Study to Evaluate the Acute Bioavailability of EPA and DHA From a DietarySupplement in Healthy Men and Women

Not Applicable

Completed

• Conditions: Healthy
• Interventions: Other: Ethyl Ester Marine Oil; Other: Wax Ester Marine Oil

• Registration Number: NCT02865044
• Lead Sponsor: Calanus

Brief Summary

The objective of this study was to evaluate and compare the acute bioavailability of EPA and DHA in wax ester form provided as a dietary supplement compared to a well-studied and defined ethyl ester formulation in generally healthy men and women.

Detailed Description

A randomized, controlled two-period crossover study included one screening/baseline visit (visit 1, day -7) with four test visits during Period I (visits 2, 3, 4, and 5; days 0, 1, 2, and 3) and four tests visits during Period II (visits 6, 7, 8, and 9; days 14, 15, 16, and 17) with at least a 7-d washout between test periods. Eighteen healthy adults with fasting TAG concentrations \<200 mg/dL were randomly assigned to one of two treatment sequences: receive 8 capsules containing Calanus oil® (Calanus AS, Tromso, Norway) supplying a total of 4 g of oil providing 260 mg EPA and 156 mg/day DHA primarily as wax esters, followed by 1 capsule supplying 1 g of oil providing 465 mg EPA and 375 mg DHA as ethyl esters (Lovaza®, GlaxoSmithKline, Research Triangle Park, NC); or, to receive Lovaza followed by Calanus Oil. Product was dispensed in-clinic with an standardized EPA- and DHA- free breakfast meal (t=0). Blood samples were obtained in-clinic at t= -30 min, and 1, 2, 4, 6, 8, 10 and 12 h timepoints. Subjects were provided a standardized EPA- and DHA-free meal at t=4 h and t=8. Subject were dismissed from the clinic after t-12 h blood draw and returned the morning of days 1, 2 and 3 (days 15, 16 and 17) for a 24 h, 48 h and 72 h fasting blood draw.

Study Timeline

• Study Start: 2015-03
• Primary Completion: 2015-04
• Study Completion: 2015-04
• Status Verified: 2016-08
• Study First Submitted: 2016-08-09
• Study First Submitted QC: 2016-08-11
• Last Update Submitted: 2016-08-11
• Study First Posted: 2016-08-12
• Last Update Posted: 2016-08-12

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

1. Male or female, 18-59 years of age, inclusive.
2. BMI of ≥18.50 and ≤29.99 kg/m2 at visit 1 (day -7).
3. Fasting TG <200 mg/dL at visit 1 (day -7).
4. Score of 7 to 10 on the Vein Access Scale at visit 1 (day -7).
5. No health conditions that would prevent the subject from fulfilling the study requirements as judged by the Investigator on the basis of medical history and routine laboratory test results.
6. Willing to refrain from consumption of all fish/seafood (including shellfish), and/or EPA- or DHA-containing foods and supplements 14 d prior to visit 2 (day 0) and throughout the study.
7. Willing to limit alcohol consumption to no more than 1 drink/d following visit 1 (day -7) and throughout the study.
8. Non-smoker with no plans to change smoking habits during the study period.
9. Willing to maintain habitual diet (with the exception of foods to be restricted), physical activity patterns, and body weight throughout the trial.
10. Understood the study procedures and signed forms providing informed consent to participate in the study and authorizes the release of relevant protected health information to the study Investigator.

