Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT04127409 |
| Other study ID # |
GR15-0981 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2015 |
| Est. completion date |
June 30, 2020 |
Study information
| Verified date |
November 2023 |
| Source |
Royal College of Surgeons, Ireland |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Eating oily fish containing long chain seafood-derived omega-3 polyunsaturated fatty acids
(PUFAs) protects against heart attacks and strokes. Hence most national and international
guidelines now recommend that adults eat at least 2 servings per week of oily fish. However
uptake of these recommendations is poor - many people do not eat seafood at all. A number of
factors probably contribute to this poor compliance with guidelines; limited availability and
costs of oily fish; distaste for oily fish; and concern about toxins in such fish. An Irish
company, Devenish Nutrition, offers a possible alternative solution - by feeding omega-3
PUFA-enriched feeds to chicken, Devenish Nutrition have demonstrated that the resultant
chicken meat and eggs are enriched in omega-3 PUFAs. A recently completed small study, with
30 participants, showed that 5 weeks of eating omega-3 PUFA enriched chicken resulted in
increased blood levels of omega-3 PUFAs. There were also beneficial effects on blood pressure
and on platelet stickiness. This study will be larger (including 160 participants) and longer
in duration (6 months). It will be a double-blind, controlled, randomized study. This will
allow testing whether eating omega-3 PUFA enriched chicken-meat regularly over a 6 month
period, results in even greater increments in blood levels of omega-3 PUFAs, and in greater
beneficial effects on cardiovascular risk factors. Beneficial effects of eating omega-3 PUFA
enriched eggs will also be assessed.
Description:
BACKGROUND
There are four long chain omega-3 polyunsaturated fatty acids (PUFAs). Alpha-linolenic acid
(ALA 18:3n-3) is found in plants. However the remaining three omega-3 PUFAs, which are longer
and more unsaturated (Eicosapentaenoic acid, EPA 20:5n-3, Docosapentaenoic acid, DPA 22:5n-3,
and Docosahexaenoic acid, DHA 22:6n-3), are in large part found in oily seafood
Consumption of oily fish, and of long chain seafood-derived omega-3 polyunsaturated fatty
acids (PUFAs), has been strongly and consistently associated with reduced cardiovascular
morbidity and mortality. In a 2011 "State of the Art Paper" Mozaffarian and colleagues
concluded that "current data provide strong concordant evidence that long chain (seafood) n-3
PUFA are bioactive compounds that reduce risk of cardiac death".
Seafood derived omega-3 PUFAs influence a myriad of molecular pathways including membrane
structure, ion channel properties, genetic regulation, hepatic fatty acid metabolism,
eicosanoid and inflammatory mediator synthesis. It appears likely that the beneficial effects
of omega-3 PUFAs are mediated through downstream effects on a range of cardiovascular risk
factors including blood pressure, heart rhythm, lipid levels, inflammation, and lastly
thrombotic tendency through effects on platelet function. The omega-3 fatty acid
docosahexaenoic acid (DHA) is proven essential to pre and postnatal brain development while
eicosapentaenoic acid (EPA) is more influential on behaviour and mood.
Because of the strong evidence of benefits of seafood derived omega-3 PUFAs, most national
and international guidelines now recommend that adults eat at least 2 servings/week of oily
fish (>250 mg/day of long-chain omega-3 PUFAs). However uptake of these recommendations is
poor - many people do not consume seafood at all, and approximately one-half of U.S adults
consume <60 mg/day of EPA+DHA. A number of factors probably contribute to this poor
compliance; limited availability and costs of oily fish; distaste for oily fish; and concern
about toxins in such fish including methylmercury, polychlorinated biphenyls and dioxins.
An Irish company, Devenish Nutrition, offers a possible alternative solution - by feeding
algae derived omega-3 PUFAs enriched feeds to broiler chicken, Devenish Nutrition have
demonstrated that the resultant chicken meat is enriched in EPA, DPA and DHA. Furthermore
there was no detrimental effect to bird performance or on taste. Omega-3 enriched eggs are
currently commercially available (Skea Egg Farms Ltd, Dungannon, Tyrone), and are produced in
a similar fashion, through feeding omega-3 PUFAs enriched feeds to hens.
In a just completed pilot study, portions of omega-3 PUFA enriched chicken-meat were eaten,
three times weekly for five weeks, by 30 healthy human volunteers. Plasma levels of the 3
seafood derived omega-3 PUFAs increased from 82 ug/g at baseline to 93 ug/g at five weeks
(12% increment, p=0.006), and the red cell omega-3 index (sum of EPA and DHA expressed as
percentage of total fatty acids in erythrocyte membranes) increased from 4.9% to 5.1% (p =
ns). At 5 weeks, two secondary end-points, blood pressure (BP) and platelet reactivity, had
declined significantly in the 30 healthy volunteers - clinic systolic BP reduced from 116 to
113 mmHg (p = 0.014), and urinary thromboxane reduced from 1435 to 1024 pg/mg creatinine (p =
0.037).
In this double-blind, controlled, randomized study, the investigators intend to test whether
eating of omega-3 PUFA enriched chicken-meat over a 6 month period, results in greater
increments in plasma and red cell levels of omega-3 PUFAs, and in greater beneficial effects
on cardiovascular risk factors and on cognitive function and mood. In a second limb to this
study the investigators will test for additional beneficial effects in humans of consumption
of omega-3 PUFA enriched eggs.
The red cell omega-3 index was chosen as the primary outcome for this study, because of its
lessor variability over time compared to plasma values, and because of its proven correlation
with EPA and DHA levels in human cardiac tissue, and in multiple relevant organs in animal
models.
STUDY AIMS AND OBJECTIVES
The two co-primary objectives are to test whether;
- The consumption of 3 servings of omega-3 PUFA-enriched chicken-meat per week, over a 6
month period, results in measurably higher red cell levels of EPA and DHA.
