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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Adverse Drug Event, Side Effects of Drugs

Intervention / Treatment
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* Dietary Supplement: Nutritional counseling A
* Dietary Supplement: Nutritional counselling B


Participation Criteria
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Eligibility Criteria
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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

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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two parallel groups (placebo and Krill oil), intervention trial (56 days)
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Krill oil<br>Krill powder capsules, 4 g | Dietary Supplement: Nutritional counseling A<br>* Krill powder capsules<br>|
| Placebo Comparator: Placebo<br>Placebo capsules, maize strach, 4 g | Dietary Supplement: Nutritional counselling B<br>* Placebo capsules<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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krill powder, krill oil, safety, tolerability, adverse event, omega-3 fatty acids, eicosapentaenoic acid, docosahexaenoic acid