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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Metabolic Syndrome
• Intervention / Treatment: Dietary supplement: Cetoleic acid; Dietary supplement: Control oil

Detailed Description

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).

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kirsten B. Holven, PhD; Phone Number: +4722851361; Email: kirsten.holven@medisin.uio.no
• Study Contact Backup: Name: Iselin S. Holen, MSc; Phone Number: +4722894882; Email: ishole@ous-hf.no

Study Locations

• Norway
  • Oslo, Norway
    • Recruiting
    • Oslo University Hospital
    • Contact: Kirsten B Holven, Professor

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention (Cetoleic acid); 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; Very long monounsaturated fatty acid (C22:1n-11)
Placebo Comparator: Control oil; 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; Mix of oils with low cetoleic acid content

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Oslo University Hospital
• Collaborators: University of Oslo
• Investigators: Principal Investigator: Kirsten B. Holven, PhD, Oslo University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): January 3, 2024
• Primary Completion (Estimated): August 30, 2024
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: December 6, 2023
• First Posted (Actual): December 15, 2023

Study Record Updates

• Last Update Posted (Actual): January 5, 2024
• Last Update Submitted That Met QC Criteria: January 3, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Omega 3 fatty acids; Sustainability; Cardiovascular disease prevention; Cetoleic acid; Very long monounsaturated fatty acid; Antiinflammation
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Disease; Insulin Resistance; Hyperinsulinism; Syndrome; Metabolic Syndrome; Atherosclerosis
• Other Study ID Numbers: 605236

Drug and device information, study documents

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