Clinical trial NCT00663871: Evaluating the Effects of Omega-3 Fatty Acids on Heart Disease and Behavior
Official title: BioBehavioral Studies of Cardiovascular Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cardiovascular Diseases
Mood Disorders
Inflammation
Keywords: Fish Oil
Omega-3 fatty acids
Affect
Depression
Anger
Nutrition
Impulsivity
Aggression
Cognition
Behavior
Lead sponsor: University of Pittsburgh
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: National Center for Complementary and Integrative Health (NCCIH)
name: Office of Dietary Supplements (ODS)
First posted: 2008-04-22
Enrollment: 272
Sex: ALL
Minimum age (years): 30
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.)

Eligibility criteria: 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

Primary outcomes:
measure: Circulating Serum Interleukin-6 (IL-6)
timeFrame: Baseline and Month 4
measure: C-reactive Protein (CRP)
timeFrame: baseline and month 4
measure: Negative Affect
timeFrame: baseline and month 4
measure: Impulsivity
timeFrame: baseline and month 4
measure: Aggression
timeFrame: baseline and month 4
measure: Hostility, Barefoot Score
timeFrame: baseline and month 4
measure: Trait Anger
timeFrame: baseline and month 4
measure: Anger Expression
timeFrame: baseline and month 4
measure: Type A, Total Score
timeFrame: baseline and month 4
measure: Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Paced Respiration
timeFrame: baseline and month 4
measure: High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration
timeFrame: baseline and month 4
measure: Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Paced Respiration
timeFrame: baseline and month 4
measure: Mean Successive Difference in Inter-beat Intervals Natural Log Transformed Unpaced Respiration
timeFrame: baseline and month 4
measure: High Frequency (.12 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration
timeFrame: baseline and month 4
measure: Total Power (0 to .40 Hz) Heart Rate Variability Natural Log Transformed Unpaced Respiration
timeFrame: baseline and month 4
Secondary outcomes:
measure: Executive Function
timeFrame: Baseline and Month 4
measure: Learning / Episodic Memory
timeFrame: Baseline and Month 4
measure: Psychomotor Speed
timeFrame: Baseline and Month 4
measure: Fluid Intelligence
timeFrame: Baseline and Month 4
measure: Moderation of Effects of Fish Oil on Inflammatory Markers by Select Genetic Polymorphisms
timeFrame: Measured at Month 4
Other outcomes:
measure: Structural & Functional MRI
timeFrame: Baseline and month 4
Locations:
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
Study officials:
affiliation: University of Pittsburgh
name: Matthew F. Muldoon, MD, MPH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Muldoon MF, Ryan CM, Yao JK, Conklin SM, Manuck SB. Long-chain omega-3 fatty acids and optimization of cognitive performance. Mil Med. 2014 Nov;179(11 Suppl):95-105. doi: 10.7205/MILMED-D-14-00168.
citation: Leckie RL, Lehman DE, Gianaros PJ, Erickson KI, Sereika SM, Kuan DCH, Manuck SB, Ryan CM, Yao JK, Muldoon MF. The effects of omega-3 fatty acids on neuropsychological functioning and brain morphology in mid-life adults: a randomized clinical trial. Psychol Med. 2020 Oct;50(14):2425-2434. doi: 10.1017/S0033291719002617. Epub 2019 Oct 4.
citation: Muldoon MF, Laderian B, Kuan DC, Sereika SM, Marsland AL, Manuck SB. Fish oil supplementation does not lower C-reactive protein or interleukin-6 levels in healthy adults. J Intern Med. 2016 Jan;279(1):98-109. doi: 10.1111/joim.12442. Epub 2015 Oct 26.
citation: Ginty AT, Muldoon MF, Kuan DCH, Schirda B, Kamarck TW, Jennings JR, Manuck SB, Gianaros PJ. Omega-3 Supplementation and the Neural Correlates of Negative Affect and Impulsivity: A Double-Blind, Randomized, Placebo-Controlled Trial in Midlife Adults. Psychosom Med. 2017 Jun;79(5):549-556. doi: 10.1097/PSY.0000000000000453.
citation: Cipollina C, Salvatore SR, Muldoon MF, Freeman BA, Schopfer FJ. Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives. PLoS One. 2014 Apr 15;9(4):e94836. doi: 10.1371/journal.pone.0094836. eCollection 2014.
citation: Muldoon MF, Ryan CM, Sheu L, Yao JK, Conklin SM, Manuck SB. Serum phospholipid docosahexaenonic acid is associated with cognitive functioning during middle adulthood. J Nutr. 2010 Apr;140(4):848-53. doi: 10.3945/jn.109.119578. Epub 2010 Feb 24.
citation: Liu JC, Conklin SM, Manuck SB, Yao JK, Muldoon MF. Long-chain omega-3 fatty acids and blood pressure. Am J Hypertens. 2011 Oct;24(10):1121-6. doi: 10.1038/ajh.2011.120. Epub 2011 Jul 14.
citation: Conklin SM, Harris JI, Manuck SB, Yao JK, Hibbeln JR, Muldoon MF. Serum omega-3 fatty acids are associated with variation in mood, personality and behavior in hypercholesterolemic community volunteers. Psychiatry Res. 2007 Jul 30;152(1):1-10. doi: 10.1016/j.psychres.2006.10.006. Epub 2007 Mar 23.
citation: Conklin SM, Gianaros PJ, Brown SM, Yao JK, Hariri AR, Manuck SB, Muldoon MF. Long-chain omega-3 fatty acid intake is associated positively with corticolimbic gray matter volume in healthy adults. Neurosci Lett. 2007 Jun 29;421(3):209-12. doi: 10.1016/j.neulet.2007.04.086. Epub 2007 Jun 2.
citation: Conklin SM, Manuck SB, Yao JK, Flory JD, Hibbeln JR, Muldoon MF. High omega-6 and low omega-3 fatty acids are associated with depressive symptoms and neuroticism. Psychosom Med. 2007 Dec;69(9):932-4. doi: 10.1097/PSY.0b013e31815aaa42. Epub 2007 Nov 8.
citation: Conklin SM, Runyan CA, Leonard S, Reddy RD, Muldoon MF, Yao JK. Age-related changes of n-3 and n-6 polyunsaturated fatty acids in the anterior cingulate cortex of individuals with major depressive disorder. Prostaglandins Leukot Essent Fatty Acids. 2010 Feb-Mar;82(2-3):111-9. doi: 10.1016/j.plefa.2009.12.002. Epub 2010 Jan 8.
citation: Muldoon MF, Erickson KI, Goodpaster BH, Jakicic JM, Conklin SM, Sekikawa A, Yao JK, Manuck SB. Concurrent physical activity modifies the association between n3 long-chain fatty acids and cardiometabolic risk in midlife adults. J Nutr. 2013 Sep;143(9):1414-20. doi: 10.3945/jn.113.174078. Epub 2013 Jul 24.