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MaxSimil and Vitamin K2: Determining Their Bioavailability

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ClinicalTrials.gov Identifier: NCT03897660
Recruitment Status : Recruiting
First Posted : April 1, 2019
Last Update Posted : April 1, 2019
Sponsor:
Collaborator:
Samuel Fortin, SFC pharma and associate professor UQAR
Information provided by (Responsible Party):
Mélanie Plourde, Université de Sherbrooke

Brief Summary:

The benefits of a diet enriched with omega-3 fatty acids are multiple and confirmed by several clinical studies. Supplementation with vitamin K, a fat-soluble vitamin, can increase or maintain bone density in postmenopausal women and reduce the risk of fracture. In addition, some studies show that vitamin K may promote the absorption of omega-3 fatty acids. Fish oil, rich in omega-3, is one of the world's favorite forms of omega-3 supplements. However, many people suffer from gastrointestinal discomfort when ingesting fish oil capsules. To minimize these discomforts and improve plasmatic omega-3 bioavailability, Neptune Wellness Solutions has developed a patented formulation of fish oil called MaxSimil®, where omega-3s are in the monoglyceride (MAG) form, a predigested omega-3 form. This formulation has been tested in humans in a double-blind controlled-randomized pharmacokinetic (PK) pilot study with crossover design. PK is defined as a monitoring of omega-3 levels in the blood by frequent blood sampling over a period of 24 hours following the ingestion of a single dose of omega-3. The results obtained showed that MaxSimil® omega-3s are 3 times more absorbed in the blood than the comparison formulation, a source of omega-3 in the ethyl ester (EE) form.

Although this first study confirms a greater bioavailability of MaxSimil®, a complementary PK study is necessary to confirm these results and to correct an important methodological bias. In fact, the pilot study did not include a comparator group where omega-3s were in the triglyceride (TG) form, the most widely omega-3 form currently consumed, but rather use an EE form, which have lower bioavailability than TG form. This may therefore have biased the study from the point of view of the comparator and thus give the impression that the comparator had been deliberately chosen to be less bioavailable than the MaxSimil®.

In order to confirm the superiority of MaxSimil® (omega-3 MAG form), both in terms of bioavailability and incidence of side effects, the aim of this study is to redo a PK study using this time two comparators, the two main forms of omega-3 currently used (TG and EE forms), as well as a supplementation with vitamin K2 (a form of vitamin K). Our hypothesis is that MaxSimil® will be associated with a better omega-3 bioavailability and a lower incidence of side effects than the other two forms (TG and EE), and possibly also with a better vitamin K bioavailability.


Condition or disease Intervention/treatment Phase
Healthy Dietary Supplement: Omega-3 + vitamin K2 (TG form of omega-3) Dietary Supplement: Omega-3 + vitamin K2 (EE form of omega-3) Dietary Supplement: Omega-3 + vitamin K2 [MaxSimil (MAG form of omega-3)] Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: Double-blind controlled-randomized pharmacokinetic (PK) pilot study with crossover design (10 men and 10 women), with a minimum of 6 days between treatments
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description: Neither the participant nor the research nurse will know the administration order of the different treatments administered. All plasma samples collected during the research project will be anonymized i.e. it will not be possible to identify the participant by his name since a number will be assigned to him. The code key linking the participant's name to his number will be stored, with access restricted to those designated by the principal investigator. The data file is also protected by a password.
Primary Purpose: Treatment
Official Title: Pharmacokinetics of a Combination of Omega-3 Fatty Acids and Vitamin K2 as a Natural Product
Actual Study Start Date : March 29, 2019
Estimated Primary Completion Date : December 1, 2019
Estimated Study Completion Date : March 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Vitamin K

Arm Intervention/treatment
Active Comparator: TG form of omega-3
The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive the omega-3 fatty acidsesterified in a reconstitute triglyceride form as a unique dose of 1.5 g EPA + DHA in TG form + 45 mg vitamin K2.The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.
Dietary Supplement: Omega-3 + vitamin K2 (TG form of omega-3)

The intervention is a randomized double bond cross over design testing the pharmacokinetics of a monoglyceride formulation compared to a triglyceride and an ethyl ester form.

Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform all three treatments, with a minimum of 6 days between treatments. A questionnaire will document the side effects felt by participants during the omega-3 supplement taking day.


Active Comparator: EE form of omega-3
The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive the omega-3 fatty acids in ethyl esters form as a unique dose of 1.5 g EPA + DHA in TG form + 45 mg vitamin K2.The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.
Dietary Supplement: Omega-3 + vitamin K2 (EE form of omega-3)

The intervention is a randomized double bond cross over design testing the pharmacokinetics of a monoglyceride formulation compared to a triglyceride and an ethyl ester form.

Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform all three treatments, with a minimum of 6 days between treatments. A questionnaire will document the side effects felt by participants during the omega-3 supplement taking day.


Experimental: MaxSimil (MAG form of omega-3)
The participant will arrive fasted at he research center. After installing a cathether and drawing 5 mL of blood, the participants will be given one of the active comparator or the treatment. The choice of the treatment/comparator will be random. In this arm, the participant will receive the omega-3 fatty acids in MaxSimil® form as a unique dose of 1.5 g EPA + DHA in TG form + 45 mg vitamin K2.The participant will consume this unique dose with a standardized breakfast. There will thereafter be blood sample collection over 24 h to evaluate the level of omega-3 fatty acids in the plasma and a side effect questionnaire will be administered to monitor side effects.
Dietary Supplement: Omega-3 + vitamin K2 [MaxSimil (MAG form of omega-3)]

The intervention is a randomized double blind cross over design testing the pharmacokinetics of a monoglyceride formulation compared to a triglyceride and an ethyl ester form.

Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. Blood samples will be collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours. Each participant will perform all three treatments, with a minimum of 6 days between treatments. At each blood draw time points, a questionnaire will be administered to the particpant to monitor if they experiencec side effects with the dietary supplement they ingested in the morning.





Primary Outcome Measures :
  1. Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the area under the curve (AUC) 0-24h as the first parameter of the PK [ Time Frame: Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment. ]
    Plasma omega-3 (DHA and EPA) levels will be measured by gas phase chromatography while plasma vitamin K2 level will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, area under the curve (AUC) 0-24 hours will be calculated, as the first parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

  2. Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the AUC 0-6h (absorption study) as the second parameter of the PK [ Time Frame: Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment. ]
    Plasma Omega-3 (DHA and EPA) will be measured by gas phase chromatography while plasma vitamin K2 will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, AUC 0-6 hours (absorption study) will be calculated, as the second parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

  3. Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the maximum concentration as the third parameter of the PK [ Time Frame: Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment. ]
    Plasma Omega-3 (DHA and EPA) will be measured by gas phase chromatography while plasma vitamin K2 will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, maximum concentration will be calculated, as the third parameter of the PK. Statistical analyzes will then be performed on this PK parameter.

  4. Determine the bioavailability of omega-3 and vitamin K2 according to the forms ethyl ester (EE), triglycerides (TG) and MaxSimil® (monoglycerides, MAG): Calculating the time when the maximum concentration is reached, as the fourth parameter of the PK [ Time Frame: Treatments are randomly assigned on days 0, 7 and 14 of the clinical study. GC and HPLC analyzes will be measured on plasma from blood samples collected at time 0, 1, 2, 4, 5, 6, 8, 9, 10, 12 and 24 hours post-treatment. ]
    Plasma Omega-3 (DHA and EPA) will be measured by gas phase chromatography while plasma vitamin K2 will be measured by high-performance liquid chromatography (HPLC), each being performed randomly blindly. After GC and HPLC analyzes, time when the maximum concentration is reached will be calculated, as the fourth parameter of the PK. Statistical analyzes will then be performed on this PK parameter.


