<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/NCT03013400</url>
  </required_header>
  <id_info>
    <org_study_id>172518</org_study_id>
    <secondary_id>2015-000323-86</secondary_id>
    <nct_id>NCT03013400</nct_id>
  </id_info>
  <brief_title>Ebselen as an add-on Treatment in Hypo/Mania</brief_title>
  <official_title>A Randomised, Parallel Group, Double Blind, Placebo Controlled, Add on Clinical Trial to Investigate Whether the Lithium Mimetic, Ebselen, Can Reduce Symptoms of Hypomania and Mania in Bipolar Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Oxford</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Stanley Medical Research Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Sound Pharmaceuticals, Incorporated</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>University of Oxford</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study evaluates the effect of a 'lithium like' drug called ebselen (SP-1005) versus&#xD;
      placebo as an 'add on' treatment to help stabilise hypo/manic symptoms in bipolar disorder.&#xD;
      Half of the participants will receive ebselen and the other half placebo. The trial, will&#xD;
      last a total of four weeks.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Ebselen, a new drug for mania&#xD;
&#xD;
      Bipolar disorder, formerly known as manic depression, is a condition that affects mood, which&#xD;
      can swing from one extreme to another.&#xD;
&#xD;
      Typically, there will be periods of:&#xD;
&#xD;
        -  Depression - very low mood and energy levels&#xD;
&#xD;
        -  Mania or hypomania (less severe) - very high mood and overactive energy levels&#xD;
&#xD;
      A drug called lithium, used to stabilise mood, is an important treatment for bipolar disorder&#xD;
      but has a number of problematic side effects, is not well tolerated by patients and requires&#xD;
      careful monitoring. To replace lithium with other, safer medicines would have clear&#xD;
      advantages. The investigators are interested in an antioxidant medicine(substance that may&#xD;
      prevent or delay cell damage) called ebselen which has been shown to work in a similar way as&#xD;
      lithium and the investigators are investigating whether it might help improve recovery from&#xD;
      manic episodes.&#xD;
&#xD;
      The present study aims to see whether ebselen, used as an 'add-on' treatment can help&#xD;
      stabilise mood in patients experiencing high mood (hypo/mania). Sixty patients experiencing&#xD;
      hypo/mania will be given in a randomised order (similar to tossing a coin) either ebselen or&#xD;
      placebo (dummy) in addition to their usual medication for three weeks after which the add-on&#xD;
      treatment will be stopped. A final follow up visit will take place one week after the study&#xD;
      medication has been stopped. Participants can be in or outpatients and mood will be monitored&#xD;
      with questionnaires and interviews. Activity will also be monitored with the use of an&#xD;
      actiwatch (similar to a wrist watch) which will be worn continuously throughout the study. A&#xD;
      single blood sample will be optional and occur after the first week of treatment to check&#xD;
      plasma levels of ebselen and inflammatory markers. A positive outcome in this trial will be&#xD;
      followed by longer term studies of ebselen in bipolar disorder.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Actual">July 9, 2019</completion_date>
  <primary_completion_date type="Actual">July 9, 2019</primary_completion_date>
  <phase>Phase 2</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Young Mania Rating Scale (YMRS)</measure>
    <time_frame>Change between groups, every week, up to 4 weeks</time_frame>
    <description>Difference in the 11 item clinician-rated YMRS between groups.Total score 0-60.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale</measure>
    <time_frame>Change between groups, every week, up to 4 weeks</time_frame>
    <description>Improvement due to treatment between groups. Very much improved to very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Altman Self Rating Mania Scale (ASRM)</measure>
    <time_frame>Change between groups, 3 x weekly, up to 4 weeks</time_frame>
    <description>Difference in the 5 item self-rated ASRM between groups.Total score 0-20.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Hamilton Rating Scale for Depression (HAM-D)</measure>
    <time_frame>Change between groups, every week, up to 4 weeks</time_frame>
    <description>Difference in the 17 item Clinician-rated HAM-D between groups. Total score 0-52.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Quick Inventory of Depressive Symptomology-Self Rating 16 (QIDS-SR-16)</measure>
    <time_frame>Change between groups, 3 x weekly, up to 4 weeks</time_frame>
    <description>Difference in the 16 item self-rated QIDS-SR-16 between groups. Total score 0-42.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Actigraphy</measure>
    <time_frame>Change in activity between groups, each 24 hours, up to 4 weeks</time_frame>
    <description>To compare the effect of ebselen versus placebo on motor behaviour and the sleep-wake cycle</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Leeds Sleep Evaluation Questionnaire (LSEQ)</measure>
    <time_frame>Change between groups, every week, up to 4 weeks</time_frame>
