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

Primary Purpose

Suicide

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Study Juice
Placebo Juice
Sponsored by
Medical University of South Carolina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Suicide focused on measuring Adults, Suicidality

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion criteria- Primary study

  1. 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.)
  2. age 18 - 90
  3. within the participant's medical history, either

    1. a suicide attempt in the last 6 months, or
    2. 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
    3. an inpatient admission with suicide risk in the last 6 months, or
    4. 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
    5. 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
    6. a score of 0 or greater on the Implicit Associations Test-Suicide (IAT-S), or
    7. > or = 9 on the Beck Hopelessness Scale (BHS) and psychiatrist review of participant medical history and physical
  4. participant can safely eat walnuts, pecans, almonds, peanuts and all other nuts
  5. participant can safely eat apples, peaches, pears, pomegranates, aronia, jackfruit, and passion fruit
  6. participant can safely eat the herb rosemary, and the fish salmon, trout and cod
  7. participant can safely drink and eat food that contain whey and/or milk protein
  8. willingness to drink the juice boxes 3 times each day for 6 months
  9. have a stable residence with adequate space to store the juice
  10. capacity to provide written informed consent

Additional inclusion criteria for Depressive Symptoms sub-analysis

  1. enrollment in the primary study of suicide risk reduction
  2. a Beck Depression Inventory ≥30
  3. a diagnosis of a depressive disorder

Additional inclusion criteria for Alcohol and Nicotine use sub-analysis

  1. enrollment in the primary study of suicide risk reduction
  2. diagnosis of an alcohol use disorder or "at risk drinking patterns"
  3. self-report of smoking >10 cigarettes/d.

Exclusion criteria-

  1. unstable medical conditions requiring immediate attention or medical conditions that preclude potential study participation for the duration of the study
  2. 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)
  3. persons who have received a diagnosis of diabetes
  4. those taking Isotretinoin (Accutane)
  5. allergy, hypersensitivity, or intolerance to fish oils or omega-3 fats
  6. allergy, hypersensitivity, or intolerance to Macadamia nuts or any nuts such as almonds, walnuts, pecans, peanuts, etc.
  7. allergy, hypersensitivity, or intolerance to apples, peaches, pears, pomegranates, aronia, jackfruit, and passion fruit
  8. allergy, hypersensitivity, or intolerance to the herb rosemary, and the fish: salmon, trout and cod
  9. allergy, hypersensitivity, or intolerance to whey and/or milk protein
  10. life threatening medical conditions or life expectancy of less than 6 months
  11. pregnancy or lactation or intention to become pregnant within the next 12 months
  12. acute intoxication or withdrawal from alcohol or other substances (to be determined by a clinical team member)
  13. a cognitive impairment severe enough to preclude informed consent or valid responses on self-report questionnaires
  14. Body Mass Index (BMI) <18 or >45
  15. evidence of disordered eating or risk of malnutrition based on the Eating Attitudes Test (EAT-26)
  16. relapsing of remitting Multiple Sclerosis
  17. unstable or rapidly progressive neurological disease
  18. history of significant behavioral instability
  19. participating in another research study
  20. regular use of anticoagulants such as high dose aspirin, warfarin or Coumadin
  21. 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

Sites / Locations

  • Medical University of South Carolina

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Study Juice

Placebo Juice

Arm Description

3,300 mg of Omega-3 HUFAs per day for 6 months Other names: none

3,300 mg of macadamia nut oil per day for 6 months Other names: none

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
July 2, 2013
Last Updated
June 9, 2018
Sponsor
Medical University of South Carolina
Collaborators
U.S. Army Medical Research and Development Command
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1. Study Identification

Unique Protocol Identification Number
NCT01901887
Brief Title
The Better Resiliency Among Veterans With Omega-3's (BRAVO) Study
Acronym
BRAVO
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Terminated
Why Stopped
low recruitment
Study Start Date
March 1, 2014 (Actual)
Primary Completion Date
August 30, 2016 (Actual)
Study Completion Date
August 30, 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of South Carolina
Collaborators
U.S. Army Medical Research and Development Command

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Suicide
Keywords
Adults, Suicidality

