<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/NCT02219880</url>
  </required_header>
  <id_info>
    <org_study_id>137/14</org_study_id>
    <nct_id>NCT02219880</nct_id>
  </id_info>
  <brief_title>Kava for the Treatment of Generalised Anxiety Disorder: A Double-Blind Randomised Placebo-Controlled Trial</brief_title>
  <acronym>KGAD</acronym>
  <official_title>Kava for the Treatment of Generalised Anxiety Disorder: A Double-Blind Randomised Placebo-Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Melbourne</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Swinburne University of Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The University of Queensland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Melbourne</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The use of Kava in Generalised Anxiety Disorder: an 18-week double-blind, randomised,&#xD;
      placebo-controlled study.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The primary aim is to confirm the efficacy and safety of Kava compared to placebo in&#xD;
      Generalized Anxiety Disorder (GAD). Secondary aims of the study are to confirm the&#xD;
      relationship between specific genetic variations and response to Kava, and to explore the&#xD;
      effects of Kava on the expression of specific genes.&#xD;
&#xD;
      Consenting participants will be randomly allocated to take either Kava or placebo over 18&#xD;
      weeks. They will be assessed at regular interviews throughout the trial and will have four&#xD;
      blood tests (liver function tests to monitor participant safety, and collection of genetic&#xD;
      material providing information on neurochemistry). The design of the study is a multi-centre,&#xD;
      18-week, 2-arm, double-blind randomised clinical trial (RCT) using a standardised&#xD;
      pharmaceutical-grade water-soluble extract of Kava (240mg of kavalactones per day) versus&#xD;
      placebo in 210 adults with GAD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 13, 2015</start_date>
  <completion_date type="Actual">May 31, 2018</completion_date>
  <primary_completion_date type="Actual">May 31, 2018</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>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Hamilton Anxiety Rating Scale (HAMA) - change in score</measure>
    <time_frame>18 weeks</time_frame>
    <description>Reduction of participant's anxiety will be assessed on the HAMA from baseline to week 16 across time used a mixed methods model.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gamma-aminobutyric acid (GABA) transporter polymorphisms moderating response to study intervention</measure>
    <time_frame>18 weeks</time_frame>
    <description>Will assess whether response to Kava will be moderated by gamma-aminobutyric acid (GABA) transporter polymorphisms. Specifically, whether rs2601126-T allele or rs2697153-A allele carriers have greater reduction of anxiety</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Changes in score to psychometric questionnaire measures</measure>
    <time_frame>18 weeks</time_frame>
    <description>Depressive symptoms on the Montgomery-Asberg Depression Rating Scale (MADRS), self-rated anxiety on the Beck Anxiety Inventory (BAI), pathological worry on the Penn State Worry Questionnaire (PSWQ), and health-related quality of life on the Short Form Survey-12 (SF-12) will also be significantly improved by Kava over placebo; and</description>
  </other_outcome>
  <other_outcome>
    <measure>Monoamine and GABA differential gene expression</measure>
    <time_frame>8 weeks</time_frame>
    <description>Differential gene expression will be assessed from baseline to week 8 from participants in the Melbourne site. This will determine whether Kava increases expression of genes effecting expression of neurochemical e.g. GABA, and monoamines</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">178</enrollment>
  <condition>Generalized Anxiety Disorder</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Inert tablets matched for colour, size and consistency to active arm treatment. Both treatment arm tablets will match in appearance, and neither participants nor the trial clinicians will know what they are taking.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Kava - standardised 240mg kavalactones</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Standardised 240mg kavalactones per day - fixed dose regime of two tablets of kava twice per day</description>
  </arm_group>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Kava (240mg of kavalactones per day)</intervention_name>
    <description>Kava 60 milligrams per tablet = 240mg of kavalactones per day</description>
    <arm_group_label>Kava - standardised 240mg kavalactones</arm_group_label>
    <other_name>Kava</other_name>
    <other_name>Kavalactones</other_name>
    <other_name>Piper methysticum</other_name>
  </intervention>
  <intervention>
    <intervention_type>Dietary Supplement</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        To be considered for inclusion in this study, participants will be required to meet the&#xD;
        following criteria:&#xD;
&#xD;
          -  Aged between 18-70 years&#xD;
&#xD;
          -  Meets the Diagnostic and Statistical Manual (DSM) IV and DSM-V diagnostic criteria for&#xD;
             generalised anxiety disorder (GAD) based on structured interview (Mini International&#xD;
             Neuropsychiatric Interview-Plus 6 [MINI-Plus 6]. Note that while the MINI-Plus 6 uses&#xD;
             the DSM-IV criteria, the same criteria are used in the DSM-V).&#xD;
&#xD;
          -  Presents with anxiety (Hamilton Anxiety Rating Scale ≥ 18) at the time of study entry&#xD;
&#xD;
          -  Fluent in written and spoken English&#xD;
&#xD;
          -  Provides a signed copy of the consent form&#xD;
&#xD;
        Participants are ineligible to enter the trial if they have any of the following&#xD;
        conditions:&#xD;
&#xD;
          -  Primary diagnosis other than GAD&#xD;
&#xD;
          -  Presentation of moderate to severe depressive symptoms (Montgomery-Asberg Rating&#xD;
             Scale: MADRS ≥ 18 at time of study entry or ≥ 24 at any time during study)&#xD;
&#xD;
          -  Presentation of suicidal ideation (≥ 3 on MADRS suicidal thoughts domain at time of&#xD;
             study entry or at any time during study)&#xD;
&#xD;
          -  Current diagnosis of bipolar disorder or schizophrenia on structured interview (MINI&#xD;
             Plus)&#xD;
&#xD;
          -  Current substance/alcohol use disorder on structured interview (MINI Plus) Page 21 of&#xD;
