<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/NCT03265964</url>
  </required_header>
  <id_info>
    <org_study_id>MHBB-012-16F</org_study_id>
    <secondary_id>00100075</secondary_id>
    <nct_id>NCT03265964</nct_id>
  </id_info>
  <brief_title>Clinical and Imaging Trial of Uridine for Veterans With Suicidal Ideation</brief_title>
  <official_title>Clinical and Imaging Biomarker Trial of Uridine for Veterans With Suicidal Ideation</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <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>
      This is a randomized, double-blind, placebo-controlled study of the investigational drug&#xD;
      uridine as a treatment for suicidal ideation in veterans.&#xD;
&#xD;
      The investigators hypothesize that the administration of a naturally occurring dietary&#xD;
      supplement, uridine, will rapidly reduce suicidal ideation in veterans. The purpose of this&#xD;
      study is to determine whether 4 weeks of uridine supplementation is an effective treatment&#xD;
      for suicidal ideation in veterans, when compared to a group taking a placebo.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Veteran suicides, attempts and suicidal ideation (SI) remain an urgent concern for the&#xD;
      Veterans Health Administration (VHA). Research indicates that approximately half of veteran&#xD;
      suicides take place within 1 month of the decedent's final VHA encounter, with one quarter&#xD;
      occurring within 1 week. This provides a temporal window of opportunity to intervene, and&#xD;
      necessitates development of a rapid-acting treatment for veterans with SI. Uridine shares&#xD;
      similar brain mechanisms and neural effects with ketamin and lithium, treatments commonly&#xD;
      used to reduce suicidal ideation. This study will test the novel intervention uridine as a&#xD;
      rapid-acting oral treatment for veterans with suicidal ideation. The purpose of this study is&#xD;
      to investigate whether uridine can decrease suicidal ideation in veterans when taken daily&#xD;
      for 4 weeks.&#xD;
&#xD;
      In addition to treatment with the investigational drug versus placebo, the study includes a&#xD;
      translational neuroimaging component: magnetic resonance spectroscopy (1H-MRS) brain scans&#xD;
      are performed at baseline, and then repeated following 1 week of treatment with uridine or&#xD;
      placebo. The scans do not use radiation, and are performed on a 3 Tesla MRI system that is&#xD;
      approved for clinical use. The scans allow researchers to measure the concentrations of&#xD;
      several chemicals in the brain that are may be involved in suicidal ideation.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 2, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2023</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>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>Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)</measure>
    <time_frame>4 weeks</time_frame>
    <description>The hypothesis is that 4 weeks of uridine 2000 mg daily will decrease the probability and severity of suicidal ideation measured with the C-SSRS, compared with placebo.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline in Brain GABA Levels, Measured with Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging</measure>
    <time_frame>1 week</time_frame>
    <description>The hypothesis is that brain GABA levels will show a greater increase after 1 week, in uridine-treated vs. placebo-treated veterans with suicidal ideation.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Suicidal Ideation</condition>
  <arm_group>
    <arm_group_label>Uridine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Subjects randomized to this study arm will receive uridine 2000 mg daily by mouth for 4 weeks</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Uridine</intervention_name>
    <description>Uridine is the active treatment in this clinical trial.</description>
    <arm_group_label>Uridine</arm_group_label>
    <other_name>Oral Uridine</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Pill placebo is the inactive treatment comparator in this clinical trial.</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>Oral Pill Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Must be able to Provide Informed Consent.&#xD;
&#xD;
          -  Must be a Veteran of the U.S. Armed Forces.&#xD;
&#xD;
          -  Columbia-Suicide Severity Rating Scale Indicates Current Suicidal Ideation&#xD;
&#xD;
          -  Beck Scale for Suicide Ideation Score &gt; 3 (i.e. &quot;Greater Than or Equal to 4&quot;).&#xD;
&#xD;
          -  History of &gt; 1 Suicide Attempt or Hospitalization to Prevent Suicide in Past 12&#xD;
             Months; or Functionally Impairing Suicidal Ideation Not Due to a DSM Axis II&#xD;
             Diagnosis, in the Past 12 Months.&#xD;
&#xD;
          -  Females and Males Ages 18-55 Inclusive.&#xD;
&#xD;
          -  Willing and Able to Identify an Alternative Contact Person, e.g. Family Member, Friend&#xD;
