD&#xD;
             with insomnia.&#xD;
  &#xD;
          3. To compare the quality of life in patients with MDD before and after introducing&#xD;
             mirtazapine.&#xD;
  &#xD;
          4. To assess the side-effects experienced by trial patients.&#xD;
  &#xD;
        Methods: This will be a single center, prospective, open label, quasi-experimental pre-post&#xD;
        intervention trial in MDD patients with insomnia. The study will be conducted at National&#xD;
        Institute of Mental Health (NIMH), Bangladesh over a period of 8 months. A total of 135 MDD&#xD;
        patients with insomnia who fulfill the selection criteria will be conveniently selected for&#xD;
        the study. Following enrollment and baseline assessment patients will be prescribed&#xD;
        mirtazapine at 15-30 mg/day. Depending on the response, doses will be adjusted after two&#xD;
        weeks and might be titrated up to 45 mg/day.&#xD;
  &#xD;
        Each patient will be monitored for 42 days and assessment will be carried out on Day 0, Day&#xD;
        14, Day 28 and Day 42 of the trial. A semi-structured clinical information questionnaire,&#xD;
        Hamilton Depression Rating Scale (HDRS), Insomnia Severity Index (ISI), Antidepressant&#xD;
        Side-Effect Checklist (ASEC), World Health Organization Quality of Life (WHOQOL-BREF) will be&#xD;
        used by research psychiatrists during assessment.&#xD;
  &#xD;
        The whole study will be on accordance with Helsinki Declaration and prior to commencement,&#xD;
        ethical approval will be taken from IRB and Bangladesh Medical Research Council (BMRC). The&#xD;
        protocol will also be registered with the International Clinical Trials Registry Platform&#xD;
        (ICTRP).&#xD;
  &#xD;
        Potential significance: The findings will generate information on efficacy of mirtazapine in&#xD;
        reducing depressive and insomnia symptom severity in MDD patients with insomnia and regarding&#xD;
        side effects of mirtazapine in Bangladeshi adult population.&#xD;
  &#xD;
        Funding: This study is conceptualized and sponsored by Bangladesh Association of&#xD;
        Psychiatrists (BAP) with scientific support and research grant from Sun Pharmaceutical&#xD;
        Bangladesh Ltd.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 25, 2023</start_date>
    <completion_date type="Anticipated">February 28, 2024</completion_date>
    <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
    <phase>Phase 4</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>Quasi-experimental pre-post intervention trial</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Change from baseline in mean Hamilton Depression Rating Scale score</measure>
      <time_frame>At Day 0, Day 14 and Day 42</time_frame>
      <description>Hamilton Depression Rating Scale is one of the most widely used clinician-administered depression assessment scale. The 17-item version score ranges between 0-53 with higher score indicates worse outcome.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in mean Insomnia Severity Index score</measure>
      <time_frame>At Day 0, Day 14 and Day 42</time_frame>
      <description>The Insomnia Severity Scale is a 7-item and 5-point Likert self-report questionnaire which is used to assess the nature, severity, and impact of insomnia. The total score can be between 0-35 and higher score indicates worse outcome.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Frequency and severity of side effects experienced by trial patients as measured by Antidepressant Side-Effect Checklist</measure>
      <time_frame>Day 14 and Day 42</time_frame>
      <description>This is a self-reporting side-effect checklist developed by Royal College of the Psychiatrist for those taking antidepressants. There are 21 items each mentioning a particular side effect and for each item, the participants rated the severity of the specified symptom on a four-point scale (0 absent; 1 mild; 2 moderate; 3 severe) and specified whether a symptom (if present) was likely to be a side-effect of the antidepressant drug (yes or no).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Change from baseline in mean World Health Organization Quality of Life score</measure>
      <time_frame>Day 0 and Day 42</time_frame>
      <description>The WHOQOL-BREF is a 26-item questionnaire in a Likert scale format that assesses individuals' perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The 26 items can be answered in a 1-5 Likert scale format; The scale is scored by adding up the score on each item to yield a total score for the instrument. It assesses quality of life in four domains namely physical, psychological, social and environmental. The converted scores for each domain range between 0-100 and a higher score indicates higher quality of life in that domain.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">135</enrollment>
