Clinical trial NCT02865044: Study to Evaluate the Acute Bioavailability of EPA and DHA From a DietarySupplement in Healthy Men and Women
Official title: A Randomized, Controlled, Crossover Study to Evaluate the Acute Bioavailability of Eicosapentaenoic Acid andDocosahexaenoic Acid From a DietarySupplement in Healthy Men and Women: A 72-Hour Study With Controlled Feeding
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Healthy
Keywords: Fatty Acids
Fish Oil
Marine Copepod
Fatty Acid Absorption
Lead sponsor: Calanus
Sponsor class: INDUSTRY
Collaborators: name: Biofortis Clinical Research, Inc.
First posted: 2016-08-12
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Maximum age (years): 59
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Eligibility criteria: 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).

Primary outcomes:
measure: Incremental area under the curve (iAUC) for plasma EPA+DHA
timeFrame: pre-product consumption (t = -0.5 h) to 72 h (iAUC-0.5-72h)
Secondary outcomes:
measure: Maximum plasma concentration (Cmax) and time to Cmax (Tmax) for EPA, DHA, and EPA+DHA
timeFrame: pre-product consumption (t = -0.5 h) to 72 h
measure: iAUCs for plasma EPA+DHA
timeFrame: pre-product consumption (t = -0.5 h) to 24 h (iAUC-0.5-24 h), and to 48 h (iAUC-0.5-48 h)
measure: The iAUCs for plasma EPA and DHA alone
timeFrame: (iAUC-0.5-24 h, iAUC-0.5-48 h, iAUC-0.5-72 h).
Other outcomes:
Locations:
city: Addison
country: United States
facility: Biofortis Clinical Research
state: Illinois
Study officials:
affiliation: Biofortis Clinical Research, Inc.
name: Chad Cook, PhD
role: STUDY_DIRECTOR
References: