Clinical and Imaging Trial of Uridine for Veterans With Suicidal Ideation

NCT03265964 | Completed Phase 4 Results DMC FDA Drug

• 2 other identifiers: MHBB-012-16F00100075
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Suicidal Ideation

Keywords

Suicidal Ideation; Veteran; Uridine; Neuroimaging

Outcome Measures

Primary Outcomes (3)

• Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS)

  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. Scores range from 0 to 25 with higher scores representing more severe suicidal ideation.

  4 weeks

• Change From Baseline in Beck Scale for Suicide Ideation (BSSI)

  The hypothesis is that 4 weeks of uridine 2000 mg daily will decrease the probability and severity of suicidal ideation measured with the BSSI compared with placebo. The BSSI is a 19 item measure on a 0-2 point scale for a range of 0-38, with higher scores indicating higher suicidal ideation or worse outcomes.

  4 weeks

• Change From Baseline in Brain Gamma-Aminobutyric Acid (GABA)/NAA Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging

  The hypothesis is that Brain Gamma-Aminobutyric Acid (GABA)/NAA levels will show a greater increase after 1 week, in uridine-treated vs. placebo-treated veterans with suicidal ideation. Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) is a safe and non-invasive method for in-vivo measurement of brain chemistry relevant to mental health, including the neurotransmitters, glutamate, glutamine, and GABA.

  1 week

Secondary Outcomes (1)

• Change From Baseline in Brain Total Choline/N-acetylaspartate (NAA) Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging

  1 week

Study Arms (2)

Uridine

ACTIVE COMPARATOR

Subjects randomized to this study arm will receive uridine 2000 mg daily by mouth for 4 weeks

Drug: Uridine

Placebo

PLACEBO COMPARATOR

Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks.

Drug: Placebo

Interventions

Uridine DRUG

Uridine is the active treatment in this clinical trial.

Also known as: Oral Uridine

Uridine

Placebo DRUG

Pill placebo is the inactive treatment comparator in this clinical trial.

Also known as: Oral Pill Placebo

Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Must be able to Provide Informed Consent.
• Must be a Veteran of the U.S. Armed Forces.
• Columbia-Suicide Severity Rating Scale Indicates Current Suicidal Ideation
• Beck Scale for Suicide Ideation Score \> 3 (i.e. "Greater Than or Equal to 4").
• History of \> 1 Suicide Attempt or Hospitalization to Prevent Suicide in Past 12 Months; or Functionally Impairing Suicidal Ideation Not Due to a DSM Axis II Diagnosis, in the Past 12 Months.
• Females and Males Ages 18-55 Inclusive.
• Willing and Able to Identify an Alternative Contact Person, e.g. Family Member, Friend or Neighbor.

You may not qualify if:

• Schizophrenia or Other Psychotic Disorder.
• Active Substance Use Disorder Requiring Stabilization (N.B. Does Not Include Nicotine).
• Unstable Medical Condition(s).
• Pregnancy or Breastfeeding.
• Contraindication to MRI (e.g. Ferrometallic Implant or Claustrophobic Anxiety).
• Concurrent Enrollment in Another Clinical Trial.
• Significant Risk of Protocol Non-Adherence (e.g. resides \> 50 miles from the hospital, and has no automobile or alternate transportation).

Sponsors & Collaborators

• VA Office of Research and Development: lead

Study Sites (1)

VA Salt Lake City Health Care System, Salt Lake City, UT

Salt Lake City, Utah, 84148-0001, United States

Location

Related Publications (11)

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

Related Links

• Methods of treatment of bipolar disorder \[US Patent Application 20110160158 A1\]

MeSH Terms

Conditions

Suicidal Ideation

Interventions

Uridine

Condition Hierarchy (Ancestors)

Suicide; Self-Injurious Behavior; Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Ribonucleosides

Results Point of Contact

• Title: Dr. Douglas Kondo
• Organization: VA Salt Lake City Health Care System, VISN 19 Rocky Mountain MIRECC for Veteran Suicide Prevention

douglas.kondo@va.gov

801-587-1549

Study Officials

• Douglas Gavin Kondo, MD

  VA Salt Lake City Health Care System, Salt Lake City, UT

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 25, 2017
• First Posted: August 29, 2017
• Study Start: April 2, 2018
• Primary Completion: June 30, 2024
• Study Completion: June 30, 2024
• Last Updated: August 15, 2025
• Results First Posted: August 15, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)