    <condition>Major Depressive Disorder With Insomnia</condition>
    <arm_group>
      <arm_group_label>Patients with MDD with insomnia</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Diagnosed MDD patients with insomnia problems will be approached and enrolled from NIMH, Dhaka.&#xD;
  Trial medications will be self-administered and treatment regimen will be continued until serious adverse effect develops or for 42 days, whichever occurs sooner.&#xD;
  Patients will receive mirtazapine at 15-30 mg/day (tablet form, once or twice daily, orally) from start. Depending on the response, doses might be increased at 2 weeks up to 45 mg/day for mirtazapine.&#xD;
  The clinical trial for each patient will last for 42 days. Clinical data will be collected at the beginning - Day 0 and then on Day 14 and Day 42 of the trial by face-to-face interview. A clinical follow up will be provided to trial patients on Day 28 of the trial over telephone. Research psychiatrists will also conduct follow up, medication and side effect monitoring and overall management of the patients.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>Mirtazapine Tablets</intervention_name>
      <description>Mirtazapine tablet form, orally, once or twice daily, 15-45 mg</description>
      <arm_group_label>Patients with MDD with insomnia</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Age 18-60 years.&#xD;
  &#xD;
            2. Diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, 5th&#xD;
               Edition (DSM-5) for MDD.&#xD;
  &#xD;
            3. A ≥20 total score on the 17-item Hamilton depression rating scale (HDRS).&#xD;
  &#xD;
            4. A ≥15 total score on the 7-item Insomnia Severity Index (ISI).&#xD;
  &#xD;
            5. Considered to require antidepressant treatment based on the judgment of the consulting&#xD;
               psychiatrist.&#xD;
  &#xD;
            6. For women - willing to abstain from conception or willing to use modern method of&#xD;
               contraception (she or her partner) during trial period.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. History of use of mirtazapine in the last 3 months period.&#xD;
  &#xD;
            2. Pregnant or breastfeeding mother.&#xD;
  &#xD;
            3. At significant risk for suicide.&#xD;
  &#xD;
            4. Diagnosed with a primary condition including dementia as well as bipolar,&#xD;
               obsessive-compulsive, or eating disorders, schizophrenia, or alcohol or substance&#xD;
               dependence except for tobacco dependence.&#xD;
  &#xD;
            5. Experiencing any medical conditions judged to render the patient ineligible to&#xD;
               participate in the study.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>60 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Mohammad Tariqul Alam, FCPS</last_name>
      <phone>+8801818222228</phone>
      <email>sum.tariq@gmail.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Ahsan Aziz Sarkar, FCPS</last_name>
      <phone>+8801795230466</phone>
      <email>ahsan.psychiatry@gmail.com</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>National Institute of Mental Health</name>
        <address>
          <city>Dhaka</city>
          <zip>1207</zip>
          <country>Bangladesh</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Mohammad Tariqul Alam, FCPS</last_name>
        <phone>+8801818222228</phone>
        <email>sum.tariq@gmail.com</email>
      </contact>
      <investigator>
        <last_name>Mohammad Tariqul Alam, FCPS</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Helel Uddin Ahmed, MD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Muhammad Zillur Rahman Khan, FCPS</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Ahsan Aziz Sarkar, FCPS</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>Bangladesh</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>July 28, 2023</study_first_submitted>
    <study_first_submitted_qc>July 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>August 4, 2023</last_update_submitted>
    <last_update_submitted_qc>August 4, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>National Institute of Mental Health, Dhaka</investigator_affiliation>
      <investigator_full_name>Dr. Ahsan Aziz Sarkar</investigator_full_name>
      <investigator_title>Co-investigator</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Sleep Initiation and Maintenance Disorders</mesh_term>
      <mesh_term>Depressive Disorder</mesh_term>
      <mesh_term>Depression</mesh_term>
      <mesh_term>Depressive Disorder, Major</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Mirtazapine</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT05978219
  org study id: 2023/12
  nct id: NCT05978219
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  is us export: No
  This will be a single center, prospective, open label, quasi-experimental pre-post
        intervention trial in major depressive disorder (MDD) patients with insomnia.
  