    <description>Difference in the 4 self-rated sleep domains (10 visual analogue scales) between groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Levels of markers of inflammation in Plasma sample</measure>
    <time_frame>Once at week 1 visit</time_frame>
    <description>To compare the effect of ebselen, versus placebo, on markers of inflammation including C-Reactive Protein and antibodies to common infectious agents such as human herpesviruses and Toxoplasma gondii</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Ebselen levels in Plasma sample</measure>
    <time_frame>Once at week 1 visit</time_frame>
    <description>To assess ebselen levels in plasma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse Events reported</measure>
    <time_frame>Every week, up to 4 weeks</time_frame>
    <description>Self-rated Side Effects Questionnaire</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Concomitant medication recorded</measure>
    <time_frame>Change between groups, every week, up to 4 weeks</time_frame>
    <description>To assess the overall use of concomitant medication during the trial period</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Compliance assessment</measure>
    <time_frame>Change between groups, every week, up to 3 weeks</time_frame>
    <description>capsule count and records checked</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Researcher and participant blinding questionnaire to determine treatment concealment</measure>
    <time_frame>Once, at week 4</time_frame>
    <description>Researcher and participant blinding questionnaire</description>
  </other_outcome>
  <other_outcome>
    <measure>Participant and Researcher Randomisation Guess Visual Analogue Scale (VAS)</measure>
    <time_frame>Once, at week 4</time_frame>
    <description>To assess whether researchers and participants could guess the assigned randomised arm</description>
  </other_outcome>
  <other_outcome>
    <measure>Public Participant Involvement (PPI) feedback questionnaire</measure>
    <time_frame>Once, at week 4</time_frame>
    <description>PPI questionnaire</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Bipolar Disorder</condition>
  <condition>Bipolar Disorder, Manic</condition>
  <arm_group>
    <arm_group_label>Ebselen</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Three Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Three Placebo capsules each containing 200mg taken orally twice a day for 3 weeks</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ebselen</intervention_name>
    <description>Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.</description>
    <arm_group_label>Ebselen</arm_group_label>
    <other_name>SPI-1005</other_name>
    <other_name>PZ-51</other_name>
    <other_name>Ebselene</other_name>
    <other_name>Ebselenum</other_name>
    <other_name>Ebseleno</other_name>
    <other_name>Harmokisane</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>Placebo is identical in appearance to the ebselen capsules</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Dummy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participant is willing and able to give informed consent for participation in the&#xD;
             trial.&#xD;
&#xD;
          -  Male or Female, aged 18-70 years&#xD;
&#xD;
          -  Diagnosed with bipolar disorder, screened using the Structured Clinical Interview for&#xD;
             DSM-5 (SCID) to meet Diagnostic and Statistical Manual of Mental Disorders (DSM-5)&#xD;
             criteria for Manic or Hypomanic Episode.&#xD;
&#xD;
          -  Female participants of child bearing potential and male participants whose partner is&#xD;
             of child bearing potential must be willing to ensure that they or their partner use&#xD;
             effective contraception during the trial&#xD;
&#xD;
          -  In the Investigator's opinion, is able and willing to comply with all trial&#xD;
             requirements.&#xD;
&#xD;
          -  Willing to allow clinical care team (including General Practitioner (GP)) to be made&#xD;
             aware of trial participation.&#xD;
&#xD;
          -  The Clinical team treating the patient are in agreement.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Female participant who is pregnant, lactating or planning pregnancy during the course&#xD;
             of the trial.&#xD;
&#xD;
          -  Known significant renal or hepatic impairment.&#xD;
&#xD;
          -  Scheduled elective surgery or other procedures requiring general anaesthesia during&#xD;
             the trial.&#xD;
&#xD;
          -  Any other significant disease or disorder which, in the opinion of the Investigator,&#xD;
             may either put the participants at risk because of participation in the trial, or may&#xD;
             influence the result of the trial, or the participant's ability to participate in the&#xD;
             trial.&#xD;
&#xD;
          -  Participants who have participated in another research trial involving an&#xD;
             investigational product in the past 12 weeks.&#xD;
&#xD;
          -  Clinically significant illicit substance or alcohol misuse where dependence criteria&#xD;
             are satisfied.&#xD;
&#xD;
          -  Taking lithium.&#xD;
&#xD;
          -  Previous randomisation to this trial.&#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>Philip J Cowen, MBBS, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Oxford</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Neurosciences Building, Dept. Psychiatry, Warneford Hospital</name>
