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| ID | Type | Description | Link |
|---|---|---|---|
| 00100075 | Other Identifier | Salt Lake City VAMC |
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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 ketamine 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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Uridine | Active Comparator | Subjects randomized to this study arm will receive uridine 2000 mg daily by mouth for 4 weeks |
|
| Placebo | Placebo Comparator | Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Uridine | Drug | Uridine is the active treatment in this clinical trial. |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Change From Baseline in Brain Total Choline/N-acetylaspartate (NAA) Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | 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 neurometabolites, choline and N-acetylaspartate. | 1 week |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Douglas Gavin Kondo, MD | VA Salt Lake City Health Care System, Salt Lake City, UT | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Salt Lake City Health Care System, Salt Lake City, UT | Salt Lake City | Utah | 84148-0001 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21486171 | Background | 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. | |
| 21176029 | 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. |
| Label | URL |
|---|---|
| Methods of treatment of bipolar disorder \[US Patent Application 20110160158 A1\] | View source |
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| ID | Title | Description |
|---|---|---|
| FG000 | Uridine | Subjects randomized to this study arm will receive uridine 2000 mg daily by mouth for 4 weeks Uridine: Uridine is the active treatment in this clinical trial. |
| FG001 | Placebo | Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks. Placebo: Pill placebo is the inactive treatment comparator in this clinical trial. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Uridine | Subjects randomized to this study arm will receive uridine 2000 mg daily by mouth for 4 weeks Uridine: Uridine is the active treatment in this clinical trial. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | Participants who were non-adherent to the study protocol or had medication changes throughout the clinical trial were removed from this analysis. | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
4 weeks
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Uridine | Subjects randomized to this study arm will receive uridine 2000 mg daily by mouth for 4 weeks Uridine: Uridine is the active treatment in this clinical trial. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Suicidal Ideation/Behavior | Psychiatric disorders | Systematic Assessment | The participant completed treatment but missed the final visit. Staff learned they were hospitalized for suicidal ideation, opioid withdrawal, and methamphetamine-induced psychosis. Their history included 7 attempts, 2 interrupted, and 5 aborted. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Abdominal cramp, Nausea, Indigestion, Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Douglas Kondo | VA Salt Lake City Health Care System, VISN 19 Rocky Mountain MIRECC for Veteran Suicide Prevention | 801-587-1549 | douglas.kondo@va.gov |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 12, 2022 | Jun 18, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D059020 | Suicidal Ideation |
| ID | Term |
|---|---|
| D013405 | Suicide |
| D016728 | Self-Injurious Behavior |
| D001526 | Behavioral Symptoms |
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D014529 | Uridine |
| ID | Term |
|---|---|
| D011741 | Pyrimidine Nucleosides |
| D011743 | Pyrimidines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| Placebo | Drug | Pill placebo is the inactive treatment comparator in this clinical trial. |
|
|
| 18540779 | 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. |
| 15705349 | 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. |
| 20043005 | 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. |
| 19262950 | 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. |
| 25088943 | 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. |
| 12603274 | 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. |
| 16648456 | 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. |
| 17011205 | 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. |
| 18068248 | 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. |
Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks.
Placebo: Pill placebo is the inactive treatment comparator in this clinical trial.
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks. Placebo: Pill placebo is the inactive treatment comparator in this clinical trial. |
|
|
| Primary | 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. | Participants who were non-adherent to the study protocol or had medication changes throughout the clinical trial were removed from this analysis. | Posted | Mean | Standard Deviation | score on a scale | 4 weeks |
|
|
|
| Primary | 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. | Statistical outliers and motion-corrupted neuroimaging data were removed from this analysis. | Posted | Mean | Standard Deviation | ratio of GABA/NAA | 1 week |
|
|
|
| Secondary | Change From Baseline in Brain Total Choline/N-acetylaspartate (NAA) Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | 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 neurometabolites, choline and N-acetylaspartate. | Statistical outliers and motion-corrupted neuroimaging data were removed from this analysis. | Posted | Mean | Standard Deviation | ratio of tCho/NAA | 1 week |
|
|
|
| 0 |
| 37 |
| 0 |
| 37 |
| 21 |
| 37 |
| EG001 | Placebo | Subjects randomized to this arm of the study will receive placebo 2000 mg daily by mouth for 4 weeks. Placebo: Pill placebo is the inactive treatment comparator in this clinical trial. | 0 | 38 | 1 | 38 | 27 | 38 |
|
| Headache, lightheadedness | Nervous system disorders | Systematic Assessment |
|
| Psychiatric | Psychiatric disorders | Systematic Assessment |
|
| Respiratory | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
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| D009705 | Nucleosides |
| D009706 | Nucleic Acids, Nucleotides, and Nucleosides |
| D012263 | Ribonucleosides |