- The consumption of 3 omega-3 enriched eggs per week, over a 6 month period, results in
measurably higher red cell levels of EPA and DHA.
Secondary objectives include the evaluation of:
- Whether the consumption of 3 servings of omega-3 PUFA-enriched chicken-meat per week,
over a 6 month period, results in measurably higher plasma levels of EPA and DHA.
- Whether the consumption of 3 omega-3 enriched eggs per week, over a 6 month period,
results in measurably higher plasma levels of EPA and DHA.
- Whether the consumption of 3 servings of omega-3 PUFA-enriched chicken-meat per week,
over a 6 month period, reduces BP, heart rate, lipid levels, inflammation and/or
thrombotic tendencies.
- Whether the consumption of 3 omega-3 enriched eggs per week, over a 6 month period,
reduces BP, heart rate, lipid levels, inflammation and/or thrombotic tendencies.
- Whether the consumption of 3 servings of omega-3 PUFA-enriched chicken-meat per week,
over a 6 month period, results in improved cognitive function and/or mood.
- Whether the consumption of 3 omega-3 enriched eggs per week, over a 6 month period,
results in improved cognitive function and/or mood.
STUDY PARTICIPANTS
160 participants will be recruited to the study through hospital out-patient departments,
general practices, and by public advertisement by 2 clinical sites in Dublin, Beaumont and
Connolly Hospitals, both of whom are part of the RCSI Teaching Hospital Network Academic
Health Centre.
STUDY DESIGN
This will be a controlled, double-blind randomised study. Using a 2X2 factorial design, 160
healthy participants will be randomised to eat at least 3 portions/week of omega-3-PUFA
enriched (or control) chicken-meat, and to eat at least 3 omega-3-PUFA enriched (or Control)
eggs/week, for 6 months
STUDY CONDUCT
Prior to recruitment to the study, potential participants will be given comprehensive
information about the study, unlimited time to study this written information, and all
questions will be answered by a study investigator. If the potential participant is satisfied
with this information, and wishes to participate, written informed consent will be taken.
At the screening visit, a comprehensive lifestyle and medical history will be taken. A food
frequency questionnaire will be completed to capture food intake over the previous year.
Clinic and ambulatory blood pressure and heart rate will also be measured, as will height,
weight, body mass index, and waist circumference. Finally, assessment of cognitive function
and mood will be carried out by a battery of tests. A fasting blood sample will be taken to
allow measurement of plasma and red cell levels of EPA and DHA, full blood count (platelet
count), renal function, liver function, plasma lipid levels, inflammation (high sensitivity
C-reactive protein), platelet function (platelet aggregation and serum thromboxane), and DNA
extraction. Urine sampling will also occur to allow assessment of platelet turnover (urinary
thromboxane/creatinine ratio), and renal function (microalbuminuria).
After all screening assessments have been completed, and if all inclusion and exclusion
criteria are satisfied, participants will be randomized to eating omega-3 PUFA enriched
chicken-meat or control chicken-meat, and to omega-3 PUFA enriched eggs or control eggs, for
the 6 month period. Randomization will be stratified according to gender.
Omega-3 PUFA enriched chicken (whole chickens, breasts, thighs, drums and wings) and eggs, or
the appropriate control chicken and control eggs, will be delivered to the homes of study
participants at regular intervals (weekly or two-weekly), so that both they, and up to four
family members, will be able to eat at least 3 servings per week of chicken meat, and at
least 3 eggs weekly over the 6 month study period. The chicken-meat will be delivered frozen,
and the eggs will be delivered refrigerated.
Participants will be asked to avoid the taking of omega-3 PUFA supplements,
antihypertensives, lipid lowering therapy, antiplatelet therapy such as aspirin, or any
non-steroidal anti-inflammatory drugs (nurofen, indomethacin, diclofenac etc) for the
duration of the study. If an analgesic is needed paracetamol may be used.
Participants will be asked to fast, not drink tea or coffee, not smoke and not engage in
intense exercise from midnight (minimum 8 hours) prior to the screening (baseline) visit, and
prior to the 3 and 6 month visits. Participants may drink water and take essential
medications on these mornings. At both the 3 month and the 6 month (final) visit, all
baseline assessments will be repeated. At months 1,2,4 and 5 a telephone call will be made to
check on participant well-being (absence of adverse events), and on compliance with diet.
STATISTICAL ANALYSIS
Standard summary statistics (mean, standard deviation, median, range, %) will be used to
describe baseline characteristics of the participants.
Changes in both the primary and the secondary end-points, at 3 and 6 months from baseline,
with consumption of omega-3 enriched chicken-meat and eggs, will be compared to the changes
recorded with consumption of control chicken-meat and eggs, using two-way ANOVA.
SAMPLE SIZE CONSIDERATIONS
The primary objective of this study is to test whether the consumption of 3 servings per week
of omega-3 PUFA-enriched chicken-meat and/or the consumption of 3 omega-3 PUFA enriched eggs,
over a 6 month period results in measurably higher red levels of EPA and DHA (red cell
omega-3 index). From the recently completed pilot study, wherein 30 healthy community
dwelling subjects ate three servings per week of omega-3-PUFA enriched chicken meat for 5
weeks, the baseline omega-3 index was 4.93% (standard deviation 1.11%). This increased to
5.12% (1.18%) after 5 weeks. The mean difference was 0.19% (0.44%). In order to achieve a
power of 95% to detect a difference of 1% in the omega-3 index between those eating control
and enriched chicken-meat, and between those eating control and enriched eggs, at a
2-sided-level of 0.05, a sample size of 132 participants is required. To allow for potential
losses to follow-up, enrollment of 160 participants is planned.