        The main objectives are i. to assess efficacy of mirtazapine in reducing depression and
        insomnia symptom severity in major depressive disorder (MDD) patients with insomnia.
  
        ii. to evaluate side effects of mirtazapine.
  
        Following enrollment and baseline assessment patients will be prescribed mirtazapine at 15-30
        mg/day. Depending on the response, doses will be adjusted after two weeks and might be
        titrated up to 45 mg/day.
  
        Each patient will be monitored for 42 days and assessment will be carried out on Day 0, Day
        14, Day 28 and Day 42 of the trial.
  Background: Mirtazapine is an atypical antidepressant acts by increasing noradrenergic and
        serotonergic neurotransmission. It inhibits presynaptic adrenergic alpha-2 receptor along
        with inhibition of postsynaptic serotonergic 5-HT2 and 5-HT3 receptors and histamine (H1)
        receptor (Jilani et al., 2022). It was approved by FDA in 1996 for treating moderate and
        severe depression; but it also has sedative, antiemetic, anxiolytic, and appetite stimulant
        effects and for these prescribed in many other psychiatric disorders (Nutt, 2002). Because of
        its efficacy, safety and tolerability, it is one of the drugs recommended by NICE to consider
        as first-choice in treating depression (Middleton et al., 2005).
  
        A depressive episode is characterized by a period of depressed mood or diminished interest in
        activities occurring most of the day, nearly every day during a period lasting at least two
        weeks accompanied by other symptoms such as difficulty concentrating, feelings of
        worthlessness or excessive or inappropriate guilt, hopelessness, recurrent thoughts of death
        or suicide, changes in appetite or sleep, psychomotor agitation or retardation, and reduced
        energy or fatigue. There have never been any prior manic, hypomanic, or mixed episodes, which
        would indicate the presence of a bipolar disorder (ICD-11, 2019).
  
        Around 6.7% of adult population in Bangladesh suffers from depressive disorders (NIMH, 2019).
        However, no interventional study has yet been carried out to see efficacy of different
        antidepressants in this population. As one of the frequently observed features of depression
        is insomnia, mirtazapine could be a good choice in these cases. This study intends to assess
        the efficacy of mirtazapine in major depressive disorder when the patients also present with
        insomnia.
  
        General objective To assess the efficacy of mirtazapine in reducing depression with insomnia
        symptoms in patients with major depressive disorder (MDD) with insomnia.
  
        Specific objectives
  
          1. To assess the efficacy of mirtazapine in reducing depressive symptoms in patients with
             MDD with insomnia.
  
          2. To assess the efficacy of mirtazapine in reducing insomnia symptoms in patients with MDD
             with insomnia.
  
          3. To compare the quality of life in patients with MDD before and after introducing
             mirtazapine.
  
          4. To assess the side-effects experienced by trial patients.
  
        Methods: This will be a single center, prospective, open label, quasi-experimental pre-post
        intervention trial in MDD patients with insomnia. The study will be conducted at National
        Institute of Mental Health (NIMH), Bangladesh over a period of 8 months. A total of 135 MDD
        patients with insomnia who fulfill the selection criteria will be conveniently selected for
        the study. Following enrollment and baseline assessment patients will be prescribed
        mirtazapine at 15-30 mg/day. Depending on the response, doses will be adjusted after two
        weeks and might be titrated up to 45 mg/day.
  
        Each patient will be monitored for 42 days and assessment will be carried out on Day 0, Day
        14, Day 28 and Day 42 of the trial. A semi-structured clinical information questionnaire,
        Hamilton Depression Rating Scale (HDRS), Insomnia Severity Index (ISI), Antidepressant
        Side-Effect Checklist (ASEC), World Health Organization Quality of Life (WHOQOL-BREF) will be
        used by research psychiatrists during assessment.
  
        The whole study will be on accordance with Helsinki Declaration and prior to commencement,
        ethical approval will be taken from IRB and Bangladesh Medical Research Council (BMRC). The
        protocol will also be registered with the International Clinical Trials Registry Platform
        (ICTRP).
  
