Effects of Cetoleic Acid on Atherosclerosis (Ketolinsyre's Effekt på Aterosklerose)

Study Overview
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Brief Summary
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In this Randomized Controlled Trial (RCT) we want to study the effect of an oil with high concentrations of cetoelic acid (C22:n1-11) (intervention) compared to supplements with a low concentration of cetoleic acid (control), but with equivalent content of EPA og DHA, on plasma levels of epa and dha as well as atherosclerotic markers, glucose, c-peptide and triglycerides in a patient group with a metabolically unfavorable phenotype. Our primary endpoints are changes in the concentration of EPA and DHA in plasma.

Detailed Description
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This is a randomized double-blinded controlled trial (randomized 1:1). Study population: men and women 20-70 years with a metabolically unfavorable phenotype defined as: triglycerides > 1.7 mmol/L and waist measurement > 80 cm (women) and > 94 cm (men). Study design: 3 weeks run-in-period where all participants consume control capsules every morning. Randomization intervention: control (1:1). All participants consume their capsules (control or intervention) for 4 weeks. The intervention oil is consists of an oil high in cetoleic acid and the control oil is low in cetoleic acid. Both the intervention oil and the control oil are a mix of different oils; fish oils, olive oil, high-oleic sunflower oil and rapeseed oil so that the content of EPA, DHA and ALA is similar in the two oils. Power calculation and sample size: It was expected a difference of 15% in n-3 between the groups after the intervention (Østbye et al. 2019, doi:10.1017/S0007114519001478). The level of significance was set to 5% (two-sided) and the power to 80%. A total of thirty-eight subjects were required to participate in the study, but a high dropout rate was expected (20%) and it was considered necessary to include a total of seventy (n=70) subjects (thirty-five per arm).

Official Title
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Effects of Ketolic Acid on Atherosclerosis Markers in High-risk Patients With Metabolic Syndrome (Effekt av Ketolinsyre på aterosklerosemarkører i høyrisikopasienter Med Metabolsk Syndrom)

Conditions
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Metabolic Syndrome

Intervention / Treatment
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* Dietary Supplement: Cetoleic acid
* Dietary Supplement: Control oil


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Triglycerides > 1.7 mmol/L Waist measurement > 80 cm (women) and > 94 cm (men) Exclusion Criteria: Chronic disease (liver/kidney/metabolism) Ongoing active cancer treatment Excessive alcohol consumption (>40g/day) Pregnant/breastfeeding or planned pregnancy during the intervention High intake of fish (>3 weekly meals) Level of free thyroxine (T4) and triiodothyronine (T3) outside reference ranges. Hypertension (≥ 160/ 100 mmHg) Total cholesterol > 7.8 mmol/L Blood donation during the intervention period Difficulty following the protocol Smoking or sniffing Regular use (> 1 day/week) of anti-inflammatory drugs Regular use of omega-3 supplements/cod liver oil Drug use other than stable use of statins, hypertension drugs (Ca antagonists, diuretics and beta blockers). Hormonal treatment excluding stable use of thyroxine and birth control pills/contraceptive rod

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized double-blinded controlled trial (Randomized 1:1, control:intervention). Run-in period of 3 weeks where all participants receive the control capsules.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention (Cetoleic acid)<br>6 x capsules intervention oil (oil = mix of fish oils, olive oil, high-oleic sunflower oil and rapeseed oil) with high content of cetoleic acid (1780 mg/day, estimated: 29,76%) every morning for 4 weeks. | Dietary Supplement: Cetoleic acid<br>* Very long monounsaturated fatty acid (C22:1n-11)<br>|
| Placebo Comparator: Control oil<br>6 x capsules control oil (oil= mix of fish oils, olive oil, high-oleic sunflower oil and rapeseed oil) with low content of cetoleic acid (35 mg/day, estimated 0.58%) every morning for 4 weeks. | Dietary Supplement: Control oil<br>* Mix of oils with low cetoleic acid content<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| EPA and DHA in plasma | EPA and DHA concentration in plasma measured at baseline and after 4 week intervention (and as a control measurement at the screening visit) | 4 weeks intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Lipid profile | Plasma levels of triglycerides, total cholesterol, LDL cholesterol, HDL cholesterol, apolipoproteins (apoB and apoA), and Lp(a) | 4 weeks intervention | 
| Glucose | Serum levels of glucose | 4 weeks intervention | 
| Inflammatory markers | The concentration of circulating levels of inflammatory markers | 4 weeks intervention | 
| Gene expression, metabolome and lipidome | Changes in PBMC (peripheral blood mononuclear cell) gene expression profile. Changes in plasma metabolome and lipidome profile. Changes in PBMC epitranscriptome, as a regulator of the gene expression profile | 4 weeks intervention | 
| Resolvin | Blood levels of resolvin (omega- 3 derivates) concentration | 4 weeks intervention | 
| C-peptid | serum levels of C-peptid | 4 weeks intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Omega 3 fatty acids, Sustainability, Cetoleic acid, Very long monounsaturated fatty acid, Cardiovascular disease prevention, Antiinflammation