             or Neighbor.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Schizophrenia or Other Psychotic Disorder.&#xD;
&#xD;
          -  Active Substance Use Disorder Requiring Stabilization (N.B. Does Not Include&#xD;
             Nicotine).&#xD;
&#xD;
          -  Unstable Medical Condition(s).&#xD;
&#xD;
          -  Pregnancy or Breastfeeding.&#xD;
&#xD;
          -  Contraindication to MRI (e.g. Ferrometallic Implant or Claustrophobic Anxiety).&#xD;
&#xD;
          -  Concurrent Enrollment in Another Clinical Trial.&#xD;
&#xD;
          -  Significant Risk of Protocol Non-Adherence (e.g. resides &gt; 50 miles from the hospital,&#xD;
             and has no automobile or alternate transportation).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Douglas Gavin Kondo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>VA Salt Lake City Health Care System, Salt Lake City, UT</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Douglas G Kondo, MD</last_name>
    <phone>(801) 582-1565</phone>
    <phone_ext>2821</phone_ext>
    <email>doug.kondo@hsc.utah.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Danielle Boxer, MS BA</last_name>
    <phone>(801) 587-1549</phone>
    <email>danielle.boxer@utah.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>VA Salt Lake City Health Care System, Salt Lake City, UT</name>
      <address>
        <city>Salt Lake City</city>
        <state>Utah</state>
        <zip>84148-0001</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Douglas G Kondo, MD</last_name>
      <phone>(801) 582-1565</phone>
      <phone_ext>2821</phone_ext>
      <email>doug.kondo@hsc.utah.edu</email>
    </contact>
    <investigator>
      <last_name>Douglas Gavin Kondo, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.google.com/patents/US20110160158</url>
    <description>Methods of treatment of bipolar disorder [US Patent Application 20110160158 A1]</description>
  </link>
  <reference>
    <citation>Kondo DG, Sung YH, Hellem TL, Delmastro KK, Jeong EK, Kim N, Shi X, Renshaw PF. Open-label uridine for treatment of depressed adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2011 Apr;21(2):171-5. doi: 10.1089/cap.2010.0054. Epub 2011 Apr 12.</citation>
    <PMID>21486171</PMID>
  </reference>
  <reference>
    <citation>Agarwal N, Sung YH, Jensen JE, daCunha G, Harper D, Olson D, Renshaw PF. Short-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T. Bipolar Disord. 2010 Dec;12(8):825-33. doi: 10.1111/j.1399-5618.2010.00884.x.</citation>
    <PMID>21176029</PMID>
  </reference>
  <reference>
    <citation>Jensen JE, Daniels M, Haws C, Bolo NR, Lyoo IK, Yoon SJ, Cohen BM, Stoll AL, Rusche JR, Renshaw PF. Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients. Exp Clin Psychopharmacol. 2008 Jun;16(3):199-206. doi: 10.1037/1064-1297.16.3.199.</citation>
    <PMID>18540779</PMID>
  </reference>
  <reference>
    <citation>Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005 Feb 15;57(4):343-50. doi: 10.1016/j.biopsych.2004.11.038.</citation>
    <PMID>15705349</PMID>
  </reference>
  <reference>
    <citation>Yoon SJ, Lyoo IK, Kim HJ, Kim TS, Sung YH, Kim N, Lukas SE, Renshaw PF. Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5'-diphosphate choline: a longitudinal proton magnetic resonance spectroscopy study. Neuropsychopharmacology. 2010 Apr;35(5):1165-73. doi: 10.1038/npp.2009.221. Epub 2009 Dec 30.</citation>
    <PMID>20043005</PMID>
  </reference>
  <reference>
    <citation>Wurtman RJ, Cansev M, Ulus IH. Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides. J Nutr Health Aging. 2009 Mar;13(3):189-97. doi: 10.1007/s12603-009-0056-3.</citation>
    <PMID>19262950</PMID>
  </reference>
  <reference>
    <citation>Liu P, Wu C, Song W, Yu L, Yang X, Xiang R, Wang F, Yang J. Uridine decreases morphine-induced behavioral sensitization by decreasing dorsal striatal dopamine release possibly via agonistic effects at GABAA receptors. Eur Neuropsychopharmacol. 2014 Sep;24(9):1557-66. doi: 10.1016/j.euroneuro.2014.06.010. Epub 2014 Jun 28.</citation>
    <PMID>25088943</PMID>
  </reference>
  <reference>
    <citation>Price GD, Robertson SJ, Edwards FA. Long-term potentiation of glutamatergic synaptic transmission induced by activation of presynaptic P2Y receptors in the rat medial habenula nucleus. Eur J Neurosci. 2003 Feb;17(4):844-50. doi: 10.1046/j.1460-9568.2003.02501.x.</citation>
    <PMID>12603274</PMID>
  </reference>
  <reference>
    <citation>Wirkner K, Gunther A, Weber M, Guzman SJ, Krause T, Fuchs J, Koles L, Norenberg W, Illes P. Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation. Cereb Cortex. 2007 Mar;17(3):621-31. doi: 10.1093/cercor/bhk012. Epub 2006 Apr 28.</citation>
    <PMID>16648456</PMID>
  </reference>
  <reference>
    <citation>Saydoff JA, Garcia RA, Browne SE, Liu L, Sheng J, Brenneman D, Hu Z, Cardin S, Gonzalez A, von Borstel RW, Gregorio J, Burr H, Beal MF. Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse models of Huntington's disease. Neurobiol Dis. 2006 Dec;24(3):455-65. doi: 10.1016/j.nbd.2006.08.011. Epub 2006 Sep 29.</citation>
    <PMID>17011205</PMID>