Exclusion Criteria

1. Abnormal laboratory test results of clinical significance at visit 1 (day -7), at the discretion of the Investigator. One re-test was allowed on a separate day prior to visit 2 (day 0) for subjects with abnormal laboratory test results.
2. History or presence of clinically important endocrine (including type 1 or 2 diabetes mellitus), cardiovascular (including, but not limited to history of myocardial infarction, peripheral arterial disease, stroke), pulmonary (including uncontrolled asthma), hepatic, renal, hematologic, immunologic, dermatologic, neurologic, psychiatric or biliary disorders.
3. History or presence of a GI disorder that, in the judgment of the Investigator, may have disrupted normal digestion and absorption of the study products.
4. History of difficulty swallowing tablets/capsules that could have affected ability to consume the study products.
5. Extreme dietary habits (e.g., Atkins diet, very high protein, vegetarian), in the opinion of the Investigator.
6. Uncontrolled hypertension (systolic blood pressure ≥160 mm Hg or diastolic blood pressure ≥100 mm Hg) as defined by the blood pressure measured at visit 1 (day -7). One re-test was allowed on a separate day prior to visit 2 (day 0), for subjects whose blood pressure exceeded either of these cut points, in the judgment of the Investigator.
7. History or presence of cancer in the prior two years, except for non-melanoma skin cancer.
8. Weight loss or gain >4.5 kg in the 3 months prior to visit 1 (day -7).
9. Use of medications or dietary supplements known to alter lipid concentrations within 4 weeks of visit 1 (day -7). Dietary supplements included, but were not limited to, the following: sterol/stanol products; dietary fiber supplements (including >1 teaspoon Metamucil® or viscous fiber-containing supplement per day); red rice yeast supplements; garlic supplements; soy isoflavone supplements; or niacin or its analogues at dosages >50 mg/day (or others at the discretion of the Investigator).
10. Use of non-study related omega-3-acid ethyl ester drug(s) or dietary supplement(s) with ≥1.0 g/d of EPA, DHA, or a combination of EPA and DHA within 4 months of visit 1 (day -7).
11. Known allergy or sensitivity to omega-3 fatty acids, fish, other seafood, or any ingredient in the study product or study meals.
12. Active infection or use of antibiotics within 5 d of visits 2 and 6 (days 0 and 14). Subjects that had an active infection and/or were using antibiotics were required to wait at least 5 d after the infection resolved or antibiotic use was complete prior to the first day of each test period (visits 2 and 6, days 0 and 14).
13. Female who was pregnant, planning to be pregnant during the study period, lactating, or was of childbearing potential and unwilling to commit to the use of a medically approved form of contraception throughout the study period. The method of contraception was recorded in the source documentation.
14. Exposure to any non-registered drug product within 30 d prior to visit 1 (day -7).
15. Recent history of (within 12 months of screening; visit 1, day -7) or strong potential for alcohol or substance abuse. Alcohol abuse defined as >14 drinks per week (1 drink = 12 oz beer, 5 oz wine, or 1½ oz distilled spirits).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Ethyl Ester Marine Oil	Ethyl Ester Marine Oil	Control: Ethyl ester (EE) marine oil (Lovaza OM3 EE; 1 g providing 465 mg EPA and 375 mg DHA; 1 capsule)
Wax Ester Marine Oil	Wax Ester Marine Oil	Active: Wax ester marine oil (Calanus oil; 4 g providing 260 mg EPA and 156 mg DHA; 8 capsules)

Primary Outcome Measures

Name	Time	Method
Incremental area under the curve (iAUC) for plasma EPA+DHA	pre-product consumption (t = -0.5 h) to 72 h (iAUC-0.5-72h)

Secondary Outcome Measures

Name	Time	Method
iAUCs for plasma EPA+DHA	pre-product consumption (t = -0.5 h) to 24 h (iAUC-0.5-24 h), and to 48 h (iAUC-0.5-48 h)
Maximum plasma concentration (Cmax) and time to Cmax (Tmax) for EPA, DHA, and EPA+DHA	pre-product consumption (t = -0.5 h) to 72 h
The iAUCs for plasma EPA and DHA alone	(iAUC-0.5-24 h, iAUC-0.5-48 h, iAUC-0.5-72 h).

Trial Locations

Locations (1)

Biofortis Clinical Research; 🇺🇸 Addison, Illinois, United States