Safety and Tolerability of Krill Powder Supplement in Slightly Overweight People With Moderately Elevated Blood Pressure

Prospective, Randomized, Single-center, Double-blinded, Placebo-controlled Study on Safety and Tolerability of the Krill Powder Product in Slightly Obese Study Subjects With Moderately Elevated Blood Pressure

The aim of this study was to systematically collect data on safety and tolerability of krill powder in humans and simultaneously gain efficacy data by measuring the risk factors for cardiovascular disease.

The study was a randomised, double-blinded, placebo-controlled intervention study with slightly obese subjects with mildly or moderately elevated blood pressure. Study was conducted at two study sites in Central (Tampere) and Northern Finland (Oulu). In total 35 subjects were randomised according to randomisation list to two groups (krill powder or placebo) in a balanced manner (1:1), separately for both gender and site. Concealed allocation was used to keep both subjects and staff blinded. The study consisted of a pre-screening, Day -7-(-14) screening visit, Day 0 baseline (Randomization visit) and 8-week safety and tolerance follow-up period with three follow-up visits on Day 14, Day 28 and Day 56.

As a primary endpoint of the study, the total number of reported adverse events were compared in the study subject groups taking 8 capsules (4 g) krill oil powder or 8 capsules (4 g) of placebo for the 8-week follow-up period.

Study Overview

• Status: Completed
• Conditions: Adverse Drug Event; Side Effects of Drugs
• Intervention / Treatment: Dietary supplement: Nutritional counseling A; Dietary supplement: Nutritional counselling B

Detailed Description

Krill powder is a food supplement rich in active ingredients such as fatty acids, phospholipids, protein and antioxidants like astaxanthin. It is considered to be more effective in lowering triglyceride values than fish oils and it may have positive effect on cholesterol values as well. Krill proteins may have positive effect on blood pressure and astaxanthin has anti-oxidative and anti-inflammatory properties. Thus, krill powder has a lot of potential in improving lipid values and having other positive health effects on cardiovascular system. However, there haven't been many clinical studies done with krill powder and thus systematic data on human safety is limited.

The aim of this study was to systematically collect data on safety and tolerability of krill powder in humans and simultaneously gain efficacy data by measuring the risk factors for cardiovascular disease.

The study was a randomised, double-blinded, placebo-controlled intervention study with slightly obese subjects with mildly or moderately elevated blood pressure. Study was conducted at two study sites in Central (Tampere) and Northern Finland (Oulu). In total 35 subjects were randomised according to randomisation list to two groups (krill powder or placebo) in a balanced manner (1:1), separately for both gender and site. Concealed allocation was used to keep both subjects and staff blinded. The study consisted of a pre-screening, Day -7-(-14) screening visit, Day 0 baseline (Randomization visit) and 8-week safety and tolerance follow-up period with three follow-up visits on Day 14, Day 28 and Day 56.

A total of 6 study visits were included. At pre-screening visit the study subjects were requested to sign pre-screening visit informed consent form. A structured interview on demographics (age, sex, ethnicity), previous and current diseases, current medication, alcohol and tobacco consumption and use of dietary supplements (especially fish oil and other n-3 fatty acid (FA) supplements, plant sterols and cholesterol lowering fiber supplements (guar gum, glucomannan, oat fiber etc.) and use of fish foods was carried out at the screening visit and replicated at the day 56 visit. Study included one test product: krill powder derived from antarctic krill (Euphausia Superba) (Rimfrost Pristine®, Rimfrost AS, PO box 234, 6099 Fosnavaag, Norway) and placebo product and both were given in capsule form, 4 capsules in the morning and 4 in the evening.

Nutritional counselling regarding the consumption of fish, omega-3 and -6 fatty acids, food supplements and investigational product for the duration of the study were given for the study subjects at the screening visit by a study nurse or registered dietitian and compliance was followed throughout the study. The subjects were advised to keep their medication, lifestyle, background diet and body weight constant during the study and deviation were recorded into the diary.

As a primary endpoint of the study, the total number of reported adverse events were compared in the study subject groups taking 8 capsules (4 g) krill oil powder or 8 capsules (4 g) of placebo for the 8-week follow-up period. Any unfavourable and unintended sign, symptom or medical complaint and worsening of a pre-existing condition was regarded as adverse event (AE). Study subjects kept diary for the whole duration of the study and were requested to write down all unfavourable symptoms and medical complaints not existing at baseline or significantly worsened from baseline situation. Completeness of diaries was checked at each study visit. All reported adverse events were recorded, coded and analysed carefully to determine severity, possible relation to study products, onset and outcome of the event. In addition, safety laboratory values, cholesterol and triglyceride values and blood pressure was measured.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Finland
  • Kuopio, Finland, 70701
    • Oy Medfiles Ltd

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 18-65 years
• Slightly obese female and male subjects (BMI between 25-30 kg/ m2)
• Mildly or moderately elevated blood pressure (RR systolic 130-159/ diastolic under 99)
• Signed written informed consent

Exclusion Criteria:

• Medication potential to affect serum lipids (lipid-lowering drugs)
• Familial hypercholesterolemia, marked combined hyperlipidemia, condition that would impair fat absorption (e.g. chronic pancreatitis, pancreatic lipase deficiency syndrome)
• Any untreated medical condition affecting absorption of fat
• Type 1 and 2 diabetes
• Cancer or other malignant disease within the past five years
• Periodical hormone replacement therapy
• High intake of oily fish (>2 times per week as a principal meal) (i.e. salmon, herring, sardines, mackerel, vendace)
• Smoking
• Alcohol consumption >15 doses per week
• Pregnant, lactating or wish to become pregnant
• Hypersensitivity to fish or any of the components of the test products
• Regular use (> 3 times per week) of n-3 or other fatty acid supplements, plant sterols or fiber supplements 4 weeks before randomization
• Lack of suitability for participation in the trial, for any medical reason, as judged by the PI

Study Plan

How is the study designed?

