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

Cardiovascular Diseases Clinical Trial

Official title:

BioBehavioral Studies of Cardiovascular Disease

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00663871
• Other study ID #: STUDY19060029
• Secondary ID: 2P01HL040962R01A
• Status: Completed
• Phase: N/A
• Start date: June 2008
• Est. completion date: October 2012

Study information

• Verified date: May 2021
• Source: University of Pittsburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.)

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: October 2012
• Est. primary completion date: October 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 30 Years to 55 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases
• Inflammation
• Mood Disorders

Intervention

Dietary Supplement:
• Fish Oil
Participants will take 2 grams (1400 mg EPA and DHA) of fish oil supplements on a daily basis.
• Soybean Oil (Placebo)
Participants will take 2 grams of soybean oil supplements on a daily basis.

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania

Sponsors (4)

Lead Sponsor	Collaborator
University of Pittsburgh	National Center for Complementary and Integrative Health (NCCIH), National Heart, Lung, and Blood Institute (NHLBI), Office of Dietary Supplements (ODS)

Country where clinical trial is conducted

United States, 

References & Publications (12)

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. — View 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. Epub 2007 Jun 2. — View 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. Epub 2007 Ma — View 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. Epub 2007 Nov 8. — View 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 F — View 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. Psych — View 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. Psycho — View 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. — View 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 — View 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. — View 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. — View 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. Review. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Structural & Functional MRI	Measures of brain structure and function from magnetic resonance imaging	Baseline and month 4
Primary	Circulating Serum Interleukin-6 (IL-6)	Systemic inflammation: fasting serum Interleukin-6 (IL-6)	Baseline and Month 4
Primary	C-reactive Protein (CRP)	fasting serum C-reactive protein (CRP) in milligrams per liter (mg/L)	baseline and month 4
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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