  </reference>
  <reference>
    <citation>Tochigi M, Iwamoto K, Bundo M, Sasaki T, Kato N, Kato T. Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains. Neurosci Res. 2008 Feb;60(2):184-91. doi: 10.1016/j.neures.2007.10.010. Epub 2007 Nov 6.</citation>
    <PMID>18068248</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>August 25, 2017</study_first_submitted>
  <study_first_submitted_qc>August 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 29, 2017</study_first_posted>
  <last_update_submitted>March 22, 2023</last_update_submitted>
  <last_update_submitted_qc>March 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Suicidal Ideation</keyword>
  <keyword>Veteran</keyword>
  <keyword>Uridine</keyword>
  <keyword>Neuroimaging</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Suicidal Ideation</mesh_term>
  </condition_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/NCT03265964
org study id: MHBB-012-16F
secondary id: 00100075
nct id: NCT03265964
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a randomized, double-blind, placebo-controlled study of the investigational drug
      uridine as a treatment for suicidal ideation in veterans.

      The investigators hypothesize that the administration of a naturally occurring dietary
      supplement, uridine, will rapidly reduce suicidal ideation in veterans. The purpose of this
      study is to determine whether 4 weeks of uridine supplementation is an effective treatment
      for suicidal ideation in veterans, when compared to a group taking a placebo.
Veteran suicides, attempts and suicidal ideation (SI) remain an urgent concern for the
      Veterans Health Administration (VHA). Research indicates that approximately half of veteran
      suicides take place within 1 month of the decedent's final VHA encounter, with one quarter
      occurring within 1 week. This provides a temporal window of opportunity to intervene, and
      necessitates development of a rapid-acting treatment for veterans with SI. Uridine shares
      similar brain mechanisms and neural effects with ketamin and lithium, treatments commonly
      used to reduce suicidal ideation. This study will test the novel intervention uridine as a
      rapid-acting oral treatment for veterans with suicidal ideation. The purpose of this study is
      to investigate whether uridine can decrease suicidal ideation in veterans when taken daily
      for 4 weeks.

      In addition to treatment with the investigational drug versus placebo, the study includes a
      translational neuroimaging component: magnetic resonance spectroscopy (1H-MRS) brain scans
      are performed at baseline, and then repeated following 1 week of treatment with uridine or
      placebo. The scans do not use radiation, and are performed on a 3 Tesla MRI system that is
      approved for clinical use. The scans allow researchers to measure the concentrations of
      several chemicals in the brain that are may be involved in suicidal ideation.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change from Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)
time frame: 4 weeks
description: The hypothesis is that 4 weeks of uridine 2000 mg daily will decrease the probability and severity of suicidal ideation measured with the C-SSRS, compared with placebo.
measure: Change from Baseline in Brain GABA Levels, Measured with Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging
time frame: 1 week
description: The hypothesis is that brain GABA levels will show a greater increase after 1 week, in uridine-treated vs. placebo-treated veterans with suicidal ideation.
arm group label: Uridine
arm group type: Active Comparator
description: Subjects randomized to this study arm will receive uridine 2000 mg daily by mouth for 4 weeks
arm group label: Placebo
arm group type: Placebo Comparator
description: Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks.
intervention type: Drug
intervention name: Uridine
description: Uridine is the active treatment in this clinical trial.
arm group label: Uridine
other name: Oral Uridine
intervention type: Drug
intervention name: Placebo
description: Pill placebo is the inactive treatment comparator in this clinical trial.
arm group label: Placebo
other name: Oral Pill Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Douglas Gavin Kondo, MD
role: Principal Investigator
affiliation: VA Salt Lake City Health Care System, Salt Lake City, UT
last name: Douglas G Kondo, MD
phone: (801) 582-1565
phone ext: 2821
email: doug.kondo@hsc.utah.edu
last name: Danielle Boxer, MS BA
phone: (801) 587-1549
email: danielle.boxer@utah.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: https://www.google.com/patents/US20110160158
description: Methods of treatment of bipolar disorder [US Patent Application 20110160158 A1]
citation: Kondo DG, Sung YH, Hellem TL, Delmastro KK, Jeong EK, Kim N, Shi X, Renshaw PF. Open-label uridine for treatment of depressed adolescents with bipolar disorder. J Child Adolesc Psychopharmacol. 2011 Apr;21(2):171-5. doi: 10.1089/cap.2010.0054. Epub 2011 Apr 12.
