Uptake of an Omega-3 Oil in Healthy Adults

Study Overview
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Brief Summary
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The goal of this clinical trial is to compare the uptake of two different omega-3 fatty acid preparations in healthy adults. The main question it aims to answer is whether the two different preparations have the same uptake after single dose supplementation.

Detailed Description
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Participants will be asked to take capsules of the new phospholipids+ (PL+) omega-3 product (a combination product of krill oil and fish oil) in the morning with a low-fat breakfast. This product contains around 1250 mg eicosapentaenoic acid (EPA) + docosahexaenoic acid (DHA). Researchers will compare this group with another group that takes standard fish oil (FO) ethyl esters (EE, with the same amount of EPA+DHA) to see if there are differences in pharmacokinetic parameters, including incremental area under the curve (iAUC), the maximum concentration of (Cmax) and the time it takes for EPA, DHA and EPA+DHA to reach the maximum concentration (Tmax) in plasma.

Official Title
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Investigation of Uptake of Two Different Omega-3 Fatty Acid Products in Healthy Subjects - a Randomized, Two-way Cross-over Study

Conditions
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Absorption, Pharmacokinetics

Intervention / Treatment
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* Dietary Supplement: PL+ omega 3 fatty acids
* Dietary Supplement: FO EE fatty acids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males or females (1:1) aged 18 - 65 years Capable and willing to give written informed consent, which includes compliance with the requirements and restrictions listed in the consent form Have a low habitual consumption of fatty fish and seafood, defined as a frequency of twice per month or less No fish consumption at least two weeks prior to screening visit Omega-3 index (≤ 7 %) Non-smoker BMI: 18 to 32 kg/m2 Exclusion Criteria: Omega-3 supplementation history within the last 4 weeks Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases, i.e., diabetes, cardiovascular, pulmonary, hematologic, gastrointestinal, neurological, or infectious diseases which could confound the results of the study or put the subject at undue risk Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 365 days prior to baseline Pregnancy, breast feeding or intention to become pregnant during the study (a pregnancy test will be conducted during screening and visits 1-2) General Safety & Laboratory Exclusion Criteria. Patients will be excluded from the study based on the following criteria: Haemoglobin: < 12.0 g/dL (women); < 13.5 g/dL (men) Platelets: < 150 x 103/μL Leukocytes < 4,4 x 103/mm3 Aspartate transaminase (AST) or alanine transaminase (ALT) within the normal range Serum creatine within the normal range or further for this study clinically relevant abnormal laboratory findings at screening Significant changes in lifestyle or medication (within last 2 months) Chronic intake of substances affecting blood coagulation (e.g. acetylic acid, anticoagulants (e.g. Marcumar), diuretics, thiazides), which in the investigator's opinion would impact subject safety Difficulty swallowing capsules or predicted inability to swallow the study products Individuals who have made a blood donation in excess of 500 mL or who had excess blood loss within the 4 months before the study starts Individuals who are currently enrolled in an ongoing clinical trial or who have been an active participant in a clinical trial within the last 4 weeks A known allergy or hypersensitivity to any of the ingredients of the study products Not willing to abstain from fish consumption or foods/oils high in omega-3 fatty acids Subjects considered inappropriate for the study by investigators, including subjects who are unable or unwilling to show compliance with the protocol