        Potential significance: The findings will generate information on efficacy of mirtazapine in
        reducing depressive and insomnia symptom severity in MDD patients with insomnia and regarding
        side effects of mirtazapine in Bangladeshi adult population.
  
        Funding: This study is conceptualized and sponsored by Bangladesh Association of
        Psychiatrists (BAP) with scientific support and research grant from Sun Pharmaceutical
        Bangladesh Ltd.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: Quasi-experimental pre-post intervention trial
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Change from baseline in mean Hamilton Depression Rating Scale score
  time frame: At Day 0, Day 14 and Day 42
  description: Hamilton Depression Rating Scale is one of the most widely used clinician-administered depression assessment scale. The 17-item version score ranges between 0-53 with higher score indicates worse outcome.
  measure: Change from baseline in mean Insomnia Severity Index score
  time frame: At Day 0, Day 14 and Day 42
  description: The Insomnia Severity Scale is a 7-item and 5-point Likert self-report questionnaire which is used to assess the nature, severity, and impact of insomnia. The total score can be between 0-35 and higher score indicates worse outcome.
  measure: Frequency and severity of side effects experienced by trial patients as measured by Antidepressant Side-Effect Checklist
  time frame: Day 14 and Day 42
  description: This is a self-reporting side-effect checklist developed by Royal College of the Psychiatrist for those taking antidepressants. There are 21 items each mentioning a particular side effect and for each item, the participants rated the severity of the specified symptom on a four-point scale (0 absent; 1 mild; 2 moderate; 3 severe) and specified whether a symptom (if present) was likely to be a side-effect of the antidepressant drug (yes or no).
  measure: Change from baseline in mean World Health Organization Quality of Life score
  time frame: Day 0 and Day 42
  description: The WHOQOL-BREF is a 26-item questionnaire in a Likert scale format that assesses individuals' perceptions of their position in life in the context of the culture and value systems in which they live and in relation to their goals, expectations, standards and concerns. The 26 items can be answered in a 1-5 Likert scale format; The scale is scored by adding up the score on each item to yield a total score for the instrument. It assesses quality of life in four domains namely physical, psychological, social and environmental. The converted scores for each domain range between 0-100 and a higher score indicates higher quality of life in that domain.
  arm group label: Patients with MDD with insomnia
  arm group type: Experimental
  description: Diagnosed MDD patients with insomnia problems will be approached and enrolled from NIMH, Dhaka.
  Trial medications will be self-administered and treatment regimen will be continued until serious adverse effect develops or for 42 days, whichever occurs sooner.
  Patients will receive mirtazapine at 15-30 mg/day (tablet form, once or twice daily, orally) from start. Depending on the response, doses might be increased at 2 weeks up to 45 mg/day for mirtazapine.
  The clinical trial for each patient will last for 42 days. Clinical data will be collected at the beginning - Day 0 and then on Day 14 and Day 42 of the trial by face-to-face interview. A clinical follow up will be provided to trial patients on Day 28 of the trial over telephone. Research psychiatrists will also conduct follow up, medication and side effect monitoring and overall management of the patients.
  intervention type: Drug
  intervention name: Mirtazapine Tablets
  description: Mirtazapine tablet form, orally, once or twice daily, 15-45 mg
  arm group label: Patients with MDD with insomnia
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 60 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Mohammad Tariqul Alam, FCPS
  phone: +8801818222228
  email: sum.tariq@gmail.com
  last name: Ahsan Aziz Sarkar, FCPS
  phone: +8801795230466
  email: ahsan.psychiatry@gmail.com
  facility: 
  status: Recruiting
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: Bangladesh
  responsible party type: Principal Investigator
  investigator affiliation: National Institute of Mental Health, Dhaka
  investigator full name: Dr. Ahsan Aziz Sarkar
  investigator title: Co-investigator
  mesh term: Sleep Initiation and Maintenance Disorders
  mesh term: Depressive Disorder
  mesh term: Depression
  mesh term: Depressive Disorder, Major
  mesh term: Mirtazapine
  sharing ipd: Undecided