PMID: 21486171
citation: Agarwal N, Sung YH, Jensen JE, daCunha G, Harper D, Olson D, Renshaw PF. Short-term administration of uridine increases brain membrane phospholipid precursors in healthy adults: a 31-phosphorus magnetic resonance spectroscopy study at 4T. Bipolar Disord. 2010 Dec;12(8):825-33. doi: 10.1111/j.1399-5618.2010.00884.x.
PMID: 21176029
citation: Jensen JE, Daniels M, Haws C, Bolo NR, Lyoo IK, Yoon SJ, Cohen BM, Stoll AL, Rusche JR, Renshaw PF. Triacetyluridine (TAU) decreases depressive symptoms and increases brain pH in bipolar patients. Exp Clin Psychopharmacol. 2008 Jun;16(3):199-206. doi: 10.1037/1064-1297.16.3.199.
PMID: 18540779
citation: Carlezon WA Jr, Mague SD, Parow AM, Stoll AL, Cohen BM, Renshaw PF. Antidepressant-like effects of uridine and omega-3 fatty acids are potentiated by combined treatment in rats. Biol Psychiatry. 2005 Feb 15;57(4):343-50. doi: 10.1016/j.biopsych.2004.11.038.
PMID: 15705349
citation: Yoon SJ, Lyoo IK, Kim HJ, Kim TS, Sung YH, Kim N, Lukas SE, Renshaw PF. Neurochemical alterations in methamphetamine-dependent patients treated with cytidine-5'-diphosphate choline: a longitudinal proton magnetic resonance spectroscopy study. Neuropsychopharmacology. 2010 Apr;35(5):1165-73. doi: 10.1038/npp.2009.221. Epub 2009 Dec 30.
PMID: 20043005
citation: Wurtman RJ, Cansev M, Ulus IH. Synapse formation is enhanced by oral administration of uridine and DHA, the circulating precursors of brain phosphatides. J Nutr Health Aging. 2009 Mar;13(3):189-97. doi: 10.1007/s12603-009-0056-3.
PMID: 19262950
citation: Liu P, Wu C, Song W, Yu L, Yang X, Xiang R, Wang F, Yang J. Uridine decreases morphine-induced behavioral sensitization by decreasing dorsal striatal dopamine release possibly via agonistic effects at GABAA receptors. Eur Neuropsychopharmacol. 2014 Sep;24(9):1557-66. doi: 10.1016/j.euroneuro.2014.06.010. Epub 2014 Jun 28.
PMID: 25088943
citation: Price GD, Robertson SJ, Edwards FA. Long-term potentiation of glutamatergic synaptic transmission induced by activation of presynaptic P2Y receptors in the rat medial habenula nucleus. Eur J Neurosci. 2003 Feb;17(4):844-50. doi: 10.1046/j.1460-9568.2003.02501.x.
PMID: 12603274
citation: Wirkner K, Gunther A, Weber M, Guzman SJ, Krause T, Fuchs J, Koles L, Norenberg W, Illes P. Modulation of NMDA receptor current in layer V pyramidal neurons of the rat prefrontal cortex by P2Y receptor activation. Cereb Cortex. 2007 Mar;17(3):621-31. doi: 10.1093/cercor/bhk012. Epub 2006 Apr 28.
PMID: 16648456
citation: Saydoff JA, Garcia RA, Browne SE, Liu L, Sheng J, Brenneman D, Hu Z, Cardin S, Gonzalez A, von Borstel RW, Gregorio J, Burr H, Beal MF. Oral uridine pro-drug PN401 is neuroprotective in the R6/2 and N171-82Q mouse models of Huntington's disease. Neurobiol Dis. 2006 Dec;24(3):455-65. doi: 10.1016/j.nbd.2006.08.011. Epub 2006 Sep 29.
PMID: 17011205
citation: Tochigi M, Iwamoto K, Bundo M, Sasaki T, Kato N, Kato T. Gene expression profiling of major depression and suicide in the prefrontal cortex of postmortem brains. Neurosci Res. 2008 Feb;60(2):184-91. doi: 10.1016/j.neures.2007.10.010. Epub 2007 Nov 6.
PMID: 18068248
responsible party type: Sponsor
mesh term: Suicidal Ideation
sharing ipd: No