Health Effects of Cetoleic Acid (A Randomized Double Blinded Controlled Trial)

• ClinicalTrials.gov Identifier: NCT04841044
• Recruitment Status: Enrolling by invitation
• First Posted: April 12, 2021
• Last Update Posted: October 4, 2021
• Sponsor: University of Oslo
• Collaborator: Oslo University Hospital
• Information provided by (Responsible Party): Kirsten Holven, University of Oslo

Study Description

Brief Summary:

In this Randomized Controlled Trial (RCT) we want to study how supplements of cetoleic acid ( C22:n1-11) (intervention) affect the conversion of alpha-linolenic acid (ALA) to EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) in healthy subjects, compared to supplements with a low concentration of cetoleic acid (control).

Our primary endpoints are changes in the concentration of EPA and DHA in plasma and red blood cells.

Condition or disease	Intervention/treatment	Phase
Healthy Diet	Dietary Supplement: Cetoleic acid; Dietary Supplement: Control Oil	Not Applicable

Detailed Description:

This is a randomized double-blinded controlled trial ( randomized 1:1). Study population: healthy men and women 20-70 years, BMI 20-35 kg/m2.

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 consists of a fish oil high in cetoleic acid and the control oil is a mix of different oils and low in cetoleic acid.

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 60 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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 (Participant, Care Provider, Investigator)

Masking Description

All participant, the major investigator, study coordinator and the study staff are blinded for the randomizing. The capsules and capsule containers will only be identifiable by the ID (identifying) numbers on the containers.

Allocation of participants to the specific intervention group is carried out by a statistician and one person not involved in conducting the study.

• Primary Purpose: Prevention
• Official Title: Health Effects of Cetoleic Acid (Helseeffekter av Ketolinsyre)
• Actual Study Start Date: April 27, 2021
• Estimated Primary Completion Date: April 30, 2022
• Estimated Study Completion Date: December 31, 2025

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention ( Cetoleic acid); 6x mackerel oil (cetoleic acid: 16A%, estimated: 135 mg/g (FFA)) capsules every morning for 4 weeks (A%= area percent)	Dietary Supplement: Cetoleic acid; Very long monounsaturated fatty acid ( C22:1n-11)
Placebo Comparator: Control oil; 6x capsules control oil (Control oil= mix of anchovy oil, olive oil, high-oleic sunflower oil, rapeseed oil (cetoleic acid: 0,7 A% estimated: 6 mg/g (FFA)) every morning for 4 weeks (A%= area percent)	Dietary Supplement: Control Oil; Control oil consisting of: mix of anchovy oil, olive oil, high-oleic sunflower oil and rapeseed oil

Outcome Measures

Primary Outcome Measures :

1. EPA and DHA in plasma [ Time Frame: 4 weeks intervention ]
   EPA and DHA concentration in plasma measured at baseline and and after 4 week intervention (and as a "control measurement" at the screening visit)
2. EPA and DHA in red blood cells [ Time Frame: 4 weeks ]
   EPA and DHA concentration and omega 3 index (EPA+DHA/total fatty acids) in red blood cells measured at baseline and and after 4 week intervention (and as a "control measurement" at the screening visit)

Secondary Outcome Measures :

1. Lipid profile- Triglycerides [ Time Frame: 4 weeks ]
   Plasma levels of triglycerides measured at baseline and after 4 weeks intervention (and as a "control measurement" at the screening visit)
2. Lipid profile- Cholesterol [ Time Frame: 4 weeks ]
   Plasma levels of cholesterol (total cholesterol, LDL-cholesterol and HDL-cholesterol) measured at baseline and after 4 weeks intervention (and as a "control measurement" at the screening visit)
3. Lipid profile- Apolipoproteins [ Time Frame: 4 weeks ]
   Plasma levels of apolipoproteins (apoB and apoA) measured at baseline and after 4 weeks intervention (and as a "control measurement" at the screening visit)
4. Lipid profile- Lipoproteins [ Time Frame: 4 weeks ]
   Plasma levels of Lp(a) and lipoprotein subclasses measured at baseline and after 4 weeks intervention (and as a "control measurement" at the screening visit)
5. Inflammatory markers [ Time Frame: 4 weeks ]
   The concentration of circulating levels of inflammatory markers measured at baseline and after 4 weeks intervention ( and as a "control measurement" at screening)
6. Gene expression [ Time Frame: 4 weeks ]
   Changes in PBMC (peripheral blood mononuclear cell) gene expression profile measured at baseline and after 4 week of intervention
7. Pain sensitivity [ Time Frame: 4 weeks ]
   Measured by cold pressure tests at baseline and after 4 week of intervention ( and as a control measurement at screening)
8. Resolvins [ Time Frame: 4 weeks ]
   Blood levels of resolvins (omega- 3 derivates) concentrations measured at baseline and after 4 week of intervention ( and as a control measurement at screening)
9. Metabolome [ Time Frame: 4 weeks ]
   Changes in metabolome measured at baseline and after 4 week of intervention

Eligibility Criteria

• Ages Eligible for Study: 20 Years to 70 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• BMI 20-35kg/m2
• opportunity to meet for 3 visits at the Department of Nutrition, University of Oslo, during the study period.

Exclusion Criteria:

• Chronic disease (liver/kidney/metabolism)
• Alcohol overconsumption (>40g/day)
• Diabetes and high fasting blood glucose
• Pregnant/ breastfeeding or planning pregnancy during the study period
• High fish intake (>3 meals/week).
• Blood donation during the study period
• Difficulty following the study protocol.
• Smoking/snuffing
• Regularly use of anti-inflammatory drugs
• Regularly use of omega-3 supplements /cod liver oil.

Contacts and Locations

Locations

Norway

University of Oslo

Oslo, Norway, 0316

Sponsors and Collaborators

University of Oslo

Oslo University Hospital

More Information

• Responsible Party: Kirsten Holven, Professor, University of Oslo
• ClinicalTrials.gov Identifier: NCT04841044
• Other Study ID Numbers: REK 176979
• First Posted: April 12, 2021
• Last Update Posted: October 4, 2021
• Last Verified: September 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: Data will not be sheared as individual participant data, but the results will be shared on group levels. All participants information are treated deidentified

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Kirsten Holven, University of Oslo:

Omega 3 fatty acids; Sustainability; Cetoleic acid; Very long monounsaturated fatty acid; Cardiovascular disease prevention; Antiinflammation