      <address>
        <city>Oxford</city>
        <state>Oxfordshire</state>
        <zip>OX37JX</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <reference>
    <citation>Masaki C, Sharpley AL, Cooper CM, Godlewska BR, Singh N, Vasudevan SR, Harmer CJ, Churchill GC, Sharp T, Rogers RD, Cowen PJ. Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing. Psychopharmacology (Berl). 2016 Jul;233(14):2655-61. doi: 10.1007/s00213-016-4319-5. Epub 2016 Jun 2.</citation>
    <PMID>27256357</PMID>
  </reference>
  <reference>
    <citation>Masaki C, Sharpley AL, Godlewska BR, Berrington A, Hashimoto T, Singh N, Vasudevan SR, Emir UE, Churchill GC, Cowen PJ. Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla. Psychopharmacology (Berl). 2016 Mar;233(6):1097-104. doi: 10.1007/s00213-015-4189-2. Epub 2016 Jan 12.</citation>
    <PMID>26758281</PMID>
  </reference>
  <reference>
    <citation>Singh N, Sharpley AL, Emir UE, Masaki C, Herzallah MM, Gluck MA, Sharp T, Harmer CJ, Vasudevan SR, Cowen PJ, Churchill GC. Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans. Neuropsychopharmacology. 2016 Jun;41(7):1768-78. doi: 10.1038/npp.2015.343. Epub 2015 Nov 23.</citation>
    <PMID>26593266</PMID>
  </reference>
  <reference>
    <citation>Singh N, Halliday AC, Thomas JM, Kuznetsova OV, Baldwin R, Woon EC, Aley PK, Antoniadou I, Sharp T, Vasudevan SR, Churchill GC. A safe lithium mimetic for bipolar disorder. Nat Commun. 2013;4:1332. doi: 10.1038/ncomms2320.</citation>
    <PMID>23299882</PMID>
  </reference>
  <verification_date>November 2017</verification_date>
  <study_first_submitted>December 9, 2016</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>September 5, 2019</last_update_submitted>
  <last_update_submitted_qc>September 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bipolar Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ebselen</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03013400
org study id: 172518
secondary id: 2015-000323-86
nct id: NCT03013400
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study evaluates the effect of a 'lithium like' drug called ebselen (SP-1005) versus
      placebo as an 'add on' treatment to help stabilise hypo/manic symptoms in bipolar disorder.
      Half of the participants will receive ebselen and the other half placebo. The trial, will
      last a total of four weeks.
Ebselen, a new drug for mania

      Bipolar disorder, formerly known as manic depression, is a condition that affects mood, which
      can swing from one extreme to another.

      Typically, there will be periods of:

        -  Depression - very low mood and energy levels

        -  Mania or hypomania (less severe) - very high mood and overactive energy levels

      A drug called lithium, used to stabilise mood, is an important treatment for bipolar disorder
      but has a number of problematic side effects, is not well tolerated by patients and requires
      careful monitoring. To replace lithium with other, safer medicines would have clear
      advantages. The investigators are interested in an antioxidant medicine(substance that may
      prevent or delay cell damage) called ebselen which has been shown to work in a similar way as
      lithium and the investigators are investigating whether it might help improve recovery from
      manic episodes.

      The present study aims to see whether ebselen, used as an 'add-on' treatment can help
      stabilise mood in patients experiencing high mood (hypo/mania). Sixty patients experiencing
      hypo/mania will be given in a randomised order (similar to tossing a coin) either ebselen or
      placebo (dummy) in addition to their usual medication for three weeks after which the add-on
      treatment will be stopped. A final follow up visit will take place one week after the study
      medication has been stopped. Participants can be in or outpatients and mood will be monitored
      with questionnaires and interviews. Activity will also be monitored with the use of an
      actiwatch (similar to a wrist watch) which will be worn continuously throughout the study. A
      single blood sample will be optional and occur after the first week of treatment to check
      plasma levels of ebselen and inflammatory markers. A positive outcome in this trial will be
      followed by longer term studies of ebselen in bipolar disorder.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in Young Mania Rating Scale (YMRS)
time frame: Change between groups, every week, up to 4 weeks
description: Difference in the 11 item clinician-rated YMRS between groups.Total score 0-60.
measure: Change in Clinical Global Impressions Bipolar (CGI-BP) mania scale
time frame: Change between groups, every week, up to 4 weeks
description: Improvement due to treatment between groups. Very much improved to very much worse.
measure: Change in Altman Self Rating Mania Scale (ASRM)
time frame: Change between groups, 3 x weekly, up to 4 weeks
description: Difference in the 5 item self-rated ASRM between groups.Total score 0-20.
measure: Change in Hamilton Rating Scale for Depression (HAM-D)
time frame: Change between groups, every week, up to 4 weeks
description: Difference in the 17 item Clinician-rated HAM-D between groups. Total score 0-52.
