Evaluating the Effects of Omega-3 Fatty Acids on Heart Disease and Behavior

Study Overview
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Brief Summary
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Omega-3 fatty acids are a certain kind of fish fat that has recently been shown to have health benefits. This study will examine the effectiveness of fish oil supplementation for reducing the early signs of heart disease risk and for improving mood, impulsivity, and anger levels.

Detailed Description
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Cardiovascular disease (CVD) is a broad term that includes diseases that affect the heart and blood vessels, including coronary heart disease, heart failure, high blood pressure, stroke and vascular dementia. CVD is the leading cause of death in the United States, resulting in 700,000 deaths each year. Preliminary research has shown that increased consumption of fish, specifically the omega-3 fatty acids found in fish oil, has beneficial effects in people with CVD. Fish oil may also have positive effects on the psychological health and well-being of people with psychiatric disorders. However, more research is needed to confirm the positive physical and psychological effects of fish oil in healthy adults. The purpose of this study is to explore potentail effects of fish oil supplementation on CVD mechanisms and risk markers, and on depressive symptoms, antagonistic disposition, and levels of impulsivity and aggression. This study will enroll healthy adults who habitually consume low quantities of long-chain omega-3 fatty acids. Participants will be randomly assigned to receive either fish oil supplements or placebo on a daily basis for 4 months. Study visits will occur at baseline and Months 2 and 4. At the baseline and Month 4 visits, participants will undergo the following measures as primary study aims: blood collection for inflammatory markers; heart rate and variability measurements; and interviews, psychological tests, and questionnaires to assess mood, disposition, impulsivity, and aggression. As secondary aims, we will test for any effects of fish oil on cognitive performance and, if a main effect on inflammatory markers is found, we will test for moderation by select genetic polymorphisms. As an exploratory aim, we will test for any effects of fish oil on structural or functional brain imaging. (This exploratory aim was mistakenly listed as a secondary aim at the time of trial registration.)

Official Title
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BioBehavioral Studies of Cardiovascular Disease

Conditions
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Cardiovascular Diseases, Mood Disorders, Inflammation

Intervention / Treatment
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* Dietary Supplement: Fish Oil
* Dietary Supplement: Soybean Oil (Placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Currently employed at least 25 hours a week, but does not regularly work the third shift (i.e., night shift) English is primary language Consumes less than 300 mg/day of long-chain omega-3 fatty acids. Exclusion Criteria: Serious allergy to fish (e.g., anaphylaxis, bronchospasm, serious skin reaction) History of atherosclerotic disease (e.g., myocardial infarction) or treatment of angina or claudication (e.g., angioplasty) Reported history of schizophrenia or bipolar disorder Long-term hepatitis Kidney failure Stroke or other neurological disorder Lung disease requiring drug treatment Stage 2 high blood pressure, defined as systolic blood pressure of 160 mm Hg or greater and diastolic blood pressure of 100 mm Hg or greater Alcohol consumption of more than five drinks per day each week (i.e., more than 35 alcoholic drinks each week) Pregnant or breastfeeding Currently taking any cardiovascular, psychotropic, glucocorticoid, lipid-lowering, insulin, or weight loss medications Currently taking fish oil supplements

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Fish Oil<br>Participants will take fish oil supplements daily for 4 months. | Dietary Supplement: Fish Oil<br>* Participants will take 2 grams (1400 mg EPA and DHA) of fish oil supplements on a daily basis.<br>* Other names: Omega-3 Life Formula (PharmaOmega);|
| Placebo Comparator: Placebo<br>Participants will take soybean oil (placebo) supplements daily for 4 months. | Dietary Supplement: Soybean Oil (Placebo)<br>* Participants will take 2 grams of soybean oil supplements on a daily basis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Circulating Serum Interleukin-6 (IL-6) | Systemic inflammation: fasting serum Interleukin-6 (IL-6) | Baseline and Month 4 | 
| C-reactive Protein (CRP) | fasting serum C-reactive protein (CRP) in milligrams per liter (mg/L) | baseline and month 4 | 
| Negative Affect | Negative affect questions adapted from the Positive and Negative Affect Schedule - Expanded Form administered via ecological momentary assessment. The minimum value is 1, and the maximum value is 6. A higher score are worse (more negative affect). | baseline and month 4 | 
| Impulsivity | Barratt Impulsiveness Scale. The minimum value is 34, and the maximum value is 120. A higher score suggests a worse outcome. | baseline and month 4 | 
| Aggression | Bus-Perry Aggression Questionnaire. The minimum value is 14, and the maximum value is 53. A higher score suggests a worse outcome. | baseline and month 4 | 
| Hostility, Barefoot Score | The 27-item Barefoot Hostility Scale. The minimum value is 1, and the maximum value is 30. A higher score suggests a worse outcome. | baseline and month 4 | 
| Trait Anger | State-Trait Anger Expression Inventory. The minimum value is 10, and the maximum value is 40. A higher score suggests a worse outcome. | baseline and month 4 | 
| Anger Expression | State-Trait Anger Expression Inventory. The minimum value is 0, and the maximum value is 72. A higher score suggests a worse outcome. | baseline and month 4 | 
| Type A, Total Score | Structured Interview - Type A Behavior Pattern using the Interpersonal Hostility Assessment Technique (IHAT). The minimum value is 0, and the maximum value is 12. A higher score suggests a worse outcome. | baseline and month 4 | 
| Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration | Mean successive difference in inter-beat intervals natural log transformed paced respiration in milliseconds | baseline and month 4 | 
| High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | High frequency (.12 to .40 Hz) heart rate variability natural log transformed paced respiration in Hertz units (Hz) | baseline and month 4 | 
| Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration | Total power (0 to .40 Hz) heart rate variability natural log transformed paced respiration in Hertz (Hz) units. | baseline and month 4 | 
| Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration | Mean successive difference in inter-beat intervals natural log transformed unpaced respiration in milliseconds (msec) | baseline and month 4 | 
| High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | High frequency (.12 to .40 Hz) heart rate variability natural log transformed unpaced respiration in Hertz (Hz) units | baseline and month 4 | 
| Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration | Total power (0 to .40 Hz) heart rate variability natural log transformed unpaced respiration in Hertz (Hz) units | baseline and month 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Executive Function | Executive function was comprised of trail making B - A time, digit span forward and digit span backward completions. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. | Baseline and Month 4 | 
| Learning / Episodic Memory | Learning/episodic memory was comprised of d' from the four word memory task and the average performance across all trials of the Rey auditory verbal learning test. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. | Baseline and Month 4 | 
| Psychomotor Speed | Psychomotor speed was comprised of trail making A time, Stroop word-only time and color-only time. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. | Baseline and Month 4 | 
| Fluid Intelligence | This outcome was based upon matrix reasoning task raw score, block design task raw score and spatial span forward raw score. Performance scores on each task were converted into Z-scores, and then averaged across tasks. The Z-score indicates the number of standard deviations away from the mean. A Z-score of 0 is equal to the mean with negative numbers indicating values lower than the mean and positive values higher. Higher Z scores indicate higher function (better outcome). The analysis compared changes in Z-scores between the two treatment groups. | Baseline and Month 4 | 
| Moderation of Effects of Fish Oil on Inflammatory Markers by Select Genetic Polymorphisms | Circulating serum concentrations of IL6 and CRP before and after supplementation with fish oil or placebo. | Measured at Month 4 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fish Oil, Omega-3 fatty acids, Affect, Depression, Anger, Nutrition, Impulsivity, Aggression, Cognition, Behavior