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
125 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Study Juice
Arm Type
Experimental
Arm Description
3,300 mg of Omega-3 HUFAs per day for 6 months Other names: none
Arm Title
Placebo Juice
Arm Type
Placebo Comparator
Arm Description
3,300 mg of macadamia nut oil per day for 6 months Other names: none
Intervention Type
Drug
Intervention Name(s)
Study Juice
Other Intervention Name(s)
SMARTFISH® Nutrifriend 1100, Omega-3 formulated juice
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Placebo Juice
Other Intervention Name(s)
Other names: Smartfish (placebo juice)
Intervention Description
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.
Primary Outcome Measure Information:
Title
Impact of omega-3 HUFA supplementation on suicidal behaviors and thinking among adults.
Description
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.
Time Frame
6 months
Secondary Outcome Measure Information:
Title
Impact of omega-3 HUFA supplementation on symptoms of negative affect associated with suicide risk among adults.
Description
Examine to see if dietary supplementation with omega-3 HUFAs reduces symptoms of perceptions of daily stress, anxiety, depression, and hopelessness.
Time Frame
6 months
Title
Impact of omega-3 HUFA supplementation on symptoms of post-traumatic stress disorder (PTSD) associated with suicide risk among adults.
Description
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.
Time Frame
6 months
Title
Impact of omega-3 HUFA supplementation on symptoms of cognitive functioning associated with suicide risk among adults.
Description
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.
Time Frame
6 months
Other Pre-specified Outcome Measures:
Title
Impact of omega-3 HUFA supplementation among subjects with moderate to severe depressive symptoms to evaluate efficacy for clinically significant depressive symptoms.
Description
Examine to see if higher blood levels of omega-3 HUFAs correlate with scores on the Beck Depression Inventory, and increase likelihood of a 50% reduction in depressive symptoms.
Time Frame
6 months
Title
Impact of dietary supplementation with omega-3 fatty acids on alcohol consumption in suicidal adults with alcohol use disorders.
Description
Examine to see if dietary supplementation with omega-3 HUFAs decreases alcohol use in alcohol-dependent individuals; decreases alcohol consumption in non-alcohol-dependent individuals who endorse risky alcohol use in the past 12 months; decreases obsessive and compulsive thoughts about alcohol; and, decreases use of cigarettes among persons who smoke >10 cigarettes/day. Examine to see if decreases in alcohol consumption are associated with decreases in negative affect and impulsivity; and, if they are associated with decreased suicidal ideation/behaviors.
Time Frame
6 months
Title
Impact of an omega-3 HUFA intervention on prefrontal hypo activation to risky decision-making and recall of past suicidal events in suicide attempters, using functional Magnetic Resonance Imaging (fMRI).
Description
Determine if dietary supplementation with omega-3 fatty acids increases activation of frontal brain regions associated with risky decision-making (e.g., orbitofrontal cortex); and those associated with suicide attempt recall (e.g., medial prefrontal cortex.)
Time Frame
6 months
Title
Suicidal ideation and behavior at 6-months post treatment-initiation by fMRI.
Description
Determine if increases in frontal activation to risky decision-making and recall of past suicidal events from baseline to 6-months post treatment-initiation are associated with less suicidal ideation and behavior at > 6-months post treatment-initiation.
Time Frame
6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bernadette Marriott, PhD
Organizational Affiliation
Medical University of South Carolina
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Joseph R Hibbeln, MD
Organizational Affiliation
LMBB, NIAAA, NIH
Official's Role
Principal Investigator
Facility Information:
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
9643729
Citation
Hibbeln JR. Fish consumption and major depression. Lancet. 1998 Apr 18;351(9110):1213. doi: 10.1016/S0140-6736(05)79168-6. No abstract available.
Results Reference
background
PubMed Identifier
9715354
Citation
Hibbeln JR, Linnoila M, Umhau JC, Rawlings R, George DT, Salem N Jr. Essential fatty acids predict metabolites of serotonin and dopamine in cerebrospinal fluid among healthy control subjects, and early- and late-onset alcoholics. Biol Psychiatry. 1998 Aug 15;44(4):235-42. doi: 10.1016/s0006-3223(98)00141-3.
Results Reference
background
PubMed Identifier
16949263
Citation
McNamara RK, Carlson SE. Role of omega-3 fatty acids in brain development and function: potential implications for the pathogenesis and prevention of psychopathology. Prostaglandins Leukot Essent Fatty Acids. 2006 Oct-Nov;75(4-5):329-49. doi: 10.1016/j.plefa.2006.07.010. Epub 2006 Sep 1.
Results Reference
background
PubMed Identifier
21367944
Citation
Blasbalg TL, Hibbeln JR, Ramsden CE, Majchrzak SF, Rawlings RR. Changes in consumption of omega-3 and omega-6 fatty acids in the United States during the 20th century. Am J Clin Nutr. 2011 May;93(5):950-62. doi: 10.3945/ajcn.110.006643. Epub 2011 Mar 2.
Results Reference
background
PubMed Identifier
19136836
Citation
Hibbeln JR. Depression, suicide and deficiencies of omega-3 essential fatty acids in modern diets. World Rev Nutr Diet. 2009;99:17-30. doi: 10.1159/000192992. Epub 2009 Jan 9. No abstract available.
Results Reference
background
PubMed Identifier
33884617
Citation
Witt KG, Hetrick SE, Rajaram G, Hazell P, Taylor Salisbury TL, Townsend E, Hawton K. Psychosocial interventions for self-harm in adults. Cochrane Database Syst Rev. 2021 Apr 22;4(4):CD013668. doi: 10.1002/14651858.CD013668.pub2.
Results Reference
derived

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

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