measure: Change in Quick Inventory of Depressive Symptomology-Self Rating 16 (QIDS-SR-16)
time frame: Change between groups, 3 x weekly, up to 4 weeks
description: Difference in the 16 item self-rated QIDS-SR-16 between groups. Total score 0-42.
measure: Change in Actigraphy
time frame: Change in activity between groups, each 24 hours, up to 4 weeks
description: To compare the effect of ebselen versus placebo on motor behaviour and the sleep-wake cycle
measure: Change in Leeds Sleep Evaluation Questionnaire (LSEQ)
time frame: Change between groups, every week, up to 4 weeks
description: Difference in the 4 self-rated sleep domains (10 visual analogue scales) between groups.
measure: Levels of markers of inflammation in Plasma sample
time frame: Once at week 1 visit
description: To compare the effect of ebselen, versus placebo, on markers of inflammation including C-Reactive Protein and antibodies to common infectious agents such as human herpesviruses and Toxoplasma gondii
measure: Ebselen levels in Plasma sample
time frame: Once at week 1 visit
description: To assess ebselen levels in plasma
measure: Adverse Events reported
time frame: Every week, up to 4 weeks
description: Self-rated Side Effects Questionnaire
measure: Change in Concomitant medication recorded
time frame: Change between groups, every week, up to 4 weeks
description: To assess the overall use of concomitant medication during the trial period
measure: Compliance assessment
time frame: Change between groups, every week, up to 3 weeks
description: capsule count and records checked
measure: Researcher and participant blinding questionnaire to determine treatment concealment
time frame: Once, at week 4
description: Researcher and participant blinding questionnaire
measure: Participant and Researcher Randomisation Guess Visual Analogue Scale (VAS)
time frame: Once, at week 4
description: To assess whether researchers and participants could guess the assigned randomised arm
measure: Public Participant Involvement (PPI) feedback questionnaire
time frame: Once, at week 4
description: PPI questionnaire
arm group label: Ebselen
arm group type: Active Comparator
description: Three Ebselen capsules each containing 200mg taken orally twice a day for 3 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Three Placebo capsules each containing 200mg taken orally twice a day for 3 weeks
intervention type: Drug
intervention name: Ebselen
description: Ebselen is an opaque capsule containing 200 mg of ebselen is a selenium-based GPx mimic and IMPase inhibitor.
arm group label: Ebselen
other name: SPI-1005
other name: PZ-51
other name: Ebselene
other name: Ebselenum
other name: Ebseleno
other name: Harmokisane
intervention type: Drug
intervention name: Placebo oral capsule
description: Placebo is identical in appearance to the ebselen capsules
arm group label: Placebo
other name: Dummy
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Philip J Cowen, MBBS, MD
role: Principal Investigator
affiliation: University of Oxford
facility: 
country: United Kingdom
citation: Masaki C, Sharpley AL, Cooper CM, Godlewska BR, Singh N, Vasudevan SR, Harmer CJ, Churchill GC, Sharp T, Rogers RD, Cowen PJ. Effects of the potential lithium-mimetic, ebselen, on impulsivity and emotional processing. Psychopharmacology (Berl). 2016 Jul;233(14):2655-61. doi: 10.1007/s00213-016-4319-5. Epub 2016 Jun 2.
PMID: 27256357
citation: Masaki C, Sharpley AL, Godlewska BR, Berrington A, Hashimoto T, Singh N, Vasudevan SR, Emir UE, Churchill GC, Cowen PJ. Effects of the potential lithium-mimetic, ebselen, on brain neurochemistry: a magnetic resonance spectroscopy study at 7 tesla. Psychopharmacology (Berl). 2016 Mar;233(6):1097-104. doi: 10.1007/s00213-015-4189-2. Epub 2016 Jan 12.
PMID: 26758281
citation: Singh N, Sharpley AL, Emir UE, Masaki C, Herzallah MM, Gluck MA, Sharp T, Harmer CJ, Vasudevan SR, Cowen PJ, Churchill GC. Effect of the Putative Lithium Mimetic Ebselen on Brain Myo-Inositol, Sleep, and Emotional Processing in Humans. Neuropsychopharmacology. 2016 Jun;41(7):1768-78. doi: 10.1038/npp.2015.343. Epub 2015 Nov 23.
PMID: 26593266
citation: Singh N, Halliday AC, Thomas JM, Kuznetsova OV, Baldwin R, Woon EC, Aley PK, Antoniadou I, Sharp T, Vasudevan SR, Churchill GC. A safe lithium mimetic for bipolar disorder. Nat Commun. 2013;4:1332. doi: 10.1038/ncomms2320.
PMID: 23299882
responsible party type: Sponsor
mesh term: Bipolar Disorder
mesh term: Ebselen
sharing ipd: Undecided