Secondary Outcome Measures :
  1. To determine the incidence of side effects (including gastrointestinal discomfort) of these same three forms of omega-3 fatty acid supplements [ Time Frame: A questionnaire will document the side effects felt by participants during the omega-3 supplement taking day. ]
    The side effects of EPA + DHA type omega-3 supplements, all mild, belong to the category of gastrointestinal discomfort. These include dysgeusia (fishy taste or taste alteration), belching and nausea. A questionnaire will document the side effects felt by participants during the omega-3 supplement taking day. Statistical analyzes will then be performed on the evaluation of side effects (including gastrointestinal discomfort) by questionnaire.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Male or female aged 18-65 years (inclusive)
  • Body mass index between 18.5 and 29.9 kg / m² (inclusive) at the pre-selection visit
  • Normal to moderately elevated lipidemia (total cholesterol ≤ 240 mg / dl, LDL ≤ 160 mg / dl, TG ≤ 199 mg / dl)
  • Women of childbearing potential should use an approved method of contraception for the duration of the study so that they do not become pregnant during the study

Exclusion Criteria:

  • Menopause or pre-menopause with amenorrhea> 6 months
  • Tobacco
  • Malnutrition (assessed by albumin, hemoglobin and blood lipid levels)
  • DHA plasma levels greater than 3% or people consuming omega-3 fatty acid supplements for more than one month
  • History of current or past alcohol and / or drug abuse
  • Parkinson's disease
  • Down syndrome
  • Cardiac event or recent major surgery (6 months)
  • Current or past performance athlete
  • Systemic disease: vasculitis, Systemic Lupus Erythematosus (SLE), sarcoidosis, cancer (unless in remission for more than 5 years and without cerebral involvement), uncompensated hypothyroidism (unless stabilized on treatment for more than 3 months), vitamin deficiency B12 not supplemented and / or complicated (unless stabilized on treatment for more than 3 months), diabetes, severe renal insufficiency
  • Abnormal blood pressure and / or liver, renal or thyroid function; these conditions will not exclude a patient if he has been stabilized on treatment for at least 3 months and there has been no recent change in the medication.
  • Known psychiatric history: schizophrenia, psychotic disorders, major affective disorders (bipolar disorder and major depression <5 years), panic disorder, Obsessive Compulsive Disorder (OCD)
  • Epilepsy, cerebral trauma with loss of consciousness, subarachnoid hemorrhage
  • Not available to perform the 3 different treatments
  • Medication affecting fat absorption (i.e., Orlistat, Alli, etc.), which interferes with omega-3 fatty acids uptake (i.e., anticoagulants) or which affects lipid metabolism (i.e., all types of drug for decrease cholesterol or triglycerides)
  • Nobody under a special diet like a fat-free, vegetarian or vegan diet
  • People who have a malabsorption disease such as pancreatitis, Crohn's disease or who have had bariatric surgery.
  • Allergy to fish or seafood
  • Pregnant women or nursing women
  • Person who donated blood or had significant blood loss in the 30 days prior to study start

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03897660


Contacts
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Contact: Mélanie Plourde, PhD 819-780-2220 ext 45664 melanie.plourde2@usherbrooke.ca

Locations
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Canada, Quebec
Melanie Plourde Recruiting
Sherbrooke, Quebec, Canada, J1H4C4
Contact: Melanie Plourde, PhD    819-780-2220 ext 45664    melanie.plourde2@usherbrooke.ca   
Sponsors and Collaborators
Université de Sherbrooke
Samuel Fortin, SFC pharma and associate professor UQAR
Investigators
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Principal Investigator: Mélanie Plourde, PhD Université de Sherbrooke

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Responsible Party: Mélanie Plourde, Associate professor, Department of medicine, Geriatric service, Université de Sherbrooke
ClinicalTrials.gov Identifier: NCT03897660     History of Changes
Other Study ID Numbers: MaxSimil and vitamin K2
First Posted: April 1, 2019    Key Record Dates
Last Update Posted: April 1, 2019
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: We do not plan to share individual participant data to other researchers

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Mélanie Plourde, Université de Sherbrooke:
Omega-3 fatty acids
Vitamin K2
Bioavailability
Side effects
Monoacylglyderols
Additional relevant MeSH terms:
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Vitamins
Vitamin K
Vitamin K 2
Vitamin MK 7
Micronutrients
Nutrients
Growth Substances
Physiological Effects of Drugs
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants