Suicidal Ideation
Conditions
Keywords
Suicidal Ideation, Veteran, Uridine, Neuroimaging
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.
Detailed description
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.
Interventions
DRUGUridine
Uridine is the active treatment in this clinical trial.
DRUGPlacebo
Pill placebo is the inactive treatment comparator in this clinical trial.
Sponsors
VA Office of Research and Development
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
* 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.
Exclusion criteria
* 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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | 4 weeks | 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. |
| Change From Baseline in Beck Scale for Suicide Ideation (BSSI) | 4 weeks | 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. |
| Change From Baseline in Brain Gamma-Aminobutyric Acid (GABA)/NAA Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | 1 week | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Brain Total Choline/N-acetylaspartate (NAA) Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | 1 week | 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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. | 37 |
| 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. | 38 |
| Total | 75 |
Baseline characteristics
| Characteristic | Uridine | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 37 Participants | 38 Participants | 75 Participants |
| Age, Continuous | 40.89 years STANDARD_DEVIATION 8.33 | 37.65 years STANDARD_DEVIATION 7.14 | 39.29 years STANDARD_DEVIATION 7.88 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 7 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 34 Participants | 31 Participants | 65 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment United States | 37 Participants | 38 Participants | 75 Participants |
| Sex: Female, Male Female | 6 Participants | 8 Participants | 14 Participants |
| Sex: Female, Male Male | 31 Participants | 30 Participants | 61 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 37 | 0 / 38 |
| other Total, other adverse events | 21 / 37 | 27 / 38 |
| serious Total, serious adverse events | 0 / 37 | 1 / 38 |
Outcome results
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.
Time frame: 4 weeks
Population: Participants who were non-adherent to the study protocol or had medication changes throughout the clinical trial were removed from this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Uridine | Change From Baseline in Beck Scale for Suicide Ideation (BSSI) | Baseline: Week 0 | 14.52 score on a scale | Standard Deviation 4.26 |
| Uridine | Change From Baseline in Beck Scale for Suicide Ideation (BSSI) | End of Treatment: Week 4 | 6.35 score on a scale | Standard Deviation 6.37 |
| Placebo | Change From Baseline in Beck Scale for Suicide Ideation (BSSI) | Baseline: Week 0 | 17 score on a scale | Standard Deviation 5.78 |
| Placebo | Change From Baseline in Beck Scale for Suicide Ideation (BSSI) | End of Treatment: Week 4 | 10.57 score on a scale | Standard Deviation 7.26 |
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.
Time frame: 1 week
Population: Statistical outliers and motion-corrupted neuroimaging data were removed from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Uridine | Change From Baseline in Brain Gamma-Aminobutyric Acid (GABA)/NAA Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | 0.00113 ratio of GABA/NAA | Standard Deviation 0.0327 |
| Placebo | Change From Baseline in Brain Gamma-Aminobutyric Acid (GABA)/NAA Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | 0.00564 ratio of GABA/NAA | Standard Deviation 0.0279 |
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.
Time frame: 4 weeks
Population: Participants who were non-adherent to the study protocol or had medication changes throughout the clinical trial were removed from this analysis.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Uridine | Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline: Week 0 | 13.69 score on a scale | Standard Deviation 2.04 |
| Uridine | Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | End of Treatment: Week 4 | 8.27 score on a scale | Standard Deviation 6.45 |
| Placebo | Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | Baseline: Week 0 | 14.46 score on a scale | Standard Deviation 2.73 |
| Placebo | Change From Baseline in Columbia-Suicide Severity Rating Scale (C-SSRS) | End of Treatment: Week 4 | 10.87 score on a scale | Standard Deviation 5.2 |
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.
Time frame: 1 week
Population: Statistical outliers and motion-corrupted neuroimaging data were removed from this analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Uridine | Change From Baseline in Brain Total Choline/N-acetylaspartate (NAA) Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | 0.00461 ratio of tCho/NAA | Standard Deviation 0.012 |
| Placebo | Change From Baseline in Brain Total Choline/N-acetylaspartate (NAA) Levels, Measured With Proton-1 Magnetic Resonance Spectroscopy (1H-MRS) Neuroimaging | -0.00117 ratio of tCho/NAA | Standard Deviation 0.0106 |