             39 Commercial-in-Confidence&#xD;
&#xD;
          -  Currently taking an antidepressant, mood stabiliser, antipsychotic, anticonvulsant,&#xD;
             warfarin or thyroxin, or current regular use (more than 2 days per week) of a&#xD;
             benzodiazepine or opioid-based analgesic&#xD;
&#xD;
          -  Current use of a psychotropic nutraceutical (e.g. St John's wort)&#xD;
&#xD;
          -  Previous intolerance to kava&#xD;
&#xD;
          -  Three or more failed trials of pharmacotherapy for the current GAD episode&#xD;
&#xD;
          -  Recently commenced psychotherapy (within four weeks of study entry)&#xD;
&#xD;
          -  Known or suspected clinically unstable systemic medical disorder&#xD;
&#xD;
          -  Diagnosed hepato-biliary disease/inflammation&#xD;
&#xD;
          -  Elevated liver enzymes at baseline blood test&#xD;
&#xD;
          -  Pregnancy or breastfeeding, or trying to conceive&#xD;
&#xD;
          -  Not using medically approved contraception (including abstinence) if female and of&#xD;
             childbearing age&#xD;
&#xD;
          -  Unable to participate in all scheduled visits, treatment plan, or other trial&#xD;
             procedures according to the protocol (except for the optional genetic component)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jerome Sarris, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Melbourne and The Melbourne Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Royal Brisbane &amp; Women's Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4006</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Centre for Human Psychopharmacology - Swinburne University</name>
      <address>
        <city>Melbourne</city>
        <state>Victoria</state>
        <zip>3122</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>August 13, 2014</study_first_submitted>
  <study_first_submitted_qc>August 17, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 19, 2014</study_first_posted>
  <last_update_submitted>October 10, 2018</last_update_submitted>
  <last_update_submitted_qc>October 10, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">October 15, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Melbourne</investigator_affiliation>
    <investigator_full_name>Jerome Sarris</investigator_full_name>
    <investigator_title>Dr Jerome Sarris</investigator_title>
  </responsible_party>
  <keyword>Kava</keyword>
  <keyword>Anxiety</keyword>
  <keyword>Generalized Anxiety Disorder</keyword>
  <keyword>Psychiatric</keyword>
  <keyword>Anxiolytic</keyword>
  <keyword>GABA</keyword>
  <keyword>Kavalactones</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anxiety 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/NCT02219880
org study id: 137/14
nct id: NCT02219880
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
The use of Kava in Generalised Anxiety Disorder: an 18-week double-blind, randomised,
      placebo-controlled study.
The primary aim is to confirm the efficacy and safety of Kava compared to placebo in
      Generalized Anxiety Disorder (GAD). Secondary aims of the study are to confirm the
      relationship between specific genetic variations and response to Kava, and to explore the
      effects of Kava on the expression of specific genes.

      Consenting participants will be randomly allocated to take either Kava or placebo over 18
      weeks. They will be assessed at regular interviews throughout the trial and will have four
      blood tests (liver function tests to monitor participant safety, and collection of genetic
      material providing information on neurochemistry). The design of the study is a multi-centre,
      18-week, 2-arm, double-blind randomised clinical trial (RCT) using a standardised
      pharmaceutical-grade water-soluble extract of Kava (240mg of kavalactones per day) versus
      placebo in 210 adults with GAD.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Hamilton Anxiety Rating Scale (HAMA) - change in score
time frame: 18 weeks
description: Reduction of participant's anxiety will be assessed on the HAMA from baseline to week 16 across time used a mixed methods model.
measure: Gamma-aminobutyric acid (GABA) transporter polymorphisms moderating response to study intervention
time frame: 18 weeks
description: Will assess whether response to Kava will be moderated by gamma-aminobutyric acid (GABA) transporter polymorphisms. Specifically, whether rs2601126-T allele or rs2697153-A allele carriers have greater reduction of anxiety
measure: Changes in score to psychometric questionnaire measures
time frame: 18 weeks
description: Depressive symptoms on the Montgomery-Asberg Depression Rating Scale (MADRS), self-rated anxiety on the Beck Anxiety Inventory (BAI), pathological worry on the Penn State Worry Questionnaire (PSWQ), and health-related quality of life on the Short Form Survey-12 (SF-12) will also be significantly improved by Kava over placebo; and
measure: Monoamine and GABA differential gene expression
time frame: 8 weeks
description: Differential gene expression will be assessed from baseline to week 8 from participants in the Melbourne site. This will determine whether Kava increases expression of genes effecting expression of neurochemical e.g. GABA, and monoamines
arm group label: Placebo
arm group type: Placebo Comparator
description: Inert tablets matched for colour, size and consistency to active arm treatment. Both treatment arm tablets will match in appearance, and neither participants nor the trial clinicians will know what they are taking.
arm group label: Kava - standardised 240mg kavalactones
arm group type: Experimental
description: Standardised 240mg kavalactones per day - fixed dose regime of two tablets of kava twice per day
intervention type: Dietary Supplement
intervention name: Kava (240mg of kavalactones per day)
description: Kava 60 milligrams per tablet = 240mg of kavalactones per day
arm group label: Kava - standardised 240mg kavalactones
other name: Kava
other name: Kavalactones
other name: Piper methysticum
intervention type: Dietary Supplement
intervention name: Placebo
description: Inert tablets containing vegetable fibre matched for colour, size and consistency to active arm treatment.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Jerome Sarris, PhD
role: Principal Investigator
affiliation: The University of Melbourne and The Melbourne Clinic
facility: 
facility: 
country: Australia
responsible party type: Principal Investigator
investigator affiliation: University of Melbourne
investigator full name: Jerome Sarris
investigator title: Dr Jerome Sarris
mesh term: Anxiety Disorders