Design Details

• Primary Purpose: OTHER
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Krill oil; Krill powder capsules, 4 g	Dietary supplement: Nutritional counseling A; Krill powder capsules
PLACEBO_COMPARATOR: Placebo; Placebo capsules, maize strach, 4 g	Dietary supplement: Nutritional counselling B; Placebo capsules

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Adverse events	Total number of reported adverse events	Screening, baseline, day 28, day 56

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Type of adverse event	Coding by MedDRA and reported with System organ class (SOC) and Prefered term (PT) levels, seriousness, severity, onset and causality of the reported adverse events	Screening, baseline, day 28, day 56
Change in Systolic blood pressure	Mean and mean change (0 vs 8 wk) in systolic blood pressure recorded with 1 mmHg accuracy taken in the screening and during the intervention visits (three measurements are taken altogether and an average of last two measures is used in the analysis)	Screening, baseline, day 28, day 56
Change in Diastolic blood pressure	Mean and mean change (0 vs 8 wk) in diastolic blood pressure recorded with 1 mmHg accuracy taken in the screening and during the intervention visits (three measurements are taken altogether and an average of last two measures is used in the analysis)	Screening, baseline, day 28, day 56
Change in thyrotropin	Regular safety parameters from the blood including mean and median variables of blood thyrotropin	Screening, baseline, day 28, day 56
Change in Alanine transaminase (ALT)	Regular safety parameters from the blood including mean and median variables of blood Alanine transaminase (ALAT)	Screening, baseline, day 28, day 56
Change in Aspartate transaminase (AST)	Regular safety parameters from the blood including mean and median variables of blood Aspartate transaminase (ASAT)	Screening, baseline, day 28, day 56
Change in blood glucose	Regular safety parameters from the blood including mean and median variables of blood glucose	Screening, baseline, day 28, day 56
Change in gamma glutamyl transferase	Regular safety parameters from the blood including mean and median variables of gamma glutamyl transferase	Screening, baseline, day 28, day 56
Change in creatinine	Regular safety parameters from the blood including mean and median variables of creatinine	Screening, baseline, day 28, day 56
Change in blood count	Regular safety parameters from the blood including mean and median variables of blood count	Screening, baseline, day 28, day 56
Change in Thyroid stimulating hormone (TSH)	Regular safety parameters from the blood including mean and median variables of Thyroid stimulating hormone (TSH)	Screening, baseline, day 28, day 56
Change in Triglycerides	Mean concentration of serum total triglycerides and mean change (0 vs 8 wk) in serum total and lipoprotein lipids	Screening, baseline, day 28, day 56
Change in total cholesterol	Mean concentration of total cholesterol during the 8-week intervention and mean change (0 vs 8 wk) in serum total and lipoprotein lipids	Screening, baseline, day 28, day 56
Change in Low density lipoproteine (LDL)-cholesterol	Mean concentration of serum LDL-cholesterol during the 8-week intervention and mean change (0 vs 8 wk) in serum total and lipoprotein lipids	Screening, baseline, day 28, day 56
Change in High density lipoproteine (HDL)-cholesterol	Mean concentration of serum HDL-cholesterol during the 8-week intervention and mean change (0 vs 8 wk) in serum total and lipoprotein lipids	Screening, baseline, day 28, day 56

Collaborators and Investigators

• Sponsor: Olympic Seafood AS

Publications and helpful links

General Publications

• Sarkkinen ES, Savolainen MJ, Taurio J, Marvola T, Bruheim I. Prospective, randomized, double-blinded, placebo-controlled study on safety and tolerability of the krill powder product in overweight subjects with moderately elevated blood pressure. Lipids Health Dis. 2018 Dec 20;17(1):287. doi: 10.1186/s12944-018-0935-x.

Study record dates

Study Major Dates

• Study Start (ACTUAL): October 6, 2015
• Primary Completion (ACTUAL): June 17, 2016
• Study Completion (ACTUAL): June 17, 2016

Study Registration Dates

• First Submitted: March 27, 2017
• First Submitted That Met QC Criteria: April 7, 2017
• First Posted (ACTUAL): April 13, 2017

Study Record Updates

• Last Update Posted (ACTUAL): April 13, 2017
• Last Update Submitted That Met QC Criteria: April 7, 2017
• Last Verified: April 1, 2017

More Information

Terms related to this study

• Keywords: tolerability; safety; omega-3 fatty acids; eicosapentaenoic acid; docosahexaenoic acid; krill oil; adverse event; krill powder
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Cardiovascular Diseases; Vascular Diseases; Hypertension; Drug-Related Side Effects and Adverse Reactions
• Other Study ID Numbers: OP001

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No