The Better Resiliency Among Veterans With Omega-3's (BRAVO) Study

Study Overview
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Brief Summary
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The BRAVO study seeks to determine if dietary supplementation with omega-3 highly unsaturated fatty acids (omega-3 HUFAs) reduces the risk for serious suicidal behaviors, suicidal thinking, negative emotions, and symptoms associated with suicide risk, in a Veteran and non-Veteran population that is at risk for suicidal behaviors. This study seeks to evaluate the efficacy of omega-3 HUFAs among a representative population of US Veterans and non-Veterans already receiving appropriate medical care so that if successful, these results can be readily applied to broader populations in the US.

Detailed Description
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The BRAVO study seeks to determine if dietary supplementation with omega-3 highly unsaturated fatty acids (omega-3 HUFAs) reduces the risk for serious suicidal behaviors, suicidal thinking, negative emotions, and symptoms associated with suicide risk, in a Veteran and non-Veteran population that is at risk for suicidal behaviors. Changes in cognitive processes specific to suicide risk will be evaluated, including implicit associations, response inhibition and sustained attention. Sub-analyses will evaluate efficacy in reducing depressive symptoms, alcohol and nicotine use among Veterans and non-Veterans with concomitant significant depressive symptoms, and alcohol and nicotine use disorders. In addition, a sub-study will utilize functional magnetic resonance imaging (fMRI) to evaluate the neuropsychological and neurophysiological effects of the omega-3 HUFAs. This study seeks to evaluate the efficacy of omega-3 HUFAs among a representative population of US Veterans and non-Veterans already receiving appropriate medical care so that if successful, these results can be readily applied to broader populations in the US.

Official Title
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The Better Resiliency Among Veterans With Omega-3's (BRAVO) Study: A Double Blind, Placebo-Controlled Trial of Omega-3 Fatty Acid Supplementation Among Military Veterans

Conditions
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Suicide

Intervention / Treatment
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* Drug: Study Juice
* Drug: Placebo Juice


Participation Criteria
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Eligibility Criteria
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Inclusion criteria- Primary study a Veteran or non-Veteran identified as being at risk for suicide and presently under the care of a mental healthcare provider (A release of information from his/her mental healthcare provider is required.) age 18 - 90 within the participant's medical history, either a suicide attempt in the last 6 months, or a suicide attempt during the adult lifetime AND current diagnosis of an episode of depression as diagnosed on the Mini International Neuropsychiatric Interview (MINI), or an inpatient admission with suicide risk in the last 6 months, or an inpatient admission with suicide risk during the adult lifetime AND current diagnosis of an episode of depression as diagnosed on the Mini International Neuropsychiatric Interview (MINI), or positive suicidal behavior or ideation based on a psychiatrist- administered Columbia-Suicide Severity Rating Scale (C-SSRS) and psychiatrist review of participant medical history and physical], or a score of 0 or greater on the Implicit Associations Test-Suicide (IAT-S), or > or = 9 on the Beck Hopelessness Scale (BHS) and psychiatrist review of participant medical history and physical participant can safely eat walnuts, pecans, almonds, peanuts and all other nuts participant can safely eat apples, peaches, pears, pomegranates, aronia, jackfruit, and passion fruit participant can safely eat the herb rosemary, and the fish salmon, trout and cod participant can safely drink and eat food that contain whey and/or milk protein willingness to drink the juice boxes 3 times each day for 6 months have a stable residence with adequate space to store the juice capacity to provide written informed consent Additional inclusion criteria for Depressive Symptoms sub-analysis enrollment in the primary study of suicide risk reduction a Beck Depression Inventory ≥30 a diagnosis of a depressive disorder Additional inclusion criteria for Alcohol and Nicotine use sub-analysis enrollment in the primary study of suicide risk reduction diagnosis of an alcohol use disorder or at risk drinking patterns self-report of smoking >10 cigarettes/d. Exclusion criteria- unstable medical conditions requiring immediate attention or medical conditions that preclude potential study participation for the duration of the study history of seizures, except for: febrile seizures during childhood history of a single seizure episode as an adult if not being maintained on anti-seizure medication; this single seizure must not be related to a primary seizure disorder (must not be epilepsy) persons who have received a diagnosis of diabetes those taking Isotretinoin (Accutane) allergy, hypersensitivity, or intolerance to fish oils or omega-3 fats allergy, hypersensitivity, or intolerance to Macadamia nuts or any nuts such as almonds, walnuts, pecans, peanuts, etc. allergy, hypersensitivity, or intolerance to apples, peaches, pears, pomegranates, aronia, jackfruit, and passion fruit allergy, hypersensitivity, or intolerance to the herb rosemary, and the fish: salmon, trout and cod allergy, hypersensitivity, or intolerance to whey and/or milk protein life threatening medical conditions or life expectancy of less than 6 months pregnancy or lactation or intention to become pregnant within the next 12 months acute intoxication or withdrawal from alcohol or other substances (to be determined by a clinical team member) a cognitive impairment severe enough to preclude informed consent or valid responses on self-report questionnaires Body Mass Index (BMI) <18 or >45 evidence of disordered eating or risk of malnutrition based on the Eating Attitudes Test (EAT-26) relapsing of remitting Multiple Sclerosis unstable or rapidly progressive neurological disease history of significant behavioral instability participating in another research study regular use of anticoagulants such as high dose aspirin, warfarin or Coumadin take hypoglycemic agents Additional exclusion criteria for fMRI Study only (40 individuals) inability or unwillingness to participate in an fMRI scan presence of metallic objects in the body that would interfere with the scan pronounced claustrophobia body weight >300 pounds

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Study Juice<br>3,300 mg of Omega-3 HUFAs per day for 6 months Other names: none | Drug: Study Juice<br>* The intervention will be 3 boxes/day for 6 months of SMARTFISH® Nutrifriend 1100, a commercially available smoothie juice box containing 1,100 mg of omega-3 HUFAs/200 ml box (approximately 550 mg EPA and 550 mg DHA/box) for a total of 3,300 mg of omega-3 HUFAs/day (approximately 1,650 mg EPA and 1,650 mg DHA/day).<br>* Other names: Omega-3 formulated juice;|
| Placebo Comparator: Placebo Juice<br>3,300 mg of macadamia nut oil per day for 6 months Other names: none | Drug: Placebo Juice<br>* The placebo will be 3 boxes/day for 6 months of a placebo juice which will be identical to the study juice except that it will substitute 1,100 mg of macadamia nut oil/200 ml juice box in place of the omega-3 HUFAs for a total of 3,300 mg of macadamia nut oil/day.<br>* Other names: Other names: Smartfish (placebo juice);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of omega-3 HUFA supplementation on suicidal behaviors and thinking among adults. | Examine to see if dietary supplementation with omega-3 HUFAs results in fewer episodes of a New Episode of Significant Suicide Risk (NESSR)*, reduces symptom assessment scores for suicidality, reduces implicit associations with suicide and death, and improves performance scores on suicide related cognition tests. * A NESSR is defined as the occurrence of any of the following: a) a suicide death, or b) a suicide attempt, or c) an inpatient admission with suicide risk, or d) a new VA medical record flag for suicidality, or outside the VA system a clinical diagnostic equivalent (the Columbia-Suicide Severity Rating Scale) and psychiatrist review of participant medical history and physical. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Impact of omega-3 HUFA supplementation on symptoms of negative affect associated with suicide risk among adults. | Examine to see if dietary supplementation with omega-3 HUFAs reduces symptoms of perceptions of daily stress, anxiety, depression, and hopelessness. | 6 months | 
| Impact of omega-3 HUFA supplementation on symptoms of post-traumatic stress disorder (PTSD) associated with suicide risk among adults. | Examine to see if dietary supplementation with omega-3 HUFAs lowers the number of moderate to severe symptoms of PTSD, and decreases the severity of symptoms of PTSD among subjects with moderate to severe symptoms. | 6 months | 
| Impact of omega-3 HUFA supplementation on symptoms of cognitive functioning associated with suicide risk among adults. | Examine to see if dietary supplementation with omega-3 HUFAs improves sustained attention, response inhibition, and cognitive control; determine if changes in cognitive parameters are associated with changes in negative affect; and, determine if cognitive changes are associated with changes in suicide parameters. | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adults, Suicidality