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: randomized, two-way cross-over study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active group<br>This group will receive a single dose of the PL+ omega 3 fatty acids capsules first, then receive a single dose of the standard FO EE omega 3 fatty acids capsules. Wash-out period is 2 weeks between treatments. | Dietary Supplement: PL+ omega 3 fatty acids<br>* PL+ omega 3 fatty acids is a food supplement that combines krill oil and FO EE. The dose will be around 1250 mg EPA+DHA.<br>Dietary Supplement: FO EE fatty acids<br>* A conventional fish oil food supplement containing EPA and DHA in the EE form. The dose will be 1250 mg EPA+DHA.<br>|
| Placebo Comparator: Placebo group<br>This group will receive a single dose of the standard FO EE omega 3 fatty acids capsules first, then receive a single dose of the PL+ omega 3 fatty acids capsules. Wash-out period is 2 weeks between treatments. | Dietary Supplement: PL+ omega 3 fatty acids<br>* PL+ omega 3 fatty acids is a food supplement that combines krill oil and FO EE. The dose will be around 1250 mg EPA+DHA.<br>Dietary Supplement: FO EE fatty acids<br>* A conventional fish oil food supplement containing EPA and DHA in the EE form. The dose will be 1250 mg EPA+DHA.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of iAUC of EPA+DHA from 0 to 12 hours (iAUC0-12h) between two study products | Blood concentrations of EPA + DHA in plasma at 0h and 12h will be analyzed, and determination of iAUC0-12h will be calculated. After getting the iAUC0-12h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 12h is defined as 12 hours after the intake of supplement. | 0h-12h (on Day 1 and Day 15) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of iAUC of EPA+DHA from 0 to 24hours (iAUC0-24h) between two study products | Blood concentrations for EPA+DHA in plasma at 0h and 24h will be analyzed, and iAUC0-24h will be calculated. After getting the iAUC0-24h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 24h is defined as 24 hours after the intake of supplement. | 0h-24h (on Day 2 and Day 16) | 
| Comparison of iAUC EPA+DHA from 0 to 72hours (iAUC0-72h) between two study products | Blood concentrations for EPA+DHA in plasma at 0h and 72h will be analyzed, and iAUC0-72h will be calculated. After getting the iAUC0-72h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 72h is defined as 72 hours after the intake of supplement. | 0h-72h (on Day 4 and Day 18) | 
| Comparison of iAUC EPA from 0 to 12hours (iAUC0-12h) between two study products | Blood concentrations for EPA in plasma at 0h and 12h will be analyzed, and iAUC0-12h will be calculated. After getting the iAUC0-12h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 12h is defined as 12 hours after the intake of supplement. | 0h-12h (on Day 1 and Day 15) | 
| Comparison of iAUC DHA from 0 to 12hours (iAUC0-12h) between two study products | Blood concentrations for DHA in plasma at 0h and 12h will be analyzed, and iAUC0-12h will be calculated. After getting the iAUC0-12h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 12h is defined as 12 hours after the intake of supplement. | 0h-12h (on Day 1 and Day 15) | 
| Comparison of iAUC EPA from 0 to 24hours (iAUC0-24h) between two study products | Blood concentrations for EPA in plasma at 0h and 24h will be analyzed, and iAUC0-24h will be calculated. After getting the iAUC0-24h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 24h is defined as 24 hours after the intake of supplement. | 0h-24h (on Day 2 and Day 16) | 
| Comparison of iAUC DHA from 0 to 24hours (iAUC0-24h) between two study products | Blood concentrations for DHA in plasma at 0h and 24h will be analyzed, and iAUC0-24h will be calculated. After getting the iAUC0-24h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 24h is defined as 24 hours after the intake of supplement. | 0h-24h (on Day 2 and Day 16) | 
| Comparison of iAUC EPA from 0 to 72hours (iAUC0-72h) between two study products | Blood concentrations for EPA in plasma at 0h and 72h will be analyzed, and iAUC0-72h will be calculated. After getting the iAUC0-72h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 72h is defined as 72 hours after the intake of supplement. | 0h-72h (on Day 4 and Day 18) | 
| Comparison of iAUC DHA from 0 to 72hours (iAUC0-72h) between two study products | Blood concentrations for DHA in plasma at 0h and 72h will be analyzed, and iAUC0-72h will be calculated. After getting the iAUC0-72h, difference of AUC curves between groups will be calculated. The time point 0h is defined as the time when study subjects is taking the supplement, while time point 72h is defined as 72 hours after the intake of supplement. | 0h-72h (on Day 4 and Day 18) | 
| Difference on Cmax of EPA+DHA between two products | Cmax of EPA+DHA will be calculated for both products, and the difference will be compared between the products. | Day 1 and Day 15 | 
| Difference on Cmax of EPA between two products | Cmax of EPA will be calculated for both products, and the difference will be compared between the products. | Day 1 and Day 15 | 
| Difference on Cmax of DHA between two products | Cmax of DHA will be calculated for both products, and the difference will be compared between the products. | Day 1 and Day 15 | 
| Difference on Tmax of EPA+DHA between two products | Tmax of EPA+DHA will be calculated for both products, and the difference will be compared between the products. | Day 1 and Day 15 | 
| Difference on Tmax of EPA between two products | Tmax of EPA will be calculated for both products, and the difference will be compared between the products. | Day 1 and Day 15 | 
| Difference on Tmax of DHA between two products | Tmax of DHA will be calculated for both products, and the difference will be compared between the products. | Day 1 and Day 15 | 
| Difference on total omega 6 fatty acids vs total omega 3 fatty acid ratio (n-6/n-3) in plasma at 12 hours between two products | Total omega 6 fatty acids include: linoleic acid, γ-Linolenic acid, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, adrenic acid, and docosapentaenoic acid. Total omega 3 fatty acids include: α-Linolenic acid, EPA, docosapentaenoate acid and DHA. The difference on n-6/n-3 ratio will be calculated between two products. The time point 12h is defined as 12 hours after the intake of supplement. | Day 1 and Day 15 | 
| Difference on total omega 6 fatty acids vs total omega 3 fatty acid ratio (n-6/n-3) in plasma at 24 hours between two products | Total omega 6 fatty acids include: linoleic acid, γ-Linolenic acid, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, adrenic acid, and docosapentaenoic acid. Total omega 3 fatty acids include: α-Linolenic acid, EPA, docosapentaenoate acid and DHA. The difference on n-6/n-3 ratio will be calculated between two products. The time point 24h is defined as 24 hours after the intake of supplement. | Day 2 and Day 16 | 
| Difference on total omega 6 fatty acids vs total omega 3 fatty acid ratio (n-6/n-3) in plasma at 72 hours between two products | Total omega 6 fatty acids include: linoleic acid, γ-Linolenic acid, eicosadienoic acid, eicosatrienoic acid, arachidonic acid, adrenic acid, and docosapentaenoic acid. Total omega 3 fatty acids include: α-Linolenic acid, EPA, docosapentaenoate acid and DHA. The difference on n-6/n-3 ratio will be calculated between two products. The time point 72h is defined as 72 hours after the intake of supplement. | Day 4 and Day 18 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Omega 3 fatty acids, EPA, DHA